Total-body imaging of mu-opioid receptors with [11C]carfentanil in non-human primates.

PURPOSE: Mu-opioid receptors (MORs) are widely expressed in the central nervous system (CNS), peripheral organs, and immune system. This study measured the whole body distribution of MORs in rhesus macaques using the MOR selective radioligand [11C]carfentanil ([11C]CFN) on the PennPET Explorer. Both baseline and blocking studies were conducted using either naloxone or GSK1521498 to measure the effect of the antagonists on MOR binding in both CNS and peripheral organs. METHODS: The PennPET Explorer was used for MOR total-body PET imaging in four rhesus macaques using [11C]CFN under baseline, naloxone pretreatment, and naloxone or GSK1521498 displacement conditions. Logan distribution volume ratio (DVR) was calculated by using a reference model to quantitate brain regions, and the standard uptake value ratios (SUVRs) were calculated for peripheral organs. The percent receptor occupancy (%RO) was calculated to establish the blocking effect of 0.14 mg/kg naloxone or GSK1521498. RESULTS: The %RO in MOR-abundant brain regions was 75-90% for naloxone and 72-84% for GSK1521498 in blocking studies. A higher than 90% of %RO were observed in cervical spinal cord for both naloxone and GSK1521498. It took approximately 4-6 min for naloxone or GSK1521498 to distribute to CNS and displace [11C]CFN from the MOR. A smaller effect was observed in heart wall in the naloxone and GSK1521498 blocking studies. CONCLUSION: [11C]CFN total-body PET scans could be a useful approach for studying mechanism of action of MOR drugs used in the treatment of acute and chronic opioid use disorder and their effect on the biodistribution of synthetic opioids such as CFN. GSK1521498 could be a potential naloxone alternative to reverse opioid overdose.

The optimization of harm reduction services in Massachusetts through the use of GIS: Location-allocation analyses, 2019-2021.

BACKGROUND: Fatal opioid-related overdoses (OOD) continue to be a leading cause of preventable death across the US. Opioid Overdose Education and Naloxone Distribution programs (OENDs) play a vital role in addressing morbidity and mortality associated with opioid use, but access to such services is often inequitable. We utilized a geographic information system (GIS) and spatial analytical methods to inform prioritized placement of OEND services in Massachusetts. METHODS: We obtained addresses for OEND sites from the Massachusetts Department of Public Health and address-level fatal OOD data for January 2019 to December 2021 from the Massachusetts Registry of Vital Records and Statistics. Using location-allocation approaches in ArcGIS Pro, we created p-median models using locations of existing OEND sites and fatal OOD counts to identify areas that should be prioritized for future OEND placement. Variables included in our analysis were transportation mode, distance from public schools, race and ethnicity, and location feasibility. RESULTS: Three Massachusetts communities - Athol, Dorchester, and Fitchburg - were identified as priority sites for new OEND locations using location-allocation models based on capacity to maximize OOD prevention. Communities identified by the models for OEND placement had similar demographics and overdose rates (42.8 per 100,000 vs 40.1 per 100,000 population) to communities with existing OEND programs but lower naloxone kit distribution rates (2589 doses per 100,000 vs 3704 doses per 100,000). Further models demonstrated differential access based on location and transportation. CONCLUSION: Our analyses identified key areas of Massachusetts with greatest need for OEND services. Further, these results demonstrate the utility of using spatial epidemiological methods to inform public health recommendations.

Reducing perceived barriers to scaling up overdose education and naloxone distribution and medications for opioid use disorder in the United States in the HEALing (Helping End Addiction Long-Term®) communities study.

BACKGROUND: Scaling up overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD) is needed to reduce opioid overdose deaths, but barriers are pervasive. This study examines whether the Communities That HEAL (CTH) intervention reduced perceived barriers to expanding OEND and MOUD in healthcare/behavioral health, criminal-legal, and other/non-traditional venues. METHODS: The HEALing (Helping End Addiction Long-Term®) Communities Study is a parallel, wait-list, cluster randomized trial testing the CTH intervention in 67 communities in the United States. Surveys administered to coalition members and key stakeholders measured the magnitude of perceived barriers to scaling up OEND and MOUD in November 2019-January 2020, May-June 2021, and May-June 2022. Multilevel linear mixed models compared Wave 1 (intervention) and Wave 2 (wait-list control) respondents. Interactions by rural/urban status and research site were tested. RESULTS: Wave 1 respondents reported significantly greater reductions in mean scores for three outcomes: perceived barriers to scaling up OEND in Healthcare/Behavioral Health Venues (-0.26, 95% confidence interval, CI: -0.48, -0.05, p = 0.015), OEND in Other/Non-traditional Venues (-0.53, 95% CI: - 0.84, -0.22, p = 0.001) and MOUD in Other/Non-traditional Venues (-0.34, 95% CI: -0.62, -0.05, p = 0.020). There were significant interactions by research site for perceived barriers to scaling up OEND and MOUD in Criminal-Legal Venues. There were no significant interactions by rural/urban status. DISCUSSION: The CTH Intervention reduced perceived barriers to scaling up OEND and MOUD in certain venues, with no difference in effectiveness between rural and urban communities. More research is needed to understand facilitators and barriers in different venues.

Neighborhood and Individual Disparities in Community-Based Naloxone Access for Opioid Overdose Prevention.

Improving access to naloxone for laypersons is a cornerstone of the US strategy to reduce opioid overdose deaths. This study evaluated change in distance to opioid overdose prevention programs (OOPPs) providing walk-in naloxone across two time points. We also explored individual and neighborhood disparities in distance to OOPPs, associations between 2020 OOPP locations and 2018 overdoses, and associations between OOPPs and neighborhood fatal overdose rates. Using fatal opioid overdose locations in 2018 (n = 1167) and 2020 (n = 2045) in New York City, we mapped OOPP locations and fatal overdose locations to visualize areas of unmet naloxone need. We used logistic regression to assess individual (age, sex, race/ethnicity) and neighborhood correlates of odds of an overdose occurring within walking distance (≤ 0.5 miles or 0.8 km) of an OOPP and negative binomial regression to assess the relationship between census tract-level OOPP counts and overdose rates. Distance to OOPPs significantly improved over time, with average distance decreasing by 1.7 miles (2.7 km) (p < 0.001). OOPPs were more likely to be located in neighborhoods with higher poverty in both years and in closer proximity to Latinos in 2020-suggesting improved access for Latinos and in higher poverty neighborhoods. OOPP locations in 2020 were significantly positively associated with overdose locations in 2018. OOPPs were not well-situated in neighborhoods with elevated overdose rates in 2018 but were better situated in 2020, controlling for other neighborhood variables. Community lay naloxone access through OOPPs improved over time and could have promising effects for improved overdose rates in the future.

A new pharmacological approach for tracheal intubation?

Anaesthesia induced with remimazolam and a fentanyl-series opioid can be reversed with flumazenil and naloxone. Concomitant paralysis with rocuronium can facilitate tracheal intubation whilst being reversible with sugammadex. Together, this combination might offer full reversibility of a 'routine' or a 'rapid-sequence' induction anaesthesia. Whether this is useful, or even safe, requires careful evaluation.

PBPK-PD model for predicting morphine pharmacokinetics, CNS effects and naloxone antagonism in humans.

Morphine and morphine-6-glucuronide (M6G) produce central nervous system (CNS) effects by activating mu-opioid receptors, while naloxone is used mainly for the reversal of opioid overdose, specifically for the fatal complication of respiratory depression, but also for alleviating opioid-induced side effects. In this study we developed a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to simultaneously predict pharmacokinetics and CNS effects (miosis, respiratory depression and analgesia) of morphine as well as antagonistic effects of naloxone against morphine. The pharmacokinetic and pharmacodynamic parameters were obtained from in vitro data, in silico, or animals. Pharmacokinetic and pharmacodynamic simulations were conducted using 39 and 36 clinical reports, respectively. The pharmacokinetics of morphine and M6G following oral or intravenous administration were simulated, and the PBPK-PD model was validated using clinical observations. The Emax model correlated CNS effects with free concentrations of morphine and M6G in brain parenchyma. The predicted CNS effects were compared with observations. Most clinical observations fell within the 5th-95th percentiles of simulations based on 1000 virtual individuals. Most of the simulated area under the concentration-time curve or peak concentrations also fell within 0.5-2-fold of observations. The contribution of morphine to CNS effects following intravenous or oral administration was larger than that of M6G. Pharmacokinetics and antagonistic effects of naloxone on CNS effects were also successfully predicted using the developed PBPK-PD model. In conclusion, the pharmacokinetics and pharmacodynamics of morphine and M6G, antagonistic effects of naloxone against morphine-induced CNS effects may be successfully predicted using the developed PBPK-PD model based on the parameters derived from in vitro, in silico, or animal studies.

Comparative evaluation of craving, sleep quality, sexual function and quality of life in opioid use disorder patients in remission with buprenorphine/naloxone maintenance treatment.

AIM: To compare opioid use disorder (OUD) patients who continue to use opioids and are in remission with buprenorphine-naloxone (B/N) in terms of some parameters and to evaluate the relationship between B/N dose and these parameters. METHOD: We included 141 OUD patients in remission with B/N maintenance treatment for at least 6 months, 141 who still used opioids, and 141 healthy volunteers. Substance Craving Scale (SCS), Pittsburgh Sleep Quality Index (PSQI), Arizona Sexual Experiences Scale (ASEX), and Short Form 36 (SF-36) were administered. RESULTS: PSQI scores and ASEX scores were higher in those who continued to use opiates than in OUD in remission, and in OUD in remission compared to controls. OUD patients with current opioid use also had lower SF-36 scores compared to both patients in remission and healthy controls. SCS, PSQI, ASEX, and SF-36 scores were similar when the three groups were examined based on the dosage of B/N (below 8, 8-15, and 16 mg/day and above) use in OUD in remission. CONCLUSIONS: Quality of life, craving, sleep and sexual functions improved significantly with B/N; however, these effects are not dependent on B/N dosage.

The Association Between Self-Reported Anxiety and Retention in Opioid Agonist Therapy: Findings From a Canadian Pragmatic Trial.

BACKGROUND: Prescription-type opioid use disorder (POUD) is often accompanied by comorbid anxiety, yet the impact of anxiety on retention in opioid agonist therapy (OAT) is unclear. Therefore, this study investigated whether baseline anxiety severity affects retention in OAT and whether this effect differs by OAT type (methadone maintenance therapy (MMT) vs. buprenorphine/naloxone (BNX)). METHODS: This secondary analysis used data from a pan-Canadian randomized trial comparing flexible take-home dosing BNX and standard supervised MMT for 24 weeks. The study included 268 adults with POUD. Baseline anxiety was assessed using the Beck Anxiety Inventory (BAI), with BAI ≥ 16 indicating moderate-to-severe anxiety. The primary outcomes were retention in assigned and any OAT at week 24. In addition, the impact of anxiety severity on retention was examined, and assigned OAT was considered an effect modifier. RESULTS: Of the participants, 176 (65%) reported moderate-to-severe baseline anxiety. In adjusted analyses, there was no significant difference in retention between those with BAI ≥ 16 and those with BAI < 16 assigned (29% vs. 28%; odds ratio (OR) = 2.03, 95% confidence interval (CI) = 0.94-4.40; P = 0.07) or any OAT (35% vs. 34%; OR = 1.57, 95% CI = 0.77-3.21; P = 0.21). In addition, there was no significant effect modification by OAT type for retention in assigned (P = 0.41) or any OAT (P = 0.71). In adjusted analyses, greater retention in treatment was associated with BNX (vs. MMT), male gender identity (vs. female, transgender, or other), enrolment in the Quebec study site (vs. other sites), and absence of a positive urine drug screen for stimulants at baseline. CONCLUSIONS: Baseline anxiety severity did not significantly impact retention in OAT for adults with POUD, and there was no significant effect modification by OAT type. However, the overall retention rates were low, highlighting the need to develop new strategies to minimize the risk of attrition from treatment. CLINICAL TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (NCT03033732).

Patients presenting to the ED with nonfatal drug overdose: Self-reported history of overdose and naloxone use.

BACKGROUND: In the context of polysubstance use and fentanyl detection in non-opioid drugs supplies (e.g., cocaine, methamphetamine), it is important to re-evaluate and expand our understanding of which populations are at high risk for fatal drug overdoses. The primary objective of this pilot study was to gather data from the ED to characterize the population presenting with drug overdose, including demographics, drug use patterns and comorbidities, to inform upstream overdose prevention efforts. METHODS: A consecutive sample of ED patients undergoing treatment for non-fatal overdose were prospectively recruited for study participation at the time of ED visit. Participants reported history of substance use over the past six months, recent and lifetime overdose, and naloxone receipt and administration history. RESULTS: A total of 76 eligible participants were enrolled over the course of seven months. Participants reported high rates of opioid (56%), stimulant (56%), and cannabis use (59%). Self-reported polysubstance use, defined as self-reported use of more than one substance, was 83%. Of enrolled participants, 64% reported at least one overdose and 39% reported three or more lifetime overdoses prior to their index overdose ED visit. Participants with no self-reported intentional opioid use (n = 32) in the past six months had fentanyl positive urine drug screen 84% of the time versus 89% in the overall study population (n = 74). Participants who did not report opioid use in the past six months were less likely to possess (34% vs. 55%) or to know how to acquire (50% vs. 74%) naloxone compared to participants with self-reported history of opioid use. CONCLUSION: This study demonstrated high rates of fentanyl exposure on toxicology testing at time of overdose across all participants including study participants without self-reported intentional opioid use. Data gathered in the ED at time of overdose can be used to inform upstream naloxone distribution and public health initiatives.

How Ohio public library systems respond to opioid-related substance use: a descriptive analysis of survey results.

BACKGROUND: Public libraries in the United States have experienced increases in opioid-related substance use in their communities and on their premises. This includes fatal and non-fatal overdose events. Some libraries have adopted response measures in their branches to deter substance use or prevent overdose. A small number of libraries around the nation have decided to stock the opioid antagonist naloxone (Narcan) for staff to administer to patrons who experience overdose. This response measure has generated extensive media attention. Although Ohio ranks fourth in age-adjusted drug mortality rate in the United States, there has been no investigation of whether Ohio libraries are observing opioid-related transactions, consumption, and/or overdose events, or which measures they have adopted in response to these activities. We conducted a multimethod survey with Ohio public library directors to identify the response measures they have adopted. We present descriptive findings from the quantitative and qualitative items in our survey. METHODS: We conducted a cross-sectional 54-item multimethod survey of public library system directors (one per system) in Ohio. Directors of each of Ohio's public library systems were invited to participate via email. RESULTS: Of 251 library systems, 56 responded (22.3% response rate), with 34 respondents (60.7%) indicating awareness of opioid-related transactions, consumption, and/or overdose on their premises. Most (n = 43, 76.8%) did not stock naloxone in their buildings. Over half (n = 34, 60.7%) reported implementing one or more non-naloxone response measures. These measures focus on improving security for staff and patrons, deterring opioid-related transactions (purchases and exchanges) and consumption, and providing educational events on substance use. Nearly half (n = 25, 47.2%) partner with community organizations to provide opioid response measures. A similar proportion reported adequate funding to respond to opioid-related substance use (n = 23, 45.1%), and most (n = 38, 74.5%) reported adequate support from their boards and communities. Few respondents have implemented evaluations of their response measures. CONCLUSIONS: Ohio public libraries are responding to evidence of opioid-related transactions, consumption, and/or overdose on their premises with a range of measures that focus on substance use prevention and deterrence. Most Ohio library systems do not stock naloxone. Respondents indicated they prefer to call 911 and let first responders handle overdose events. The majority of respondents indicated their library systems have political capacity to respond to evidence of opioid-related substance use on their premises, but have limited operational and functional capacity. Findings suggest the need to revisit assumptions that public libraries are willing to stock naloxone to respond to overdose events, and that libraries have the resources to respond robustly to opioid-related transactions, consumption, and/or overdose on their premises.

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial.

BACKGROUND: Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. METHODS: Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h- 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. RESULTS: Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. CONCLUSION: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg- 1. h- 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

Possible unusual presentation of opioid side effect in a child: a case report.

Atypical presentations are commonly encountered in the Pediatric intensive care unit (PICU) but having a high index of suspicion is crucial to prevent or treat severe and life-threatening conditions. This case describes the clinical presentation and course of a 14-month-old girl with congenital heart disease who was admitted to the PICU after cardiac repair and remained agitated, irritable, in hysteria and delirium despite adequate sedation. Different measures to relieve her condition were attempted but to no avail. All the common causes of this atypical presentation including pain, ventilator induced agitation, low cardiac output syndrome (LCOS), opioid side effects, toxicity, opioid induced neurotoxicity (OIN) as well as withdrawal syndrome were ruled out. However, the use of naloxone as a last resort after exhausting all the other options has led to immediate and successful reversal of her symptoms.

Intrauterine exposure to maternal opioid maintenance treatment and associated risk factors may impair child growth.

AIM: How maternal opioid maintenance treatment (OMT) affects children is under-researched. This population-based registry study investigated child growth and somatic health following intrauterine exposure to this treatment. METHODS: Children born between 1 March 2011 and 30 May 2021 to mothers who used buprenorphine, buprenorphine-naloxone, or methadone throughout their pregnancies were followed for 2 years at the Helsinki University Hospital, Finland. Appropriate statistical tests were used to compare the treatment groups. RESULTS: Of the 67 neonates, 52% were male, 96% were born full-term and 63% were treated for neonatal opioid withdrawal syndrome. Otherwise, the children were predominantly healthy, although relatively small: 22% were small for gestational age, the methadone group children being the smallest. Foetal exposure to maternal methadone treatment, illicit drugs, hepatitis C and smoking were associated with small for gestational age; the former two were also associated with later slower growth, especially head growth and weight gain (p < 0.001). However, 29% were overweight at 2 years. CONCLUSION: Using child growth as the outcome, we found that buprenorphine-naloxone and buprenorphine-monotherapy had equal effects as forms of maternal OMT. Exposure to multiple risk factors may harm foetal and subsequent growth. We recommend long-term follow-up of children exposed to maternal OMT.

Healthcare provider perspectives on emergency department-initiated buprenorphine/naloxone: a qualitative study.

BACKGROUND: Take-home buprenorphine/naloxone is an effective method of initiating opioid agonist therapy in the Emergency Department (ED) that requires ED healthcare worker buy-in for large-scale implementation. We aimed to investigate healthcare workers perceptions of ED take-home buprenorphine/naloxone, as well as barriers and facilitators from an ED healthcare worker perspective. METHODS: In the context of a take-home buprenorphine/naloxone feasibility study at a tertiary care teaching hospital we conducted a descriptive qualitative study. We conducted one-on-one in person or telephone interviews and focus groups with ED healthcare workers who cared for patients given take-home buprenorphine/naloxone in the feasibility study at Vancouver General Hospital from July 2019 to March 2020. We conducted 37 healthcare worker interviews from December 2019 to July 2020. We audio recorded interviews and focus groups and transcribed them verbatim. We completed interviews until we reached thematic saturation. DATA ANALYSIS: We inductively coded a sample of transcripts to generate a provisional coding structure and to identify emerging themes, which were reviewed by our multidisciplinary team. We then used the final coding structure to analyze the transcripts. We present our findings descriptively. RESULTS: Participants identified a number of context-specific facilitators and barriers to take-home buprenorphine/naloxone provision in the ED. Participants highlighted ED conditions having either facilitative or prohibitive effects: provision of buprenorphine/naloxone was feasible when ED volume was low and space was available but became less so as ED volume increased and space decreased. Similarly, participants noted that patient-related factors could have a facilitative or prohibitive effect, such as willingness to wait (willing to stay in the ED for study-related activities and buprenorphine/naloxone initiation activities), receptiveness to buprenorphine/naloxone, and comprehension of the instructions. As for staff-related factors, time was identified as a consistent barrier. Time included time available and time required to initiate buprenorphine/naloxone (including time building rapport). Healthcare worker familiarity with buprenorphine/naloxone was noted as either a facilitating factor or a barrier, and healthcare workers indicated that ongoing training would have been advantageous. Many healthcare workers identified that the ED is an important first point of contact for the target patient population. CONCLUSION: Integrating a buprenorphine/naloxone program into ED care requires organizational supports (e.g., for managing buprenorphine/naloxone within limitations of ED volume, space, and time), and ongoing education of healthcare workers to minimize identified barriers.

Naloxone Knowledge and Attitudes Towards Overdose Response Among Family Members of People who Misuse Opioids.

Providing family members of individuals with opioid use disorders (OUD) naloxone is a cost-effective way to prevent overdose deaths. However, misconceptions and negative attitudes towards naloxone hinder family engagement with naloxone programs. This study examines factors associated with knowledge and attitudes toward naloxone among adults with close family members who misused opioids. Adults with family members (parent, step-parent, child, spouse, sibling, or step-sibling) who misused opioids (N = 299) completed a web-based survey. Participants were recruited through treatment providers, community groups, and social media. Surveys assessed naloxone knowledge, attitudes toward overdose response, demographics, completion of naloxone training, attitude toward medications for OUD, and family members' overdose history. Multiple regression was used to identify factors associated with naloxone knowledge (Model 1) and attitudes toward overdose response (Model 2). A graduate degree (B = .35, p < .003) and a history of overdose (B = 0.21, p = .032) were associated with greater naloxone knowledge. Age (B = .11, p < .001), race/ethnicity (B = -1.39, p = .037), naloxone training (B = 2.70, p < .001), and more positive attitude toward medications for OUD (B = 1.50, p = .003) were associated with attitudes toward overdose response. Family members are potential allies in reducing drug overdose deaths, and families may need broader education about naloxone. Awareness of previous overdose was associated with greater naloxone knowledge. Findings related to race/ethnicity suggest the need to reach family members of minoritized racial groups to provide access to naloxone training. Findings point to where education and distribution efforts may focus on increasing knowledge and improving attitudes among those closest to people with OUD.

Access to, Experience with, and Attitudes towards Take Home Naloxone: An Online Survey.

The opioid public health crisis continues to burden individuals, communities, and economies. Public health opinion has emphasized the need for increased access to harm reduction services, but there is a dearth of information on the views and experiences of people who use opioids. Our study aimed to investigate the prevalence of naloxone use, attitudes, and experiences with naloxone among an online community of people who use drugs. We performed a cross-sectional survey looking at experiences with and attitudes towards take-home naloxone. Data is presented descriptively, with analysis of the differences between people who do and do not use opioids using the χ2 and Fisher's exact tests. There were 1,143 respondents, of whom 70% were from the United States. Only 38% of participants who use opioids had received naloxone training, but 56% of these individuals said that they felt comfortable using a naloxone kit. Nearly all respondents (95%) said they would be willing to use naloxone on someone who had overdosed and approximately 90% would want naloxone used on them in case of an overdose. Regarding harm reduction, 24% of respondents said they had access to safe use programs, and 33% said they had access to clean needle exchange programs. A majority of the participants who use opioids were in favor of having naloxone with them when using drugs and believed naloxone should be freely available. This study demonstrates the receptiveness of take-home naloxone and highlights the need for better implementation of naloxone within communities that use opioids.

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.

G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists.

The ability of a ligand to preferentially promote engagement of one signaling pathway over another downstream of GPCR activation has been referred to as signaling bias, functional selectivity, and biased agonism. The presentation of ligand bias reflects selectivity between active states of the receptor, which may result in the display of preferential engagement with one signaling pathway over another. In this study, we provide evidence that the G protein-biased mu opioid receptor (MOR) agonists SR-17018 and SR-14968 stabilize the MOR in a wash-resistant yet antagonist-reversible G protein-signaling state. Furthermore, we demonstrate that these structurally related biased agonists are noncompetitive for radiolabeled MOR antagonist binding, and while they stimulate G protein signaling in mouse brains, partial agonists of this class do not compete with full agonist activation. Importantly, opioid antagonists can readily reverse their effects in vivo. Given that chronic treatment with SR-17018 does not lead to tolerance in several mouse pain models, this feature may be desirable for the development of long-lasting opioid analgesics that remain sensitive to antagonist reversal of respiratory suppression.

Adolescent morphine exposure changes the endogenous vlPAG opioid response to inflammatory pain in rats.

Adolescence is one of the most critical periods for brain development, and exposure to morphine during this period can have long-life effects on pain-related behaviors. The opioid system in the periaqueductal gray (PAG) is highly vulnerable to drug exposure. However, the impact of adolescent morphine exposure (AME) on the endogenous opioid system in the PAG is currently unknown. This study aims to investigate the long-lasting effects of AME on the endogenous opioid system and its involvement in altering nociceptive behaviors. Adolescent rats were given escalating doses of morphine (2.5-25 mg/kg, subcutaneous) or an equal volume of saline twice daily for 10 consecutive days (PND 31-40). After a 30-day washout period, adult rats underwent formalin tests following microinjection of morphine, naloxone, or saline into the ventrolateral PAG (vlPAG) region. The results indicated that morphine microinjection into the vlPAG of the adolescent morphine-treated group significantly reduced the nociceptive score. However, the analgesic response to morphine in this group was significantly lower compared to the saline-treated group during adolescence. Additionally, the nociceptive score significantly increased following naloxone but not saline microinjection into the vlPAG of the saline-treated group during adolescence, rather than the morphine-treated one. These findings indicate that AME has long-lasting effects on the endogenous opioid system in the vlPAG, which can consequently alter behaviors related to inflammatory pain in adulthood.

Missouri's Overdose Field Report: descriptive analysis, survival trends, and naloxone dosing patterns from a community-based survey tool, 2018-2022.

Background: Missouri's Overdose Field Report (ODFR) is a community-based reporting system which intends to capture overdoses which may not be otherwise recorded.Objectives: Describe the factors related to non-fatal overdoses reported to Missouri's ODFR.Methods: This study used a descriptive epidemiological approach to examine the demographics and circumstances of overdoses reported to the ODFR. We used binary logistic regression to evaluate factors associated with survival and ordinal logistic regression to evaluate factors associated with number of doses used. Factors were chosen based on their relevance to overdose education and survival, and naloxone distribution.Results: Between 2018 and 2022, 12,225 overdoses (67% male; 78% White) were reported through the ODFR, with a 96% (n = 11,225) survival rate. Overdose survival (ps < .02) was associated with younger age (OR = .58), no opioid and stimulant co-involvement (OR = .61), and private location (OR = .48). Intramuscular naloxone in particular was associated with a significantly higher odds of survival compared to nasal naloxone (OR = 2.11). An average of 1.6 doses of naloxone per incident were administered. Additional doses were associated (ps < .02) with being older (OR = .45), female (OR = .90), nasal naloxone (versus intravenous) (OR = .65), and the belief fentanyl was present (OR = 1.49).Conclusion: Our reporting form provides a comprehensive picture of the events surrounding reported overdoses, including factors associated with survival, how much naloxone was used, and the effects of respondents believing fentanyl was involved. Missouri's report can provide support for current naloxone dosing, contextualize refusing post-overdose transport, and can be used to improve overdose response by community and first responders.