Direct analysis in real time mass spectrometry (DART-MS/MS) for rapid urine opioid detection in a clinical setting.

BACKGROUND AND AIMS: Current laboratory methods for opioid detection involve an initial screening with immunoassays which offers efficient but non-specific results and a subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmation which offers accurate results but requires extensive sample preparation and turnaround time. Direct Analysis in Real Time (DART) tandem mass spectrometry is evaluated as an alternative approach for accurate opioid detection with efficient sample preparation and turnaround time. MATERIALS AND METHODS: DART-MS/MS was optimized by testing the method with varying temperatures, operation modes, extraction methods, hydrolysis times, and vortex times. The method was evaluated for 12 opioids by testing the analytical measurement range, percent carryover, precision studies, stability, and method-to-method comparison with LC-MS/MS. RESULTS: DART-MS/MS shows high sensitivity and specificity for the detection of 6-acetylmorphine, codeine, hydromorphone, oxymorphone, hydrocodone, naloxone, buprenorphine, norfentanyl, and fentanyl in urine samples. However, its performance was suboptimal for norbuprenorphine, morphine and oxycodone. CONCLUSION: In this proof-of-concept study, DART-MS/MS is evaluated for its rapid quantitative definitive testing of opioids drugs in urine. Further research is needed to expand its application to other areas of drug testing.

The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines.

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

Opioid Use Disorder and intracerebral hemorrhage in Isfahan, Iran: a case-control study.

Background: Opium use disorder is a significant health problem in our country, leading to a considerable number of health issues. Opium has several detrimental effects on its consumers. However, the effect of Opium use disorder on intracerebral hemorrhage (ICH) has not been evaluated. This study aims to evaluate the relationship between Opium use disorder and ICH. Methods: In this case-control study, 402 patients with ICH and 404 patients without ICH enrolled. Opium use disorder, other vascular risk factors including diabetes mellitus, hypertension, hyperlipidemia, and tobacco smoking was compared between these groups. Patients with ICH were divided into two groups; first group are patients with history of Opioid Use Disorder and second group are those patients without Opioid Use Disorder. ICH features including clinical and imaging characteristics and prognostic findings were compared between patients with and without Opium use disorder. Results: This case-control study of 806 participants found that hypertension (OR = 6.84, 95% CI: 5.03-9.34, p-value: <0.001), Opium use disorder (OR = 4.23, 95% CI: 2.42-7.35, p-value: <0.001) and tobacco smoking (OR = 1.47, 95% CI: 1.01-2.16, p-value: 0.049) had a higher risk of ICH. Opium-addicted subjects had higher ICH scores (2.61 ± 1.27 vs. 2.11 ± 1.29, p-value: 0.005), were more likely to have infratentorial hemorrhage (22% vs. 12%, OR = 2.13, 95% CI: 1.06-4.28, p-value: 0.038), more likely to be intubated (66% vs. 54%, OR = 1.79, 95% CI: 0.98-3.27, p-value = 0.041) and had lower GCS scores (9.58 ± 3.60 vs. 8.25 ± 3.88, p-value: 0.01). The effect of Opium use disorder independently on ICH was also shown in logistic regression (adjusted OR = 3.15, p-value = 0.001). Conclusion: This study is the first to evaluate the effect of Opium use disorder on ICH, identifying Opium use disorder as a new potential risk factor for ICH.

Ongoing Opioid Treatment and Symptoms of Myocardial Infarction in Calls to the Emergency Medical Services.

Background: Ongoing opioid treatment can potentially modify symptoms of myocardial infarction (MI) and cause a lack of recognition and treatment delay. Objectives: The purpose of this study was to examine MI symptoms and the time to hospitalization for patients in ongoing opioid treatment compared to patients without ongoing opioid treatment. Methods: We evaluated calls to the Copenhagen Emergency Medical Services in Denmark from 2014 to 2018. Calls were included when followed by hospitalization and a diagnosis of MI. Symptoms of MI and the time from call to hospitalization in patients in ongoing opioid treatment initiated prior to the onset of MI were compared to a control group of MI patients without opioid treatment. Results: In total, 6,633 calls were included; 552 calls from patients in opioid treatment and 6,081 calls from controls. Patients in opioid treatment were older and had more comorbidities than controls. Chest pain was less prevalent in MI patients in opioid treatment compared to controls (adjOR: 0.70; 95% CI: 0.57-0.85). The median time from the call to hospitalization was longer in patients in opioid treatment than in controls (50 vs 47 minutes; P = 0.006). Conclusions: In calls to the Emergency Medical Services, opioid treatment initiated prior to the onset of MI was associated with less frequent chest pain in MI. Therefore, awareness of ongoing opioid treatment may improve telephone triage of patients with MI, as symptom presentation in opioid-treated patients may differ and potentially challenge and delay the emergency response.

Nerve Blocks for Post-Surgical Pain Management: A Narrative Review of Current Research.

Opioids remain the mainstay of post-surgical pain management; however, concerns regarding addiction and side effects necessitate the exploration of alternatives. This narrative review highlights the potential of nerve blocks as a safe and effective strategy for post-surgical pain control. This review explores the use of various nerve block techniques tailored to specific surgical procedures. These include nerve blocks for abdominal surgeries; fascial plane blocks for chest surgeries; nerve blocks for arm surgeries; and nerve blocks for lower limb surgery including; femoral, hip, and knee surgeries. By targeting specific nerves, these blocks can provide targeted pain relief without the negative side effects associated with opioids. Emerging evidence suggests that nerve blocks can be as effective as opioids in managing pain, while potentially offering additional benefits such as faster recovery, improved patient satisfaction, and reduced reliance on opioids. However, the effectiveness of nerve blocks varies depending on type of surgery, and in individual patients. Rebound pain, which temporary increase in pain after a block wears off, can occur. In addition, some techniques require specialized guidance for accurate placement. In conclusion, nerve blocks show great promise as effective alternatives for managing post-surgical pain. They can reduce the need for opioids and their side effects, leading to better patient outcomes and satisfaction. Future studies should assess the long-term impacts of specific nerve blocks on mortality rates, cost-effectiveness, and their incorporation into multimodal pain management approaches to further enhance post-surgical care.

Repurposing prescribed hydromorphone: Alternative uses of safer supply and tablet-injectable opioid agonist treatment to meet unaddressed health needs.

BACKGROUND: In response to the ongoing overdose crisis in Canada, a number of opioid agonist treatment and safer supply programs provide people at high overdose risk with daily-dispensed tablet hydromorphone, with some requiring witnessed ingestion and others providing take-away doses. While these programs are intended to reduce overdose events by limiting people's use of the contaminated drug supply, the experiences of people receiving hydromorphone vary. In this article we explore the ways people repurpose hydromorphone to address unmet needs. METHODS: This article draws on in-depth qualitative interviews from two studies evaluating hydromorphone tablet distribution programs in British Columbia, Canada. We used thematic analysis to identify themes related to repurposing hydromorphone. We compared themes across the two studies to identify any similarities or differences in relation to the ways study participants discussed repurposing hydromorphone tablets. We utilize vignettes - snapshots of participant experiences - to analyse and represent the data. RESULTS: Four vignettes demonstrate how hydromorphone tablets are often being used to address and resolve unmet needs of people who use drugs. While most participants reported reducing their use of illicit drugs, a variety of instrumental uses of tablet hydromorphone were also discussed, including reducing anxiety, addressing sleep issues, withdrawal management, and managing chronic pain. CONCLUSION: Our findings demonstrate how people who use drugs are maximizing the benefits of tablet hydromorphone distribution to address unmet needs. Hydromorphone distribution programs represent a public health and harm reduction intervention that is usefully addressing experiences related to structural vulnerabilities (such as inadequate pain management), which are often overlooked amongst stigmatized groups.

Opioid Prescribing Trends Among Workers' Compensation Patients Undergoing Foot and Ankle Surgery.

BACKGROUND: The purpose of this study was to evaluate opioid usage and prescribing trends among workers' compensation (WC) patients who underwent foot or ankle operative procedures compared with a control group. METHODS: A retrospective review was conducted for WC and non-WC patients who underwent foot or ankle procedures in a single academic orthopaedic surgery practice. Outcome measures were total morphine milligram equivalents (MME) and number of opioid prescriptions. RESULTS: A total of 118 patients were identified, including 51 patients in the WC group and 67 in the non-WC group. After index surgery, 67% (34 of 51) of WC patients had 2 or more additional opioid prescriptions compared to 39% (26 of 67) of non-WC patients (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.4-6.7; P = .003). Collectively, there were greater prescriptions of oxycodone MME (P = .002) and hydrocodone MME (P = .07) in the WC cohort. CONCLUSIONS: Workers' compensation patients seem to be prescribed and consume opioids at a higher rate postoperatively. It is important for treating physicians to be aware of these trends, and discussions with patients regarding expected opioid use when planning surgical intervention may be beneficial. Physicians may need to set expectations preoperatively and suggest there are limits on the amount of opioids that can safely be prescribed. LEVEL OF EVIDENCE: Level III, Retrospective cohort study, Prognostic.

Examining use of telehealth in jails: linking women to community OUD services.

BACKGROUND: Opioid use disorder (OUD) remains a significant health care need for women, particularly those involved in the criminal legal system (CLS). There are no studies to date that focus on the utilization of telehealth as a platform for assessment and linkage to medications to treat opioid use disorder (MOUD) at community re-entry for women, despite the fact that women have unique risk factors that may contribute to opioid relapse in the community. The purpose of this mixed-methods study is to provide an overview of the innovative use of telehealth for linking incarcerated women to community MOUD treatment in the Kentucky-hub of the Justice Community Opioid Innovation Network (JCOIN). METHODS: This study incorporates qualitative and quantitative data collection with MOUD providers, recovery staff involved in peer navigation services, and women who are incarcerated to understand perceptions of the use of telehealth prior to jail release as a linkage to community services. RESULTS: Findings from this study suggest overall support for the use of telehealth between community MOUD treatment providers and women who are incarcerated using videoconferencing technology. On average, there was very little variation in provider favorable feedback related to clinical engagement or in face-to-face comparability, as well as how telehealth allowed the participant to discuss personal and sensitive issues during the clinical assessment. CONCLUSIONS: Study findings suggest benefits associated with the use of telehealth in increasing access to treatment for women with OUD. Jails are critical venues for telehealth interventions because they provide the opportunity to reach women who have been actively using illicit substances, often have advanced-stage substance use disorders which have compromised their health and mental health, and often have not been previously identified as needing treatment. TRIAL REGISTRATION: This study was originally registered on 8/23/19, ClinicalTrials.gov, #NCT04069624.

Association Between Rapid Opioid Reduction or Discontinuation and Self-Harm, Suicide Attempt, and Suicide Death Among High-Dose Long-Term Opioid Therapy Patients in North Carolina, 2006-2018.

We examined the association between rapid opioid reduction or discontinuation and self-harm, suicide attempt, and suicide death among high-dose long-term opioid therapy (HD-LTOT) patient and examined effect measure modification by individual and neighborhood-level characteristics. Using private insurance data from North Carolina, this retrospective cohort study covered January 2006 to September 2018, with up to four years of follow-up. Participants included patients aged 18-64 years who were prescribed HD-LTOT. Time-varying exposure was ever exposed to rapid opioid reduction or discontinuation vs never exposed. The outcomes were self-harm or suicide attempt, suicide death, and the combined outcome. We estimated cumulative incidence and used Fine-Gray models to estimate sub-distribution hazard ratios (HRs). There were 21,450 HD-LTOT patients. In year 1, rapid opioid reduction or discontinuation was not associated with the combined outcome, HR: 1.09 (95% CI: 0.61-1.96). However, in years 2-4, rapid opioid reduction or discontinuation was associated with higher hazard of the combined outcome, HR: 2.77 (95% CI: 1.45-5.27). This association was stronger among patients with mental health conditions and those residing in underserved neighborhoods. These findings underscore the importance of provider training in adhering to guideline-concordant gradual tapering, offering mental health support, and ensuring patient safety throughout the tapering process.

Facilitators of and barriers to buprenorphine initiation in the emergency department: a scoping review.

Buprenorphine initiation in the Emergency Department (ED) has been hailed as an evidence-based strategy to mitigate the opioid overdose crisis, but its implementation has been limited. This scoping review synthesizes barriers and facilitators to buprenorphine initiation in the ED, and uses the Consolidated Framework for Implementation Research and a critical lens to analyze the literature. Results demonstrate an immense effort across the U.S. and Canada to implement ED-initiated buprenorphine. Facilitators include multidisciplinary addiction teams and co-located, low-barrier, harm reduction-informed services to support transitions. Barriers include a failure to address structural stigma, client complexity, and an increasingly toxic drug supply. The literature also misses the opportunity to include the perspectives of service users, health administrators, and learners. Increased coordination of implementation efforts, and a shift to equitable and inclusive opioid agonist therapy initiation pathways are needed across the U.S. and Canada.

Systematic Review on Mortality in the Elderly on Methadone Maintenance Treatment.

Opioid dependence is a serious public health concern, particularly for older individuals who have a high prevalence of comorbid conditions. To effectively manage opioid use disorder (OUD), methadone maintenance treatment (MMT) is crucial; however, the MMT poses certain challenges for the aging population. The purpose of this review is to evaluate the impact of MMT on health outcomes, identify predictive factors for mortality, and assess mortality rates among older individuals receiving MMT. A systematic search was performed across databases, including PubMed, Scopus, Web of Science, and Google Scholar, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies included were published between January 2000 and December 2023, focused on elderly patients (60 years of age and older) receiving MMT and provided information on death rates. A total of 15 studies were examined. The main causes of death for older MMT patients were overdose, respiratory issues, and cardiovascular diseases. The annual mortality rates for these patients ranged from 2% to 10%. Treatment outcomes and mortality were significantly impacted by comorbid conditions. Greater treatment adherence and longer care periods were observed in older individuals, which correlated with better health outcomes and lower mortality. This review makes clear how elderly MMT patients with addiction and chronic health issues require integrated care models. Treatment effectiveness may be further increased by gender-specific interventions. For this aging population, policy reforms and enhanced healthcare support are essential. To enhance clinical results and lower mortality rates among older individuals enrolled in MMT programs, comprehensive age-appropriate care models are crucial. Long-term health outcomes should be investigated further and evidence-based treatments for older individuals with OUD should be developed.

Managing Cancer Pain in Hospitalized Patients with Comorbid Opioid Use Disorder with Buprenorphine: A Case Series.

Data indicate that one in five patients with cancer might be at risk for nonmedical opioid use and its extreme form, opioid use disorder (OUD). Buprenorphine is one of the few medications available for the management of patients with co-occurring OUD and chronic pain. Care for these patients can be challenging and require the expertise of specialist clinicians with a deep understanding of addiction and cancer pain. Regrettably, these specialist clinicians may not always be available and accessible when patients are admitted to the hospital. Reports on how primary non-specialist clinicians without access to specialist addiction services navigate the care of such patients in the inpatient setting are limited. We hereby describe the care of three patients with OUD receiving buprenorphine who were hospitalized for cancer pain.

Buprenorphine use among non-hospital residential programs.

BACKGROUND: The purpose of this study is to investigate the use of buprenorphine within non-hospital residential programs. We hypothesize that programs offering long-term treatment will be less likely to accept or prescribe buprenorphine, but those that accept public insurance will demonstrate relative increased likelihood of buprenorphine availability. METHOD: This study analyzed data from the 2021 National Substance Use and Mental Health Services Survey. The analytic sample (n=3654) included a subset of facilities that reported providing only substance use treatment, including three non-mutually exclusive service types: detox, short-term, and long-term. A logistic regression examined the association between buprenorphine availability and residential service type, holding constant characteristics associated with the outcome of interest. We then tested an interaction between public insurance and long-term service type on the outcome of interest. RESULTS: While long-term service type was associated with reduced odds of buprenorphine availability (OR=.288, p <.05), programs that both offered long-term residential programs and accepted public health insurance had 3.5 higher odds of accepting or prescribing buprenorphine (OR=4.586, p<.01) compared to long-term programs without public insurance. IMPLICATIONS: Patients who require treatment of longer duration may face barriers to buprenorphine availability; however, public insurance acceptance may increase odds of availability of buprenorphine among long-term programs.

Integrative Review of Opioid Use and Protocol Adherence in Hospitals After Implementing Enhanced Recovery After Surgery Protocols for Cesarean Birth.

OBJECTIVE: To evaluate the enhanced recovery after surgery (ERAS) protocols used and amount of opioids administered during hospitalization for cesarean birth after the ERAS protocols were implemented. DATA SOURCES: A search was conducted in CINAHL Complete, Scopus, and PubMed for sources published in English between January 2018 and December 2023. Search terms were cesarean AND opioid∗ AND eras OR erac OR enhanced recovery. STUDY SELECTION: Eligible studies were conducted in the United States, used key pain management components from the ERAS guidelines, and reported results for in-patient postsurgical opioid use. DATA EXTRACTION: Data obtained were for post-ERAS implementation only and included authors, date, sample size, study location, participant inclusion and exclusion criteria, methods, interventions used (ERAS guideline components), and morphine milligram equivalents used during the hospital stay. DATA SYNTHESIS: Weighted averages were calculated for results reported as means and percentages. Descriptive summaries were used for the remainder of the results. RESULTS: Twenty-six studies were found, accounting for 19,961 individuals' experiences after ERAS implementation. Although 30% of participants experienced only scheduled cesarean births, 70% experienced all types of cesarean births, including scheduled, urgent, or emergent. There was substantial heterogeneity of the data reported, especially for opioid use and time frames. In 11 studies that reported means, the weighted average for opioid use was 54 morphine milligram equivalents per stay. In 17 studies, researchers reported the number of women who experienced an opioid-free recovery, which averaged 40% of the women. CONCLUSION: Implementation of standardized orders built on the ERAS guidelines in U.S. hospitals is associated with reduced opioid exposure for women experiencing scheduled and nonscheduled cesarean births while maintaining adequate pain relief. This review offers evidence that can support perinatal teams who are considering ERAS for cesarean birth or those looking for further improvements.

Provider costs of treating opioid dependence with extended-release buprenorphine in Australia.

INTRODUCTION: The costs of providing medication-assisted treatment for opioid dependence can determine its scale of provision. To provide estimates of the costs of extended-release buprenorphine (BUP-XR), we performed a bottom-up costing analysis of provider operational treatment costs. METHODS: Data were collected in a single-arm open label trial of BUP-XR injections conducted in specialist public drug treatment services and primary care private practices in three Australian states (the CoLAB study). The unit costs of resources used for each activity were combined with quantities used at each participating facility to arrive at the average annual cost per client. RESULTS: One hundred participants across the six health facility sites received monthly subcutaneous BUP-XR injections administered by a health-care practitioner. The average cost of providing 1 year of treatment per participant was $6656 ($6026-$8326). Screening cost (initial assessment and medical history) was $282 while monthly follow-up appointments cost $531 per client. The main cost driver was the monthly treatment costs accounting for 79% of the average annual client cost, with medication costs comprising 95% of this cost. DISCUSSION AND CONCLUSION: With medication costs making up the largest proportion of treatment costs, treatment using BUP-XR has the potential to free up other health system resources, for example, staff time. The costs reported in this study can be used in an economic evaluation to estimate the net benefit or cost-effectiveness of BUP-XR especially when compared to other opioid agonist treatments.

Kappa-opioid receptor blockade in the inferior colliculus of prey threatened by pit vipers decreases anxiety and panic-like behaviour.

The dorsal midbrain comprises dorsal columns of the periaqueductal grey matter and corpora quadrigemina. These structures are rich in beta-endorphinergic and leu-enkephalinergic neurons and receive GABAergic inputs from substantia nigra pars reticulata. Although the inferior colliculus (IC) is mainly involved in the acoustic pathways, the electrical and chemical stimulation of central and pericentral nuclei of the IC elicits a vigorous defensive behaviour. The defensive immobility and escape elicited by IC activation is commonly related to panic-like emotional states. To investigate the role of κ-opioid receptor of the IC in the antiaversive effects of endogenous opioid receptor blockade in a dangerous situation, male Wistar rats were pretreated in the IC with the κ-opioid receptor-selective antagonist nor-binaltorphimine at different concentrations and submitted to the non-enriched polygonal arena for a snake panic test in the presence of a rattlesnake and, after 24 h, prey were resubmitted to the experimental context. The snakes elicited in prey a set of antipredatory behaviours, such as the anxiety-like responses of defensive attention and risk assessment, and the panic-like reactions of defensive immobility and either escape or active avoidance during the elaboration of unconditioned and conditioned fear-related responses. Pretreatment of the IC with microinjections of nor-binaltorphimine at higher concentrations significantly decreased the frequency and duration of both anxiety- and panic-attack-like behaviours. These findings suggest that κ-opioid receptor blockade in the IC causes anxiolytic- and panicolytic-like responses in threatening conditions, and that kappa-opioid receptor-selective antagonists can be a putative coadjutant treatment for panic syndrome treatment.

In vitro and in vivo study of butyrylfentanyl and 4-fluorobutyrylfentanyl in female and male mice: Role of the CRF1 receptor in cardiorespiratory impairment.

BACKGROUND AND PURPOSE: Fentanyl analogues have been implicated in many cases of intoxication and death with overdose worldwide. The aim of this study is to investigate the pharmaco-toxicology of two fentanyl analogues: butyrylfentanyl (BUF) and 4-fluorobutyrylfentanyl (4F-BUF). EXPERIMENTAL APPROACH: In vitro, we measured agonist opioid receptor efficacy, potency, and selectivity and ability to promote interaction of the µ receptor with G protein and ß-arrestin 2. In vivo, we evaluated thermal antinociception, stimulated motor activity and cardiorespiratory changes in female and male CD-1 mice injected with BUF or 4F-BUF (0.1-6 mg·kg-1). Opioid receptor specificity was investigated using naloxone (6 mg·kg-1). We investigated the possible role of stress in increasing cardiorespiratory toxicity using the corticotropin-releasing factor 1 (CRF1) antagonist antalarmin (10 mg·kg-1). KEY RESULTS: Agonists displayed the following rank of potency at µ receptors: fentanyl > 4F-BUF > BUF. Fentanyl and BUF behaved as partial agonists for the ß-arrestin 2 pathway, whereas 4F-BUF did not promote ß-arrestin 2 recruitment. In vivo, we revealed sex differences in motor and cardiorespiratory impairments but not antinociception induced by BUF and 4F-BUF. Antalarmin alone was effective in blocking respiratory impairment induced by BUF in both sexes but not 4F-BUF. The combination of naloxone and antalarmin significantly enhanced naloxone reversal of the cardiorespiratory impairments induced by BUF and 4F-BUF in mice. CONCLUSION AND IMPLICATIONS: In this study, we have uncovered a novel mechanism by which synthetic opioids induce respiratory depression, shedding new light on the role of CRF1 receptors in cardiorespiratory impairments by µ agonists.

Genetic Associations of Persistent Opioid Use After Surgery Point to OPRM1 but Not Other Opioid-Related Loci as the Main Driver of Opioid Use Disorder.

Persistent opioid use after surgery is a common morbidity outcome associated with subsequent opioid use disorder, overdose, and death. While phenotypic associations have been described, genetic associations remain unidentified. Here, we conducted the largest genetic study of persistent opioid use after surgery, comprising ~40,000 non-Hispanic, European-ancestry Michigan Genomics Initiative participants (3198 cases and 36,321 surgically exposed controls). Our study primarily focused on the reproducibility and reliability of 72 genetic studies of opioid use disorder phenotypes. Nominal associations (p < 0.05) occurred at 12 of 80 unique (r2 < 0.8) signals from these studies. Six occurred in OPRM1 (most significant: rs79704991-T, OR = 1.17, p = 8.7 × 10-5), with two surviving multiple testing correction. Other associations were rs640561-LRRIQ3 (p = 0.015), rs4680-COMT (p = 0.016), rs9478495 (p = 0.017, intergenic), rs10886472-GRK5 (p = 0.028), rs9291211-SLC30A9/BEND4 (p = 0.043), and rs112068658-KCNN1 (p = 0.048). Two highly referenced genes, OPRD1 and DRD2/ANKK1, had no signals in MGI. Associations at previously identified OPRM1 variants suggest common biology between persistent opioid use and opioid use disorder, further demonstrating connections between opioid dependence and addiction phenotypes. Lack of significant associations at other variants challenges previous studies' reliability.

Supporting medication-assisted recovery in recovery residences: staff support, managing built environment threats, and building a supportive network.

Background: While medications for opioid use disorder (MOUD) are effective in reducing overdoses, widespread adoption and implementation of MOUD remains inadequate. Innovative approaches to promote MOUD use and to support people in their medication-assisted recovery (MAR) are needed. Recovery residences that serve people taking MOUD are steadily growing in number, yet little is known about how MOUD and the MAR pathway is promoted within the recovery residence setting.Objectives: The purpose of this qualitative analysis was to describe how recovery residences facilitate MOUD initiation and support residents' MAR pathway.Methods: We conducted interviews with 93 residents (59.1% male; 38.7% female) living in recovery residences located in five Texas cities that served people taking medication for opioid use disorder.Results: We found that recovery residence staff addressed linkage to care gaps in their communities by connecting people who might benefit from MOUD to appropriate providers. Recovery residence staff also strengthened participants' community of MAR-supportive peers by hosting or connecting residents to Medication-Assisted Recovery Anonymous meetings. Additionally, recovery residences helped some residents overcome common logistical barriers (e.g. transportation issues, housing instability, distance to providers) that hinder MOUD access.Conclusion: Recovery residences that serve people taking MOUD are a well-positioned recovery support service to promote MOUD initiation and the MAR pathway.

Stimulation of kappa opioid receptors in the nucleus accumbens promotes feeding behavior in mice: Acute restoration of feeding during anorexia induced by 5-fluorouracil.

Though µ and δ opioid receptors are reported to regulate energy homeostasis, any role for κ opioid receptors in these processes remains unclear. The present study investigated the role of κ opioid receptors in regulation of feeding behavior and plasma glucose levels using nalfurafine, a κ opioid receptor agonist used clinically. Systemic injection of nalfurafine increased food intake under non-fasted conditions, but not after food deprivation, and this effect was inhibited by the κ opioid receptor antagonist norbinaltorphimine. In contrast, nalfurafine did not affect plasma glucose levels. I.c.v. injection of nalfurafine increased food intake, whereas systemic injection of nalfurafine methiodide, which does not penetrate the blood brain barrier, was without effect. In addition, nalfurafine tended to increase preproorexin mRNA in the hypothalamus. However, neither the orexin OX1 receptor antagonist YNT-1310 nor the non-selective orexin receptor antagonist suvorexant inhibited the increase in food intake induced by nalfurafine. While nalfurafine injected into the lateral hypothalamus did not affect food intake, nalfurafine injected into the nucleus accumbens increased food intake, which was inhibited by norbinaltorphimine. Finally, we examined the effect of nalfurafine on anorexia induced by the anti-cancer agent 5-fluorouracil. Reduced food intake at 2 days following 5-fluorouracil administration was alleviated across the first 3 h following daily injection of nalfurafine, though daily food intake was not influenced. These results indicate that nalfurafine promotes feeding behavior through stimulation of κ opioid receptors in the nucleus accumbens and may be a candidate for reducing anorexia due to anti-cancer agents.