Opioid-related Fatalities Research Articles

Opioid-related overdose deaths among people experiencing homelessness, 2017 to 2021: A population-based analysis using coroner and health administrative data from Ontario, Canada

ObjectiveWe aimed to measure the change in proportion of opioid-related overdose deaths attributed to people experiencing homelessness and to compare the opioid-related fatalities between individuals experiencing homelessness and not experiencing homelessness at time of death. ApproachWe conducted a population-based, time-trend analysis using coroner and health administrative databases from Ontario, Canada (2017-2021). Quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness were reported. We also obtained socio-demographic and health characteristics, healthcare encounters preceding death, substances directly contributing to death and circumstances surrounding deaths. ResultsOverall, 13.3% individuals who died of an opioid-related overdose between 2017 and 2021 were identified as experiencing homelessness at the time of death. The quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness increased from 7.2% in 2017 to 16.8% by 2021. Compared with housed decedents, those experiencing homelessness were younger, had higher prevalence of mental health or substance use disorders and more often visited hospitals and emergency departments in the year prior to death. Fentanyl and stimulants more often directly contributed to death, whereas methadone was less often present. Individuals experiencing homelessness were more often in the presence of a bystander during the event that led to death and more often had a resuscitation attempted or naloxone administered. Conclusions and implicationsPeople experiencing homelessness account for an increasing proportion of fatal opioid-related overdoses in Ontario, Canada, reaching nearly one in six such deaths in 2021. Effective interventions are needed to combat homelessness and opioid related toxicity in homeless populations.

Improving Engagement in Residential Treatment for Substance Use Disorders: An Integrated Care Quality Improvement Project for Individuals With Mental Health and Substance Use Disorders

Substance use disorder continues to pose significant challenges in the United States, with increasing opioid-related fatalities. Residential recovery treatment programs are effective; however, high attrition rates impact successful long-term outcomes. This quality improvement project aimed to enhance patient engagement in treatment for mental health and substance use disorder to improve retention rates. It also implemented an integrated care approach incorporating psychotherapy, psychopharmacologic interventions, and recovery support services. The project was conducted using a 2-group predesign and postdesign, analyzing 134 admissions. The approach resulted in a statistically significant increase in patient engagement in treatment from 24% to 92%. Substance use relapse rates significantly reduced from 25% to 12%, and a clinically meaningful increase in the 3-month retention rate was noted. Integrated care is a promising strategy to improve outcomes for individuals receiving care for co-occurring disorders via residential treatment settings. Future studies should explore integrative models of care, patient motivation, and retention in residential treatment centers.

Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development.

The opioid crisis in the United States is a significant public health issue, with a nearly threefold increase in opioid-related fatalities between 1999 and 2014. In response to this crisis, society has made numerous efforts to mitigate its impact. Recent advancements in understanding the structural intricacies of the κ opioid receptor (KOR) have improved our knowledge of how opioids interact with their receptors, triggering downstream signaling pathways that lead to pain relief. This review concentrates on the KOR, offering crucial structural insights into the binding mechanisms of both agonists and antagonists to the receptor. Through comparative analysis of the atomic details of the binding site, distinct interactions specific to agonists and antagonists have been identified. These insights not only enhance our understanding of ligand binding mechanisms but also shed light on potential pathways for developing new opioid analgesics with an improved risk-benefit profile.

Drug Stigma, Consumer Culture, and Corporate Power in the Opioid Crisis

Recent efforts to rethink drug-related stigma have been increasingly considering the power dimension of the concept, to show how stigma formations flow top-down from governments, as well as other political or corporate stakeholders, towards the powerless and marginalised. Stigma attaches itself to the individual and collective identities of the substance-using subject. But it equally alters the multiple lives of the substance. In the US opioid crisis of recent decades, big pharma companies could be seen lobbying the medical profession and harnessing their power to destigmatise opioid painkillers, as part of wider marketing and sales strategies. This has been subsequently linked with rising opioid-related fatalities and spiralling harms among some of the most vulnerable groups. This theoretical paper locates the object-stigma of drugs between the cultural confines of ‘limbic capitalism’ (the drive to seek pleasure and meaning through consumption) and ‘palliative capitalism’ (the drive to pathologise and medicate ills attributed to the individual, but not the system). It argues that stigma should be viewed as a dynamic force which, under the guise of consumer culture and the veil of scientific rationality, can be manipulated by business elites to shift meanings around pain, pleasure, and addiction, in ways that are potentially conducive to social harms.

A novel preclinical model of fentanyl-induced cardiorespiratory collapse to investigate resuscitation outcomes

Introduction: Opioid-related morbidities have become a critical public health concern, with ultrapotent synthetic opioids (UPSO) such as fentanyl contributing to the rise in opioid-related fatalities. Respiratory depression is the cardinal trait of fentanyl overdose, leading to systemic hypoxia and subsequent cardiorespiratory collapse (CRC). There is growing recognition that fentanyl induced CRC (fiCRC) is unique from other forms of sudden CRC. Yet, the consequences of fiCRC and its reversal remain poorly understood. This is due in part to the limited preclinical studies investigating rescue from fiCRC. Objective: using a novel model of fiCRC and subsequent reversal, this ongoing study aims to define the impact of UPSO and naloxone rescue on in vivo survival outcomes. Methods and Results: Male and female C57BL/6J mice were used. UPSO fentanyl i.v. administration (30 to 500 mcg/kg) suppressed breathing and subsequently led to fiCRC. The return of spontaneous circulation (ROSC) was achieved by performing manual chest compressions in combination of epinephrine administration after 8 minutes of fiCRC. In subset of mice, naloxone was administered post ROSC. Outcomes after 72 hours were accessed. The latency of fiCRC (mean arterial pressure at 40 mmHg) exhibited a negative correlation with the doses of fentanyl administered. Resuscitation from fiCRC was unreliable across the dose spectrum, while naloxone consistently rescued the majority of fiCRC animals. Naloxone increased ROSC rate from 54% to 86% when the dose of fentanyl was 30 mcg/Kg (n=22). With naloxone rescue, we compared fiCRC with non-opioid-induced cardiac arrest followed by potassium chloride injection (0.8 mg/g). Both models showed severe lung edema as evidenced by Evans Blue staining. However, the lung wet/dry weight ratio was higher in fiCRC group than in the non-opioid treatment group (5.50±0.05 vs. 6.60±0.60, n=4, p<0.05). Survival in fiCRC group was significantly worse than in non-opioid treatment group (survival rate: 25% vs. 83%, n=17, p<0.05). Conclusions: Our study highlights two important findings. First, the reliable resuscitation of fiCRC necessitates the use of naloxone. Second, the likelihood of injury is significant following successful rescue from fiCRC by naloxone. Our continued work using this fiCRC model will lead to insights that can be leveraged for strategies to mitigate injury and improve survival following fentanyl overdose. R01 HL163965 & R01 DA057767. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Opioid abuse, the escalating crisis, xylazine co-use, and the forensic toxicology challenges

Introduction: The opioid crisis represents a longstanding public health emergency, significantly worsened by the concurrent use of xylazine. This epidemic has led to a surge in opioid-related fatalities, marking it as a pressing health crisis with global implications. The combination of xylazine with fentanyl and its analogs significantly increases the risk of overdose deaths. This study aims to analyze the current situation by reviewing scientific and governmental publications on the topic. Methods: Our analysis, established on data from PubMed, Google Scholar, and Scopus, highlights the pharmacological risks related to the combination of xylazine and synthetic opioids, such as fentanyl. It underlines the increased chances of fatal overdoses due to this combination. Results: The research associates weaknesses in current forensic toxicology screenings that fail to effectively detect these dangerous compounds. The illegal synthesis of these substances is a key challenge in directing the emergency. The combination of xylazine with synthetic opioids shows a significant public health risk, worsening the already critical opioid crisis. There is a critical need for improved drug detection and analysis methods to combat this growing challenge. Conclusion: Developing forensic toxicology screenings to precisely identify the presence of these substances is crucial for both the diagnosis and prevention of fatal overdoses. Our findings emphasize the requirement for immediate and concerted efforts to address the complexities of the opioid epidemic and highlight the potential consequences of public health strategies intended to mitigate this crisis.

Provider perceptions of systems-level barriers and facilitators to utilizing family-based treatment approaches in adolescent and young adult opioid use disorder treatment

BackgroundAmidst increasing opioid-related fatalities in adolescents and young adults (AYA), there is an urgent need to enhance the quality and availability of developmentally appropriate, evidence-based treatments for opioid use disorder (OUD) and improve youth engagement in treatment. Involving families in treatment planning and therapy augments medication-based OUD treatment for AYA by increasing treatment engagement and retention. Yet, uptake of family-involved treatment for OUD remains low. This study examined systems-level barriers and facilitators to integrating families in AYA OUD treatment in Rhode Island.MethodsAn online survey was administered to clinic leaders and direct care providers who work with AYA in programs that provide medication and psychosocial treatments for OUD. The survey assessed attitudes towards and experiences with family-based treatment, barriers and facilitators to family-based treatment utilization, as well as other available treatment services for AYA and family members. Findings were summarized using descriptive statistics.ResultsA total of 104 respondents from 14 distinct treatment programs completed the survey. Most identified as White (72.5%), female (72.7%), and between 25 and 44 years of age (59.4%). Over half (54.1%) of respondents reported no experience with family based treatment and limited current opportunities to involve families. Barriers perceived as most impactful to adopting family-based treatment were related to limited available resources (i.e. for staff training, program expansion) and lack of prioritization of family-based treatment in staff productivity requirements. Barriers perceived as least impactful were respondent beliefs and attitudes about family-based treatment (e.g., perception of the evidence strength and quality of family-based treatment, interest in implementing family-based treatment) as well as leadership support of family-based treatment approaches. Respondents identified several other gaps in availability of comprehensive treatment services, especially for adolescents (e.g. services that increase social recovery capital).ConclusionsFamily-based treatment opportunities for AYA with OUD in Rhode Island are limited. Affordable and accessible training programs are needed to increase provider familiarity and competency with family-based treatment. Implementation of programming to increase family involvement in treatment (i.e. psychoeducational and skills-based groups for family members) rather than adopting a family-based treatment model may be a more feasible step to better meet the needs of AYA with OUD.Trial registration: not applicable.

Reducing the Likelihood of Opioid Overdose Fatalities on College and University Campuses: An Action Plan and Model.

For more than two decades there has been a continuous rise in opioid overdose related deaths. The majority of the deaths include the age range when, traditionally, individuals are likely to attend college or university. As a result, Vassar College has taken the important initiative and created and implemented a new opioid overdose intervention strategy and action plan called AED+. AED+ expands on the Model of Greater Awareness, Training and Increased Availability of and Accessibility to Life Saving Intervention Devices; a model that was created based on AED devices improving outcomes of out-of-hospital cardiac arrest emergencies. Similar to AED's improving out-of-hospital cardiac arrest outcomes, the + component of the AED+ initiative increases awareness and provides basic, targeted education about naloxone and its use. Furthermore, the education includes information about naloxone's greater availability and its more immediate access across the campus by students, staff, faculty, administrators, and visitors in the event of a suspected opioid overdose. Starting in May 2023, members of the school's Health Service and senior administrative leaders identified it necessary to be proactive and not reactive to managing an opioid overdose in the campus community. Although Vassar College has not recently experienced an opioid overdose, it is confidently projected that these targeted actions will proactively and positively reduce the likelihood of opioid-related fatalities on campus. Furthermore, it is the purpose of this article to share the AED+ model so other colleges and universities can modify it to best fit their unique setting in order to improve opioid overdose outcomes.

Distribution of intranasal naloxone to potential opioid overdose bystanders in Sweden: effects on overdose mortality in a full region-wide study

ObjectivesDistribution of take-home naloxone is suggested to reduce opioid-related fatalities, but few studies have examined the effects on overdose deaths in the general population of an entire community. This study...

Pain Management Throughout Pediatric Laparoscopic Appendectomy: A Systematic Review.

Opioid-related fatalities are a leading cause of accidental death in the United States. Appendicitis is a common cause of abdominal pain in children and adolescents. The management of pain throughout the laparoscopic appendectomy (LA) in the pediatric population is a critical concern. This study aimed to evaluate trends in analgesic use and patient satisfaction following LA, with a focus on reducing the reliance on opioids for pain management. From 2003 to 2023, 18258 articles were filtered for all types of analgesic use with LA. The publications were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 19 studies were included for analysis and review. The study included peer-reviewed experimental and observational studies involving individuals under 18 years. Pain management strategies varied across studies, involving a combination of analgesics, nerve blocks, and wound infiltrations. Analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids were administered before and after surgery. Some studies implemented patient-controlled analgesia (PCA) pumps. Other studies explored non-pharmacological interventions like magnetic acupuncture. The results showed a reduction in the need for postoperative analgesics in patients treated with LA, particularly when using non-opioid medications and novel analgesic techniques. Pediatric patients who received gabapentin reported lower opioid use, shorter hospital stays, and high satisfaction rates. However, the reliance on opioids remained significant in some cases, particularly among patients with peritonitis who required more morphine. Pain management in pediatric patients is multifaceted, involving preoperative and postoperative analgesics, nerve blocks, and PCA pumps. Efforts to improve pain management following pediatric LA while reducing opioid reliance are essential in the context of the ongoing opioid epidemic. The findings from this study highlight the potential benefits of non-opioid analgesics, nerve blocks, and alternative methods for managing postoperative pain in <18 appendectomy patients. Further research and standardization of pain management protocols are needed to ensure optimal patient outcomes and minimize the risk of opioid-related complications.

Opioid-related overdose deaths among people experiencing homelessness, 2017 to 2021: A population-based analysis using coroner and health administrative data from Ontario, Canada.

To measure the change in proportion of opioid-related overdose deaths attributed to people experiencing homelessness and to compare the opioid-related fatalities between individuals experiencing homelessness and not experiencing homelessness at time of death. Population-based, time-trend analysis using coroner and health administrative databases from Ontario, Canada from 1 July 2017 and 30 June 2021. Quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness. We also obtained socio-demographic and health characteristics of decedents, health-care encounters preceding death, substances directly contributing to death and circumstances surrounding deaths. A total of 6644 individuals (median age = 40 years, interquartile range = 31-51; 74.1% male) experienced an accidental opioid-related overdose death, among whom 884 (13.3%) were identified as experiencing homelessness at the time of death. The quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness increased from 7.2% (26/359) in July-September 2017 to 16.8% (97/578) by April-June 2021 (trend test P < 0.01). Compared with housed decedents, those experiencing homelessness were younger (61.3 versus 53.1% aged 25-44), had higher prevalence of mental health or substance use disorders (77.1 versus 67.1%) and more often visited hospitals (32.1 versus 24.5%) and emergency departments (82.6 versus 68.5%) in the year prior to death. Fentanyl and its analogues more often directly contributed to death among people experiencing homelessness (94.0 versus 81.4%), as did stimulants (67.4 versus 51.6%); in contrast, methadone was less often present (7.8 versus 12.4%). Individuals experiencing homelessness were more often in the presence of a bystander during the acute toxicity event that led to death (55.8 versus 49.7%); and where another individual was present, more often had a resuscitation attempted (61.7 versus 55.1%) or naloxone administered (41.2 versus 28.9%). People experiencing homelessness account for an increasing proportion of fatal opioid-related overdoses in Ontario, Canada, reaching nearly one in six such deaths in 2021.

Opioid Analgesics after Bariatric Surgery: A Scoping Review to Evaluate Physiological Risk Factors for Opioid-Related Harm.

The persisting use of opioids following bariatric surgery has emerged as a prevalent complication, heightening the probability of opioid-related harm (ORM), such as opioid-related fatalities and prescription opioid use disorder (OUD). A comprehensive review of PubMed literature from 1990 to 2023 was conducted to pinpoint physiological influences on postoperative ORM. As a result, we found that patients undertaking bariatric operations often exhibit an inherently higher risk for substance use disorders, likely attributable to genetic predisposition and related neurobiological changes that engender obesity and addiction-like tendencies. Furthermore, chronic pain is a common post-bariatric surgery complaint, and the surgical type impacts opioid needs, with increased long-term opioid use after surgeries. Additionally, the subjective nature of pain perception in patients with obesity can distort pain reporting and the corresponding opioid prescription both before and after surgery. Furthermore, the postoperative alterations to the gastrointestinal structure can affect the microbiome and opioid absorption rates, resulting in fluctuating systemic exposure to orally ingested opioids. The prospect of ORM development post-bariatric surgery appears amplified due to a preexisting susceptibility to addictive habits, surgically induced pain, modified gut-brain interaction and pain management and the changed pharmacokinetics post-surgery. Further research is warranted to clarify these potential risk variables for ORM, specifically OUD, in the bariatric population.

Geospatial Analysis of Opioid Dispensing Patterns in California: A 2021 Real-World Study.

The misuse and abuse of opioids has become a serious public health threat in the United States. The state of California has been hit particularly hard by the opioid epidemic, with a noticeable increase in opioid-related fatalities and hospitalizations. This brief report paper aims to contribute to the growing literature by conducting a geospatial analysis of opioid dispensing patterns in California in 2021. The primary objective was to identify areas characterized by high-risk opioid dispending patterns and explore possible contributing factors. This retrospective study analyzed data from over 7 million records of opioid and benzodiazepine prescriptions dispensed by outpatient pharmacies in California in 2021. A series of generalized linear regression models was employed to assess the impact of neighborhood characteristics on opioid recipients and high-risk opioid dispensing. The study defined high-risk opioid dispensing behavior as: (1) multiple provider episodes, (2) overlapping opioid prescriptions for seven or more days, (3) overlapping opioid and benzodiazepine prescriptions for seven or more days, and (4) a high standardized dosage of opioid prescriptions per month. The study identified variables associated with high-risk opioid dispensing behaviors, including age, population density, income, and housing-related variables, as well as marital status and family-related variables. The study uncovered that there are noticeable disparities in opioid dispensing among different racial and ethnic groups within California. The findings indicated a correlation of high-risk dispensing indicators with certain demographic and socioeconomic factors. There was a substantial regional variation in opioid dispensing practices, with certain rural areas having higher rates of opioid prescriptions than urban areas.

Opioids Now Account for More Than Half of Child Poisoning Deaths

Study finds dramatic increase in opioid-related fatalities.

National Analysis of Motor Vehicle Collision-Associated Mortality Among Opioid Users From 2010 to 2020: The Need for Effective Prevention Policies.

The purpose of this study is to evaluate the trends in the incidence of opioid-associated motor vehicle fatalities in the United States (US) over the past decade and identify geographic or demographic trends. We conducted a retrospective repeated cross-sectional study utilizing the CDC WONDER Multiple Cause of Death Database to gather data on opioid-associated motor vehicle fatalities from 2010 to 2020. The southern US experienced the highest percent increase in opioid-related fatalities from 2010 to 2020 (263.1%), followed by the Midwest (160.7%), the west (86.3%), and the northeast (10.0%). The use of opioids increases a driver's risk of motor vehicle crash involvement, especially amongst non-Hispanic White males between 25 and 55years of age who live in the southern states of the US. There is a need for augmented opioid-related policy concerning the potency and intake of prescription opioids to reduce motor vehicle fatalities.

Fatal and nonfatal opioid overdose risk following release from prison: A retrospective cohort study using linked administrative data

IntroductionAmong individuals who are released from prison, opioid overdose is a leading cause of death with a risk more than ten-fold the general population. Although the epidemiology of opioid-related fatalities has been described, few studies have characterized both fatal and nonfatal opioid-related poisonings. The objective of this study was to estimate risk of fatal and nonfatal opioid overdose among adults released from prison. MethodsThe study estimated fatal and nonfatal opioid overdose rates using linked corrections, Medicaid, hospital discharge, and vital statistics from the state of Oregon from 2014 to 2018. Multivariable proportional hazards models identified demographic and prison-related factors associated with overdose. ResultsBetween 2014 and 2017, 18,258 individuals were released from prison. A majority of individuals were male (87 %) and ages 26 to 64 (83 %). Two-thirds had a documented substance use disorder treatment need and 20 % demonstrated mental health treatment need. Following prison release, 579 opioid overdose events occurred; 65 (11 %) were fatal. The rate of opioid overdose was 1085.7 per 100,000 person-years (PY). Rates were highest in the first two weeks (2286.7 per 100,000 PY), among women (1582.9 per 100,000 PY), and those with mental health (1624.3 per 100,000 PY) or substance use disorder treatment needs (1382.6 per 100,100 PY). Only mental health (adjusted hazard ratio [aHR] 1.54, 95 % CI 1.24 to 1.90) and substance use need (aHR 2.59; 95 % CI 2.01 to 3.34) remained significant in multivariable models. ConclusionsThe rate of opioid overdose is markedly elevated after prison release, particularly in the first two weeks. In women, the higher rate of opioid overdose is mediated by a greater mental health burden.

Structurally diverse fentanyl analogs yield differential locomotor activities in mice

Synthetic narcotics have been implicated as the single greatest contributor to increases in opioid-related fatalities in recent years. This study evaluated the effects of nine fentanyl-related substances that have emerged in the recreational drug marketplace, and for which there are no existing or only limited in vivo data. Adult male Swiss Webster mice were administered fentanyl-related substances and their effects on locomotion as compared to MOR agonist standards were recorded. In locomotor activity tests, morphine (100, 180 mg/kg), buprenorphine (1, 10 mg/kg), fentanyl (1, 10 mg/kg), cyclopropylfentanyl (1, 10 mg/kg), cyclopentylfentanyl (10 mg/kg), (±)-cis-3-methylbutyrylfentanyl (0.1, 1, 10 mg/kg), ortho-methylacetylfentanyl (10 mg/kg), para-chloroisobutyrylfentanyl (100 mg/kg), ocfentanil (1, 10 mg/kg), and ortho-fluoroacrylfentanyl (0.1, 1, 10 mg/kg) elicited significant (p ≤ 0.05) dose-dependent increases in locomotion. However, 2,2,3,3-tetramethylcyclopropylfentanyl did not have any effects on locomotion, even when tested up to 100 mg/kg, and 4′-methylacetylfentanyl (10, 100 mg/kg) significantly decreased locomotion. The rank order of efficacy for stimulating locomotion (maximum effect as a % of fentanyl's maximum effect) for fentanyl-related substances relative to MOR agonist standards was cyclopropylfentanyl (108.84 ± 20.21) > fentanyl (100 ± 15.3) > ocfentanil (79.27 ± 16.92) > morphine (75.9 ± 14.5) > (±)-cis-3-methylbutyrylfentanyl (68.04 ± 10.08) > ortho-fluoroacrylfentanyl (63.56 ± 19.88) > cyclopentylfentanyl (56.46 ± 8.54) > para-chloroisobutyrylfentanyl (22.44 ± 8.51) > buprenorphine (11.26 ± 2.30) > ortho-methylacetylfentanyl (9.45 ± 2.92) > 2,2,3,3-tetramethylcyclopropylfentanyl (6.75 ± 1.43) > 4′-methylacetylfentanyl (3.47 ± 0.43). These findings extend in vivo results from previous reports documenting additional fentanyl related-related substances that stimulate locomotion similar to known abused opioids while also identifying some anomalies.

Oxytocin and orexin systems bidirectionally regulate the ability of opioid cues to bias reward seeking

As opioid-related fatalities continue to rise, the need for novel opioid use disorder (OUD) treatments could not be more urgent. Two separate hypothalamic neuropeptide systems have shown promise in preclinical OUD models. The oxytocin system, originating in the paraventricular nucleus (PVN), may protect against OUD severity. By contrast, the orexin system, originating in the lateral hypothalamus (LH), may exacerbate OUD severity. Thus, activating the oxytocin system or inhibiting the orexin system are potential therapeutic strategies. The specific role of these systems with regard to specific OUD outcomes, however, is not fully understood. Here, we probed the therapeutic efficacy of pharmacological interventions targeting the orexin or oxytocin system on two distinct metrics of OUD severity in rats—heroin choice (versus choice for natural reward, i.e., food) and cued reward seeking. Using a preclinical model that generates approximately equal choice between heroin and food reward, we examined the impact of exogenously administered oxytocin, an oxytocin receptor antagonist (L-368,899), and a dual orexin receptor antagonist (DORA-12) on opioid choice. Whereas these agents did not alter heroin choice when rewards (heroin and food) were available, oxytocin and DORA-12 each significantly reduced heroin seeking in the presence of competing reward cues when no rewards were available. In addition, the number of LH orexin neurons and PVN oxytocin neurons correlated with specific behavioral economic variables indicative of heroin versus food motivation. These data identify a novel bidirectional role of the oxytocin and orexin systems in the ability of opioid-related cues to bias reward seeking.

Women-Reported Barriers and Facilitators of Continued Engagement with Medications for Opioid Use Disorder.

Opioid-related fatalities increased exponentially during the COVID-19 pandemic and show little sign of abating. Despite decades of scientific evidence that sustained engagement with medications for opioid use disorders (MOUD) yields positive psychosocial outcomes, less than 30% of people with OUD engage in MOUD. Treatment rates are lowest for women. The aim of this project was to identify women-specific barriers and facilitators to treatment engagement, drawing from the lived experience of women in treatment. Data are provided from a parent study that used a community-partnered participatory research approach to adapt an evidence-based digital storytelling intervention for supporting continued MOUD treatment engagement. The parent study collected qualitative data between August and December 2018 from 20 women in Western Massachusetts who had received MOUD for at least 90 days. Using constructivist grounded theory, we identified major themes and selected illustrative quotations. Key barriers identified in this project include: (1) MOUD-specific discrimination encountered via social media, and in workplace and treatment/recovery settings; and (2) fear, perceptions, and experiences with MOUD, including mental health medication synergies, internalization of MOUD-related stigma, expectations of treatment duration, and opioid-specific mistrust of providers. Women identified two key facilitators to MOUD engagement: (1) feeling “safe” within treatment settings and (2) online communities as a source of positive reinforcement. We conclude with women-specific recommendations for research and interventions to improve MOUD engagement and provide human-centered care for this historically marginalized population.

Effect of sustained high buprenorphine plasma concentrations on fentanyl-induced respiratory depression: A placebo-controlled crossover study in healthy volunteers and opioid-tolerant patients.

BackgroundOpioid-induced respiratory depression driven by ligand binding to mu-opioid receptors is a leading cause of opioid-related fatalities. Buprenorphine, a partial agonist, binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects. The authors examined whether sustained buprenorphine plasma concentrations similar to those achieved with some extended-release injections used to treat opioid use disorder could reduce the frequency and magnitude of fentanyl-induced respiratory depression.MethodsIn this two-period crossover, single-centre study, 14 healthy volunteers (single-blind, randomized) and eight opioid-tolerant patients taking daily opioid doses ≥90 mg oral morphine equivalents (open-label) received continuous intravenous buprenorphine or placebo for 360 minutes, targeting buprenorphine plasma concentrations of 0.2 or 0.5 ng/mL in healthy volunteers and 1.0, 2.0 or 5.0 ng/mL in opioid-tolerant patients. Upon reaching target concentrations, participants received up to four escalating intravenous doses of fentanyl. The primary endpoint was change in isohypercapnic minute ventilation (VE). Additionally, occurrence of apnea was recorded.ResultsFentanyl-induced changes in VE were smaller at higher buprenorphine plasma concentrations. In healthy volunteers, at target buprenorphine concentration of 0.5 ng/mL, the first and second fentanyl boluses reduced VE by [LSmean (95% CI)] 26% (13–40%) and 47% (37–59%) compared to 51% (38–64%) and 79% (69–89%) during placebo infusion (p = 0.001 and < .001, respectively). Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection. In opioid-tolerant patients, fentanyl reduced VE up to 49% (21–76%) during buprenorphine infusion (all concentration groups combined) versus up to 100% (68–132%) during placebo infusion (p = 0.006). In opioid-tolerant patients, the risk of experiencing apnea requiring verbal stimulation following fentanyl boluses was lower with buprenorphine than with placebo (odds ratio: 0.07; 95% CI: 0.0 to 0.3; p = 0.001).InterpretationResults from this proof-of-principle study provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids like fentanyl.