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ImportanceThe incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA.ObjectiveTo evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA.Design, setting, and participantsRetrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024.ExposureEMS administration of naloxone.Main outcomes and measuresThe primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related.ResultsAmong 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77).Conclusions and relevanceIn this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.

Background: Gambling disorder (GD) is a psychiatric disorder classified in the DSM-5 as a non-substance-related and addictive disorder with extensive health and socioeconomic impacts. Its chronic and high-relapsing nature makes it essential to find treatment strategies that improve functioning and reduce impairment associated with it. The purpose of this narrative review is to evaluate and summarize the available evidence on the effectiveness and safety of pharmacotherapy in GD. Methods: An electronic literature search of Medline, Embase, and Cochrane Central was conducted to identify systematic reviews, meta-analyses, and reviews on pharmacological interventions in patients with gambling disorder. A similar search of these databases and of Prospero, Clinicaltrials.gov, and Epistemonikos was conducted to identify clinical trials that were published since 2019. Results: The initial search identified 1925 articles. After screening and duplicate removal, 18 articles were included in the review (11 studies were systematic reviews and meta-analyses, 6 were reviews, and 1 was an open-label trial). Eight pharmacological agents (naltrexone, nalmefene, paroxetine, fluvoxamine, citalopram, escitalopram, lithium, and topiramate) that were studied in randomized controlled trials and open-label trials showed small to moderate effect sizes in reducing GD symptoms in some studies during post-hoc analyses. Conclusion: The overall sum of evidence in the literature on the use of pharmacotherapy in GD is conflicting and inconclusive. Some studies have shown that pharmacotherapy's role in GD is promising, especially when the choice of the agent is guided by comorbid psychiatric disorders. However, significant limitations exist in the study designs, which need to be addressed in future research on the topic. Conducting future and more rigorous trials that address the limitations in the existing literature is necessary to establish more accurate efficacy data on the use of pharmacotherapy in this population. [ABSTRACT FROM AUTHOR]

Background: The use of opioids occasionally causes tinnitus. However, there is a paucity of data regarding the use of peripherally acting μ-opioid receptor antagonists for opioid-associated tinnitus in patients with cancer. Actual case: A 74-year-old male with pancreatic cancer complained of abdominal pain. Two days after initiating oxycodone therapy, the patient experienced tinnitus during body movements. Although peripheral tinnitus disappeared after discontinuing oxycodone, it reappeared with hydromorphone or tapentadol administration. Possible courses of action: Drug cessation is a preferred intervention for drug-induced tinnitus; however, the cessation of opioids may not be feasible in patients with cancer who are already taking opioids. Formulation of a plan: Based on the presumed mechanism of peripheral tinnitus, the use of peripherally acting μ-opioid receptor antagonists was planned, and 200 μg/day of naldemedine was prescribed for tinnitus relief. Outcome: Tinnitus disappeared immediately after initiating naldemedine, and the pain was well-controlled. The effect was preserved after increasing or switching opioids. Lessons: The use of peripherally acting μ-opioid receptor antagonists may be an option to treat opioid-associated tinnitus without compromising the analgesic effects. View: Further clinical data regarding the secondary effect of peripherally acting μ-opioid receptor antagonists on opioid-associated complications other than constipation are required. [ABSTRACT FROM AUTHOR]

Background and aims: Extended release buprenorphine injection (INJ‐BUP) has been available in the United States since 2018. INJ‐BUP has the potential to positively impact opioid use disorder (OUD) treatment outcomes by providing additional treatment options. As one of the largest payers of OUD treatment in the US, Medicaid coverage is important for access and uptake of INJ‐BUP. Uptake of INJ‐BUP among Medicaid beneficiaries has not been described since 2019 and variation in uptake by state has not previously been explored. We aimed to measure prescribing of INJ‐BUP for Medicaid beneficiaries since 2018, nationwide and by state. Methods: We analyzed State Drug Utilization Data from 2017 to 2022 and calculated the number of prescription fills for INJ‐BUP and oral buprenorphine paid by Medicaid. To compare across states, we calculated the number of prescription fills per 100 Medicaid beneficiaries treated for OUD using data from Transformed Medicaid Statistical Information System Substance Use Disorder (T‐MSIS SUD) Data Books. Data sources are publicly available. Results: The number of prescription fills for INJ‐BUP paid by Medicaid increased from 4322 (0.1% of all buprenorphine prescription fills) in 2018 to 186 861 (2.0%) in 2022. Each year the increase in fills exceeded the prior year change, indicating accelerating uptake. There was notable variability across states. Conclusions: The number of extended release buprenorphine injection prescriptions among US Medicaid beneficiaries treated for opioid use disorder increased from over 4000 prescriptions in 2018 to over 185 000 in 2022 but uptake is much less than observed in other countries over shorter time periods. [ABSTRACT FROM AUTHOR]

Background: While laypersons can play a crucial role in administering naloxone in opioid overdoses, they must be recruited and trained to effectively manage overdose events as good Samaritans. This study aimed to examine the effectiveness of a technology-based intervention that recruited and trained laypersons to administer naloxone. Methods: Opioid Rapid Response System (ORRS) was an online recruitment and training intervention which capitalized on social cognitive theory and a digital media engagement model to mobilize laypersons to administer intranasal naloxone. ORRS was developed based on a randomized waitlisted controlled trial (N = 220). This secondary analysis is a within-group, extended-baseline assessment of the waitlisted group (n = 106), considering that they served as their own control prior to receiving the training. ORRS was conducted in five counties of Indiana with adults who did not self-identify as a certified first responder. Five indices were generated from 23 variables: knowledge of overdose signs, knowledge of overdose management, self-efficacy in responding, concerns about responding, and intent to respond. Paired t-test compared changes between 3 timepoints. Results: Three indices had significantly greater increases associated with training compared to extended baseline: recognizing opioid overdose signs (difference = 0.08; 95%CI = 0.02, 0.15; t = 2.48; p = 0.01); knowledge of overdose management (difference = 0.27; 95%CI = 0.18, 0.35; t = 5.99; p < 0.01); and self-efficacy in overdose management (difference = 0.68; 95%CI = 0.45, 0.91; t = 5.78; p < 0.01). Concerns related to overdose management significantly decreased as expected (difference = −1.53; 95%CI = −1.86, −1.21; t = −9.27; p < 0.01). Conclusions: ORRS provided strong support for self-efficacy, concerns, and knowledge related to overdose management, and the digital modality accelerates largescale dissemination. [ABSTRACT FROM AUTHOR]

Background and aims: Drug-related deaths in Scotland more than doubled between 2011 and 2020. To inform policymakers and understand drivers of this increase, we estimated the number of people with opioid dependence aged 15-64 from 2014/15 to 2019/20. Design: We fitted a Bayesian multi-parameter estimation of prevalence (MPEP) model, using adverse event rates to estimate prevalence of opioid dependence jointly from Opioid Agonist Therapy (OAT), opioid-related mortality and hospital admissions data. Estimates are stratified by age group, sex and year. Setting: Scotland, 2014/15 to 2019/20. Participants: People with opioid dependence and potential to benefit from OAT, whether ever treated or not. Using data from the Scottish Public Health Drug Linkage Programme, we identified a baseline cohort of individuals who had received OAT within the last 5 years, and all opioid-related deaths and hospital admissions (whether among or outside of this cohort). Measurements: Rates of each adverse event type and (unobserved) prevalence were jointly modelled. Findings: The estimated number and prevalence of people with opioid dependence in Scotland in 2019/20 was 47 100 (95% Credible Interval [CrI] 45 700 to 48 600) and 1.32% (95% CrI 1.28% to 1.37%). Of these, 61% received OAT during 2019/20. Prevalence in Greater Glasgow and Clyde was estimated as 1.77% (95% CrI 1.69% to 1.85%). There was weak evidence that overall prevalence fell slightly from 2014/15 (change -0.07%, 95% CrI -0.14% to 0.00%). The population of people with opioid dependence is ageing, with the estimated number of people aged 15-34 reducing by 5100 (95% CrI 3800 to 6400) and number aged 50-64 increasing by 2800 (95% CrI 2100 to 3500) between 2014/15 and 2019/20. Conclusions: The prevalence of opioid dependence in Scotland remained high but was relatively stable, with only weak evidence of a small reduction, between 2014/15 and 2019/20. Increased numbers of opioid-related deaths can be attributed to increased risk among people with opioid dependence, rather than increasing prevalence. [ABSTRACT FROM AUTHOR]

Background and Aims: Opioid use disorder often co‐occurs with chronic pain but assessment and treatment of these co‐occurring disorders is complex. This review aims to identify current treatments and delivery models for co‐occurring chronic pain and opioid use disorder (OUD) documented in the scientific literature. Design: Scoping review. Methods: The review was conducted in six databases in June 2022 (no time limit): CINAHL, PsycINFO, Web of Science, Cochrane, PubMed and Embase. The PRISMA‐ScR checklist was used to guide reporting. Results: Forty‐seven publications addressing the issue of co‐occurring chronic pain and OUD management were included. Randomized controlled trials provide evidence for the effectiveness of opioid agonist treatments (OAT) such as methadone or buprenorphine/naloxone, as well as for combining OAT with Mindfulness‐Oriented Recovery Enhancement or cognitive behavioural therapy. A number of other pharmacological treatments (opioid and nonopioid), nonpharmacological treatments (e.g. physiotherapy) and service delivery models (e.g. simultaneous treatment of comorbidities, interdisciplinary and interprofessional collaboration) are also underlined. In most cases, authors recommend a combination of strategies to meet patient needs. Conclusions: The scoping review reveals gaps in evidence‐based knowledge to effectively care for co‐occurring chronic pain and OUD, but several experts recommend the uptake of known 'best' practices such as integrated treatment of the multiple biopsychosocial dimensions of the co‐occurring disorders as well as collaborative interdisciplinary work. Clinical Relevance: Improving services is dependent on alleviating barriers such as working in silos, the costs associated with nonpharmacological treatments, and the double stigma associated with pain in people with a substance use disorder. [ABSTRACT FROM AUTHOR]

Background: Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. Method: Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. Results: The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5 mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS. Conclusion: Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS. [ABSTRACT FROM AUTHOR]

Introduction: To expand access to naloxone, the state of Illinois implemented a standing order allowing registered pharmacies to dispense the drug without an individual prescription. To participate under the standing order, pharmacies were required to opt in through a formal registration process. In our study we aimed to evaluate the availability and price of naloxone at registered pharmacies. Methods: This was a prospective, de-identified, cross-sectional telephone survey. Trained interviewers posed as potential customers and used a standardized script to determine the availability of naloxone between February-December, 2019. The primary outcome was defined as a pharmacy indicating it carried naloxone, currently had naloxone in stock, and was able to dispense it without an individual prescription. Results: Of 948 registered pharmacies, 886 (93.5%) were successfully contacted. Of those, 792 (83.4%) carried naloxone, 659 (74.4%) had naloxone in stock, and 472 (53.3%) allowed purchase without a prescription. Naloxone nasal spray (86.4%) was the formulation most commonly stocked. Chain pharmacies were more likely to carry naloxone (adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI] 1.97-5.01, P < 0.01) and have naloxone in stock (aOR 2.72, 95% CI 1.76-4.20, P < 0.01), but no more likely to dispense it without a prescription. Pharmacies in higher population areas (aOR 0.99, 95% CI 0.99-0.99, P < 0.05) and rural areas adjacent to metropolitan areas (aOR 0.5, 95% CI 025-0.98, P < 0.05) were less likely to have naloxone available without a prescription. Associations of naloxone availability based on other urbanicity designations, overdose count, and overdose rate were not significant. Conclusion: Among pharmacies in Illinois that formally registered to dispense naloxone without a prescription, the availability of naloxone remains limited. Additional interventions may be needed to maximize the potential impact of a statewide standing order. [ABSTRACT FROM AUTHOR]

An open‐label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil‐induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT 04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight‐fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time‐dependent reversal of remifentanil‐induced reductions in MV measured 2.5–20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P <.0009); the point estimate favors nalmefene, demonstrating non‐inferiority and superiority. In this model of opioid‐induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose. [ABSTRACT FROM AUTHOR]

Aim. The aim of the study was to review the existing research, conducted on animal and human models, regarding the possibility of using low doses of naltrexone (LDN) in treatment of non-suicidal self-injury (NSSI). Method. The available Polish- and English-language literature on NSSI was reviewed. Relevant studies were identified through an electronic search of PubMed/MEDLINE and Google Scholar databases using the following keywords: non-suicidal self-injury, NSSI, naltrexone, LDN, self-injury, self-harm, and time descriptors 1982-2022. The review was based on information reported in original papers, review articles and case reports. The quality of the article was assessed using the six-point Scale for the Assessment of Narrative Review Articles (SANRA). Results. Studies conducted on animal models show that use of LDN can prevent habitual self-injury. As far as the possibility of clinical use of LDN in treatment of NSSI is concerned, results of a relatively small number of studies conducted so far confirm the efficacy of using naltrexone 25-50 mg/day to decrease or eliminate self-injurious behaviors in NSSI patients. Conclusions. The use of LDN in treatment of NSSI seems to be a promising clinical option, whose efficacy, however, needs to be corroborated in a larger number of randomized placebo-controlled clinical trials. [ABSTRACT FROM AUTHOR]

Background and aims: Identifying effective opioid treatment options during pregnancy is a high priority due to the growing prevalence of opioid use disorder across North America. We assessed the temporal impact of three population‐level interventions on the use of opioid agonist treatment (OAT) during pregnancy in Ontario, Canada. Design: This was a population‐based time‐series analysis to identify trends in the monthly prevalence of pregnant people dispensed methadone and buprenorphine. The impact of adding buprenorphine/naloxone to the public drug formulary, the release of pregnancy‐specific guidance and the start of the COVID‐19 pandemic were assessed. Setting and participants: The study was conducted in Ontario, Canada between 1 July 2013 and 31 March 2022, comprising people who delivered a live or stillbirth in any Ontario hospital during the study period. Measurements We identified any prescription for methadone or buprenorphine dispensed between the estimated conception date and delivery date and calculated the monthly prevalence of OAT‐exposed pregnancies among all pregnant people in Ontario. Findings Overall, rates of OAT during pregnancy have declined since mid‐2018. Methadone‐exposed pregnancies decreased from 0.46% of all pregnancies in Ontario in 2015 to a low of 0.16% in 2022. In the primary analysis, none of the interventions had a statistically significant impact on overall OAT rates; however, in the stratified analyses, there was a small increase in buprenorphine after the formulary change [0.006%, 95% confidence interval (CI) = 0.0032−0.0081, P < 0.0001] and a decrease in buprenorphine after the release of the 2017 guidelines (−0.005%, 95% CI = −0.0080 to −0.0020, P = 0.001) and the start of the COVID‐19 pandemic (−0.003%, 95% CI = −0.0054 to −0.0006, P = 0.015). Conclusion: Despite changes in guidance and funding, opioid agonist treatment during pregnancy has been declining in Ontario, Canada since 2018. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Constipation is a distressing symptom that has a high prevalence in patients receiving hospice and palliative care services, particularly in cases of opioid use. A thorough assessment, root cause analysis, monitoring, and prophylactic approach are essential for symptom management and quality of life. This rapid review assessed studies published between 2018 and 2023 to identify strategies implemented by health care professionals to prevent and/or mitigate this distressing symptom. We identified 12 articles that addressed constipation in palliative and end-of-life settings and reported on the need for multifactorial management approaches with a focus on patient-centered care that includes the caregiver(s). Bedside nurses play a key role in assessing, identifying, and managing constipation. Proper documentation and communication with the interdisciplinary team help direct earlier intervention and ongoing awareness of constipation issues. Additional research is needed on specific tools and enhanced guidelines to ensure constipation is frequently addressed and preemptively managed. [ABSTRACT FROM AUTHOR]

BACKGROUND: More than half a million Americans died of an opioid-related overdose between 1999 and 2020, the majority occurring between 2015 and 2020. The opioid overdose mortality epidemic disproportionately impacts Black, Indigenous, and people of color (BIPOC): since 2015, overdose mortality rates have increased substantially more among Black (114%) and Latinx (97%) populations compared with White populations (32%). This is in part due to disparities in access to naloxone, an opioid antagonist that can effectively reverse opioid overdose to prevent death. Our recent pilot work determined that many barriers to naloxone access can be identified and addressed by syringe service programs (SSPs) using the Systems Analysis and Improvement Approach to Naloxone distribution (SAIA-Naloxone). This randomized controlled trial will test SAIA-Naloxones ability to improve naloxone distribution in general and among BIPOC specifically. METHODS: We will conduct a trial with 32 SSPs across California, randomly assigning 16 to the SAIA-Naloxone arm and 16 to receive implementation as usual. SAIA-Naloxone is a multifaceted, multilevel implementation strategy through which trained facilitators work closely with SSPs to (1) assess organization-level barriers, (2) prioritize barriers for improvement, and (3) test solutions through iterative change cycles until achieving and sustaining improvements. SSPs receiving SAIA-Naloxone will work with a trained facilitator for a period of 12 months. We will test SAIA-Naloxones ability to improve SSPs naloxone distribution using an interrupted time series approach. Data collection will take place during a 3-month lead-in period, the 12-month active period, and for an additional 6 months afterward to determine whether impacts are sustained. We will use a structured approach to specify SAIA-Naloxone to ensure strategy activities are clearly defined and to assess SAIA-Naloxone fidelity to aid in interpreting study results. We will also assess the costs associated with SAIA-Naloxone and its cost-effectiveness. DISCUSSION: This trial takes a novel approach to improving equitable distribution of naloxone amid the ongoing epidemic and associated racial disparities. If successful, SAIA-Naloxone represents an important organizational-level solution to the multifaceted and multilevel barriers to equitable naloxone distribution.

IntroductionMethamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial.MethodsThe multi-site ADAPT-2 study used a randomized, double blind, sequential parallel comparison design to evaluate treatment with extended-release injectable NTX (380 mg every 3 weeks) combined with once-daily oral extended-release BUP (450 mg/day) vs matching injectable and oral placebo in outpatients with moderate or severe MA use disorder. The study assessed smoking outcomes, based on self-reported timeline followback (TLFB) data, twice/week for 13 weeks.ResultsOf the 403 participants in the ADAPT-2 trial, 290 reported being current cigarette smokers (71.9 %). The study found significant differences (p's

Opioids are an integral component of pain management for nonhuman primates. These potent analgesics also adverse gastrointestinal (GI) effects that include constipation, bloating, and delayed gastric emptying. Methylnaltrexone bromide (MNTX) is a selective, peripherally acting μ- and κ-opioid receptor antagonist that can be used to mitigate the GI effects associated with opioid administration. Unlike naltrexone, a similar drug in this class, MNTX possesses an N-methyl-quaternary amine group that prevents it from crossing the blood brain barrier. This blockage allows inhibition of peripheral GI opioid receptors without affecting opioid-mediated analgesia in the central nervous system. We conducted a pharmacokinetic analysis of MNTX in serum and CSF of 6 healthy juvenile male rhesus macaques after subcutaneous administration of a 0.15-mg/kg dose. We hypothesized that the macaques would demonstrate a Tmax of 0.5 h, similar to that of humans, and that no MNTX would be detected in the CSF. This treatment resulted in a peak serum concentration of 114 ± 44 ng/mL at 0.25 ± 0.00 h; peak CSF at concentrations were 0.34 ± 0.07 ng/mL at the Tmax. These data show that subcutaneous administration of MNTX to rhesus macaques may block peripheral adverse effects of opioids without interfering with their central analgesic effects.

BACKGROUND: Opioid overdose fatalities are preventable with timely administration of naloxone, an opioid antagonist, during an opioid overdose event. Syringe service programs have pioneered naloxone distribution for potential bystanders of opioid overdose. The objective of this study was to pilot test a multi-component implementation strategy-the systems analysis and improvement approach for naloxone (SAIA-Naloxone)-with the goal of improving naloxone distribution by syringe service programs. METHODS: Two syringe service programs participated in a 6-month pilot of SAIA-Naloxone, which included (1) analyzing program data to identify gaps in the naloxone delivery cascade, (2) flow mapping to identify causes of attrition and brainstorm programmatic changes for improvement, and (3) conducting continuous quality improvement to test and assess whether modifications improve the cascade. We conducted an interrupted time series analysis using 52 weeks of data before and 26 weeks of data after initiating SAIA-Naloxone. Poisson regression was used to evaluate the association between SAIA-Naloxone and the weekly number of participants receiving naloxone and number of naloxone doses distributed. RESULTS: Over the course of the study, 11,107 doses of naloxone were distributed to 6,071 participants. Through SAIA-Naloxone, syringe service programs prioritized testing programmatic modifications to improve data collection procedures, proactively screen and identify naloxone-naïve participants, streamline naloxone refill systems, and allow for secondary naloxone distribution. SAIA-Naloxone was associated with statistically significant increases in the average number of people receiving naloxone per week (37% more SPP participants; 95% CI, 12% to 67%) and average number of naloxone doses distributed per week (105% more naloxone doses; 95% CI, 79% to 136%) beyond the underlying pre-SAIA-Naloxone levels. These initial increases were extended by ongoing positive changes over time (1.6% more SSP participants received naloxone and 0.3% more naloxone doses were distributed in each subsequent week compared to the weekly trend in the pre-SAIA Naloxone period). CONCLUSIONS: SAIA-Naloxone has strong potential for improving naloxone distribution from syringe service programs. These findings are encouraging in the face of the worsening opioid overdose crisis in the United States and support testing SAIA-Naloxone in a large-scale randomized trial within syringe service programs.

The opioid G-protein coupled receptors (GPCRs) strongly modulate many of the central nervous system structures that contribute to neurological and psychiatric disorders including pain, major depressive disorder, and substance use disorders. To better treat these and related diseases, it is essential to understand the signaling of their endogenous ligands. In this review, we focus on what is known and unknown about the regulation of the over two dozen endogenous peptides with high affinity for one or more of the opioid receptors. We briefly describe which peptides are produced, with a particular focus on the recently proposed possible synthesis pathways for the endomorphins. Next, we describe examples of endogenous opioid peptide expression organization in several neural circuits and how they appear to be released from specific neural compartments that vary across brain regions. We discuss current knowledge regarding the strength of neural activity required to drive endogenous opioid peptide release, clues about how far peptides diffuse from release sites, and their extracellular lifetime after release. Finally, as a translational example, we discuss the mechanisms of action of naltrexone (NTX), which is used clinically to treat alcohol use disorder. NTX is a synthetic morphine analog that non-specifically antagonizes the action of most endogenous opioid peptides developed in the 1960s and FDA approved in the 1980s. We review recent studies clarifying the precise endogenous activity that NTX prevents. Together, the works described here highlight the challenges and opportunities the complex opioid system presents as a therapeutic target.

BackgroundCalifornia has sought to expand medication access and improve public health by authorizing pharmacists in California to prescribe certain medications since 2014. Medications with pharmacist-initiated prescribing, or furnishing, include naloxone, hormonal contraception, postexposure prophylaxis/preexposure prophylaxis, and nicotine replacement therapy. In light of the United States' opioid epidemic, naloxone, an opioid antagonist, this study considered furnishing rates in urban areas of California. Research from 2020 found 42.5% of pharmacies furnished naloxone. However, there has been limited study of furnishing outside of urban areas.ObjectiveThis study assessed pharmacist furnishing rates of naloxone in California's Central Valley and identified barriers and facilitators to implementation.MethodsFrom April to May 2022, the researchers first conducted a cross-sectional, observational study of community and mail-order pharmacies in California's largely rural Central Valley, then collected interview data from a subset of pharmacists in stores that indicated they furnished naloxone.ResultsForty-three percent of Central Valley pharmacies reported that they furnished naloxone. Interview respondents reported that barriers to furnishing included time restrictions, cost to patients, stigma, and language barriers.ConclusionsFurnishing rates in the Central Valley were slightly higher (43.4%) than those reported in previous research focusing on urban areas of California (42.5%). Identified barriers to furnishing were consistent with those identified in previous research. These findings suggest that further policy interventions may be needed to reduce out-of-pocket costs, establish stronger pharmacist-provider relationships, and provide education combatting stigma against opioid users to increase naloxone furnishing.

BackgroundBuprenorphine is an effective treatment for opioid use disorders. A previous randomized trial comparing emergency department (ED)-initiated buprenorphine to standard care showed dramatic improvement in follow-up. This is encouraging, but must be replicated to understand the generalizability of buprenorphine treatment.ObjectivesEvaluate the efficacy of an ED-initiated buprenorphine protocol similar to a previous randomized trial in a different population.MethodsThis ED-based descriptive study described the results of a project implementing an opioid use disorder treatment protocol that included buprenorphine. Patients with opioid use disorder were offered treatment with buprenorphine, a buprenorphine prescription whenever possible, and a follow-up visit to a clinic providing addiction treatment. The primary outcome was engagement in formal addiction treatment 30 days after the index visit.ResultsOf the 210 patients who accepted referral for outpatient medication-assisted treatment, 95 (45.2%) achieved the primary outcome. Two-thirds of these patients received a buprenorphine prescription at discharge; 40% were homeless. A regression analysis revealed one statistically significant predictor of the primary outcome: patients who were housed were 2.49 times more likely to engage in opioid use disorder treatment than patients who were homeless (p = 0.02).ConclusionsIn this descriptive study of an ED-initiated buprenorphine protocol, follow-up was less than that reported in a previous randomized controlled trial. Two important differences between our study and the randomized trial are the high rate of homelessness and the fact that not every patient received a prescription for buprenorphine. The efficacy of ED-initiated treatment may depend on certain population characteristics.

Most people with co-occurring opioid use disorder (OUD) and mental illness do not receive effective medications for treating OUD. To investigate perspectives of adults in a publicly-funded mental health system regarding medications for OUD (MOUD), we conducted semi-structured telephone interviews with 13 adults with OUD (current or previous diagnosis) receiving mental health treatment. Themes that emerged included: perceiving or using MOUDs as a substitute for opioids or a temporary solution to prevent withdrawal symptoms; negative perceptions about methadone/methadone clinics; and viewing MOUD use as "cheating". Readiness to quit was important for patients to consider MOUDs. All participants were receptive to discussing MOUDs with their mental health providers and welcomed the convenience of receiving care for their mental health and OUD at the same location. In conclusion, clients at publicly-funded mental health clinics support MOUD treatment, signaling a need to expand access and build awareness of MOUDs in these settings.

BackgroundDespite the widespread availability of naloxone, US opioid overdose rates continue to rise. The "Cascade of Care" (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors.MethodsPatients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors.ResultsParticipants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02-8.52), college education (aOR = 8.11, 95% CI 1.76-37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00-2.11).ConclusionWe found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.

Introduction: Bystander provision of naloxone is a key modality to reduce opioid overdose-related death. Naloxone training courses are available, but no standardized program exists. As part of a bystander empowerment course, we created and evaluated a brief naloxone training module. Methods: This was a retrospective evaluation of a naloxone training course, which was paired with Stop the Bleed training for hemorrhage control and was offered to administrative staff in an office building. Participants worked in an organization related to healthcare, but none were clinicians. The curriculum included the following topics: 1) background about the opioid epidemic; 2) how to recognize the signs of an opioid overdose; 3) actions not to take when encountering an overdose victim; 4) the correct steps to take when encountering an overdose victim; 5) an overview of naloxone products; and 6) Good Samaritan protection laws. The 20-minute didactic section was followed by a hands-on session with nasal naloxone kits and a simulation mannequin. The course was evaluated with the Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales for take-home naloxone training evaluation. We used the paired Wilcoxon signed-rank test to compare scores pre- and post-course. Results: Twenty-eight participants completed the course. The OOKS, measuring objective knowledge about opioid overdose and naloxone, had improved scores from a median of 73.2% (interquartile range [IQR] 68.3%-79.9%) to 91.5% (IQR 85.4%-95.1%), P < 0.001. The three domains on the OOAS score also showed statistically significant results. Competency to manage an overdose improved on a fivepoint scale from a median of 2.5 (IQR 2.4-2.9) to a median of 3.7 (IQR 3.5-4.1), P < 0.001. Concerns about managing an overdose decreased (improved) from a median of 2.3 (IQR 1.9-2.6) to median 1.8 (IQR 1.5-2.1), P < 0.001. Readiness to intervene in an opioid overdose improved from a median of 4 (IQR 3.8-4.2) to a median of 4.2 (IQR 4-4.2), P < 0.001. Conclusion: A brief course designed to teach bystanders about opioid overdose and naloxone was feasible and effective. We encourage hospitals and other organizations to use and promulgate this model. Furthermore, we suggest the convening of a national consortium to achieve consensus on program content and delivery. [ABSTRACT FROM AUTHOR]

Addressing inadequacies in the implementation of existing evidence-based approaches into practice, such as injectable opioid agonist treatment (iOAT), is imperative for the management of opioid use disorder. With the expansion of iOAT, stakeholder perspectives are needed to inform program optimization. This study aimed to understand stakeholder and provider perspectives on iOAT care and how it can be improved to better meet service users' needs. Semi-structured interviews (n = 11), email correspondence (n = 2), a focus group (n = 4), and one regional meeting were conducted with iOAT stakeholders to receive feedback on how iOAT can better meet service users' needs. Qualitative analysis employed a thematic and interpretive description approach to identify key themes, presented as a thematic summary. Stakeholder narratives highlight the importance they attribute to client autonomy, individualized care, tensions between providers and the system (policies, governing structures, etc., that establish, facilitate and determine how iOAT is delivered in Canada) as well as power dynamics between providers and service users. IOAT providers and stakeholders surveyed in this study are committed to seeing the needs of service users met but often feel constrained by system-level regulations that influence power dynamics between providers and service users. Findings underline pragmatic suggestions to advance person-centered care as a way to make iOAT accessible and individualized. [ABSTRACT FROM AUTHOR]

ObjectivesIn the setting of a 50% increase in opioid overdose deaths, the coronavirus disease 2019 crisis opened housing opportunities in the form of Shelter in Place (SIP) hotels to homeless San Francisco residents. Many who entered SIP hotels had opioid use disorder. In fall 2020, Community Behavioral Health Services Pharmacy partnered with SIP hotel medical staff to launch a pilot project, where on-site SIP medical providers prescribed buprenor-phine (BUP) and clinical pharmacists hand-delivered BUP to SIP residents to increase BUP initiation and engagement.MethodsA retrospective chart review of 3 patients living in SIP hotels starting BUP to demonstrate the feasibility of a SIP hotel BUP delivery program.ResultsIn all 3 cases, patients were able to start and continue BUP with on-site medical staff visits and delivery of medications by pharmacists. Each case highlights different barriers that were overcome by this system.ConclusionsOur findings suggest that this system of onsite medical care with pharmacist delivery is possible and has the potential to allow for greater outreach and increased ease of obtaining medications for patients.

Low dopamine D2 receptor (D2R) availability in the striatum can predispose for cocaine abuse; though how low striatal D2Rs facilitate cocaine reward is unclear. Overexpression of D2Rs in striatal neurons or activation of D2Rs by acute cocaine suppresses striatal Penk mRNA. Conversely, low D2Rs in D2-striatal neurons increases striatal Penk mRNA and enkephalin peptide tone, an endogenous mu-opioid agonist. In brain slices, met-enkephalin and inhibition of enkephalin catabolism suppresses intra-striatal GABA transmission. Pairing cocaine with intra-accumbens met-enkephalin during place conditioning facilitates acquisition of preference, while mu-opioid receptor antagonist blocks preference in wild-type mice. We propose that heightened striatal enkephalin potentiates cocaine reward by suppressing intra-striatal GABA to enhance striatal output. Surprisingly, a mu-opioid receptor antagonist does not block cocaine preference in mice with low striatal D2Rs, implicating other opioid receptors. The bidirectional regulation of enkephalin by D2R activity and cocaine offers insights into mechanisms underlying the vulnerability for cocaine abuse.

BackgroundFentanyl has replaced most other non-prescribed opioids in much of North America. There is controversy over whether a hypothetical reduced efficacy of naloxone in reversing fentanyl is a major contributor to the coincident rising overdose mortality.MethodsWe modified an existing Markov decision analytic model of heroin overdose and naloxone distribution to account for known risks of fentanyl by adjusting overdose risk, the likelihood of death in the event of overdose, and the proportion of cases in which available naloxone was administered in time to prevent death. We assumed near-universal survival when naloxone was administered promptly for heroin or fentanyl overdose, but allowed that to decline in sensitivity analyses for fentanyl. We varied the proportion of use that was fentanyl and adjusted the modified parameters accordingly to estimate mortality as the dominant opioid shifted.ResultsAbsent naloxone, the annual overdose death rate was 1.0% and 4.1% for heroin and fentanyl, respectively. With naloxone reaching 80% of those at risk, the overdose death rate was 0.7% and 3.6% for heroin and fentanyl, respectively, representing reductions of 26.4% and 12.0%. Monte Carlo simulations resulted in overdose mortality with fentanyl of 3.3-5.2% without naloxone and 2.6-4.9% with naloxone, with 95% certainty. Positing reduced efficacy for naloxone in reversing fentanyl resulted in 3.6% of fentanyl overdose deaths being prevented by naloxone.ConclusionsHeightened risk for overdose and subsequent death, alongside the time-sensitive need for naloxone administration, fully account for increased mortality when fentanyl replaces heroin, assuming optimal pharmacologic efficacy of naloxone.

Background: Women face unique barriers when seeking treatment for substance use disorders, often related to pregnancy and parenting. Objectives: This study adds to the extant literature by elucidating the pregnancy- and parenting-related barriers women face when initiating or continuing medication for opioid use disorder, specifically. Design: This study is based on qualitative semi-structured interviews. Methods: Three subgroups participated in semi-structured interviews regarding their experiences (N = 42): women with current or past opioid use disorders who have used or were presently using medication for opioid use disorder, professionals working in substance use disorder treatment programs, and criminal justice professionals. Results: Three parenting-related subthemes were identified: (1) insufficient access to childcare to navigate appointments and meetings, (2) fear of losing custody of, or access to, one's children, and (3) prioritizing one's children's needs before one's own. Three subthemes were identified with regard to pregnancy as a barrier: (1) hesitancy among physicians to prescribe medication for opioid use disorder for pregnant patients, (2) limited access to resources in rural areas, and (3) difficulty navigating a complex, decentralized health system. Conclusion: Systemic changes are needed to reduce pregnant and parenting women's barriers to seeking medication for opioid use disorder. These include improved childcare support at both in-patient and outpatient treatment programs, which would assuage women's barriers related to childcare, as well as their fears of losing access to their children if they spend time away from their children for treatment. An additional systemic improvement that may reduce barriers for these women is access to comprehensive, integrated care for their prenatal care, postpartum care, pediatric appointments, and appropriate substance use disorder treatment. Plain language summary: Pregnancy and parenting-related barriers to receiving medication for opioid use disorder: Interview themes from multiple perspectives Women face unique barriers when seeking treatment for substance use disorders, often related to pregnancy and parenting. This study used one-on-one interviews to learn more about the pregnancy- and parenting-related barriers women face when initiating or continuing medication for opioid use disorder, specifically. Three different groups were interviewed: women with current or past opioid use disorders who have used or were presently using medication for opioid use disorder, professionals working in substance use disorder treatment programs, and criminal justice professionals (N = 42). Three parenting-related themes emerged from the interviews: (1) insufficient access to childcare to navigate appointments and meetings, (2) fear of losing custody of, or access to, one's children, and (3) prioritizing one's children's needs before one's own. Three pregnancy-related themes emerged from the interviews: (1) hesitancy among physicians to prescribe medication for opioid use disorder for pregnant patients, (2) limited access to resources in rural areas, and (3) difficulty navigating a complex health system. Systemic changes are needed to reduce pregnant and parenting women's barriers to seeking medication for opioid use disorder. These include improved childcare support at treatment programs, which would assuage women's barriers related to childcare, as well as their fears of losing access to their children if they spend time away from their children for treatment. An additional systemic improvement that may reduce barriers for these women is access to comprehensive, integrated care for their prenatal care, postpartum care, pediatric appointments, and appropriate substance use disorder treatment. [ABSTRACT FROM AUTHOR]

The article focuses on treatments for unipolar major depressive disorder (MDD) and attention-deficit/hyperactivity disorder (ADHD). Topics discussed include the first step in the treatment of patients with depression and with partial or no response to current treatments, novel agents for the treatment of MDD, and disorders in clinical trials assessing the benefits of psilocybin.

Background: As opioid overdoses continue rising, interventions are needed to expand naloxone carriage, an opioid overdose reversal agent. Use of fentanyl test strips (FTS) might promote naloxone carriage. This study examines the relationship between FTS use, perceived overdose risk, and naloxone carriage in Wisconsin, United States. Methods: In a survey of people who use drugs (n = 341) in southern Wisconsin, respondents were asked about FTS use, perceived overdose risk, and how often they (1) have naloxone, (2) have more than one dose of naloxone, and (3) the number of naloxone doses possessed currently. Likert responses were mapped to an integer scale. Ordinal and linear multivariable regression examined the relationship between FTS use and study outcomes while adjusting for respondent characteristics. Results: Most respondents were male (59.6%), identified heroin as their drug of choice (70.7%) and reported intravenous use (87.9%). In unadjusted models, FTS use was associated with more often having naloxone (OR: 2.10; p = 0.005), more often having multiple naloxone doses (OR: 2.98; p < 0.001), and possessing a greater number of naloxone doses (dose count difference: 2.85; p = 0.001). In adjusted models, FTS use was associated with more often having multiple naloxone doses (OR: 2.29; p = 0.005) and possessing a greater number of naloxone doses (dose count difference: 2.25, p = 0.020). Conclusions: Individuals who use FTS more often carry multiple doses relative to individuals who do not use FTS. Given that naloxone carriage is critical for reducing opioid overdose risk, expanding FTS use may offer a strategy to reduce opioid overdose rates via improved naloxone carriage. [ABSTRACT FROM AUTHOR]

We sought to characterize overdose and non-overdose mortality among PLWH amidst the illicit drug toxicity crisis in British Columbia, Canada. A population-based analysis of PLWH (age ≥19) in British Columbia accessing healthcare from April 1996 to March 2017 was conducted using data from the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort linkage. Underlying causes of deaths were stratified into overdose and non-overdose causes. We compared (bivariate analysis) health-related characteristics and prescription history between PLWH died of overdose and non-overdose causes between April 2009 and March 2017. Among 9,180 PLWH, we observed 962 deaths (142 [14.7%] overdoses; 820 [85.2%] other causes). Compared to those who died from other causes, those who died of overdose were significantly younger (median age [Q, Q3]: 46 years [42, 52] vs. 54 years [48, 63]); had an indication of chronic pain (35.9% vs. 27.1%) and hepatitis C virus (64.8% vs. 50.4%), but fewer experienced hospitalization in the year before death. PLWH who died were most likely to be prescribed with opioids (>50%) and least likely with opioid agonist therapy (<10%) in a year before death. These findings highlight the syndemic of substance use, HCV, and chronic pain, and how the crisis is unqiuely impacting females and younger people. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). Design: This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP‐NX) and extended‐release naltrexone (XR‐NTX). Setting: Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. Participants: A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non‐Hispanic White. Measurements The primary outcome was first self‐reported day of non‐prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time‐line follow‐back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self‐reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. Findings Forty‐seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80–12.50, P < 0.001] and over a 7‐day period (aHR = 1.27 for each additional day, CI = 1.18–1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05–5.39, P = 0.044). Conclusions: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non‐prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended‐release naltrexone. [ABSTRACT FROM AUTHOR]

Introduction: Peripherally acting μ -opioid receptor antagonists (PAMORAs) are used in the treatment of opioid induced constipation without impacting the actions of opioid analgesics. Subcutaneous methylnaltrexone was one of the first PAMORAs approved in April 2008 for the treatment of opioid induced constipation in adult patients. The safety and effectiveness of methylnaltrexone has not been established in pediatric patients. In this study, the use of subcutaneous methylnaltrexone in pediatric patients is analyzed and reviewed. The primary outcome is occurrence of a bowel movement within 24 h after methylnaltrexone (MNTX) administration and the number of bowel movements following treatment with methylnaltrexone. Secondary outcomes include safety in this patient cohort. Methods: This is a retrospective study of 79 pediatric patients with opioid induced constipation. Patients were administered methylnaltrexone during their inpatient stay. Data on bowel activity after methylnaltrexone was obtained from the hospital information system. Results: Out of the 79 patients who received methylnaltrexone, there were seven patients from whom data could not be analyzed. Of the 72 patients whose data was available, 38% (N = 27) were documented as having a bowel movement, 62% (N = 45) did not have a bowel movement. Reported adverse events were minimal with nausea (N = 3), vomiting (N = 1), and flatulence (N = 6). Conclusion: Methylnaltrexone appears safe in the pediatric population and produces bowel movements in more than a third of pediatric patients. It is a feasible and safe option for opioid induced constipation in pediatric patients. [ABSTRACT FROM AUTHOR]

Sex differences may exist in opioid use disorder (OUD) treatment. This study examined the treatment effects of buprenorphine/naloxone (BUP/NX) and methadone (MET) on the Clinical Opiate Withdrawal Scale (COWS) score in individuals with OUD and tested whether the associations differ by sex. We performed a secondary analysis of the data from the National Drug Abuse Treatment Clinical Trials Network (CTN) protocol-0027. A total of 1269 participants (861 males and 408 females) being aged 18 or older with OUD were randomly assigned to receive BUP/NX (n = 740) or MET (n = 529). The paired t test was initially used to compare the COWS scores between pre-dose and post-dose for BUP/NX and MET treatments, separately. The linear mixed model was used to examine the changes in COWS score adjusted for baseline demographic, substance use, and mental health disorders. The interaction of sex and treatment was detected and stratified analysis by sex was conducted. The paired t test showed that both BUP/NX and MET treatments significantly reduced the COWS scores (p values <0.0001). BUP/NX revealed higher COWS scores than MET (p = 0.0008) and females demonstrated significantly higher COWS scores than males (p = 0.0169). Stratified by sex, BUP/NX compared with MET revealed higher COWS scores only in males (p = 0.0043), whereas baseline amphetamines use disorder and major depressive disorder were significantly associated with COWS scores in females (p = 0.0158 and 0.0422, respectively). Both BUP/NX and MET are effective in decreasing opioid withdrawal symptoms via COWS scores, however, treatment plans for OUD by clinical providers should consider sex differences. [ABSTRACT FROM AUTHOR]

Objectives: Some states, including Massachusetts, require automatic filing of child abuse and neglect for substance-exposed newborns, including infants exposed in-utero to clinician-prescribed medications to treat opioid use disorder (MOUD). The aim of this article is to explore effects of these mandated reporting policies on pregnant and postpartum people receiving MOUD. Methods: We used modified grounded research theory, literature findings, and constant comparative methods to extract, analyze and contextualize perinatal experiences with child protection systems (CPS) and explore the impact of the Massachusetts mandated reporting policy on healthcare experiences and OUD treatment decisions. We drew from 26 semi-structured interviews originally conducted within a parent study of perinatal MOUD use in pregnancy and the postpartum period. Results: Three themes unique to CPS reporting policies and involvement emerged. First, mothers who received MOUD during pregnancy identified mandated reporting for prenatally prescribed medication utilization as unjust and stigmatizing. Second, the stress caused by an impending CPS filing at delivery and the realities of CPS surveillance and involvement after filing were both perceived as harmful to family health and wellbeing. Finally, pregnant and postpartum individuals with OUD felt pressure to make medical decisions in a complex environment in which medical recommendations and the requirements of CPS agencies often compete. Conclusions for Practice: Uncoupling of OUD treatment decisions in the perinatal period from mandated CPS reporting at time of delivery is essential. The primary focus for families affected by OUD must shift from surveillance and stigma to evidence-based treatment and access to supportive services and resources. Significance: What is already known on this subject? Child protection systems (CPS) reporting is associated with barriers to prenatal care and family resources and services. Some state policies in the United States mandate reporting to CPS for prenatal substance exposure, including prescribed medications for opioid use disorder. What this study adds? This study centers the experiences of pregnant and postpartum people with opioid use disorder with mandated reporting policies for prenatal substance exposure, describes the harms to families associated with these policies, and makes recommendations for policy change. Findings emphasize the need to uncouple medical decisions from CPS reporting and involvement. [ABSTRACT FROM AUTHOR]

People who use substances (PWUS) (e.g. inject substances) are at risk of many harms. Various services help reduce risks including drug treatment programs such as withdrawal management and opioid agonist treatment. Much of the research on PWUS' experiences of treatment programs is set in large urban centers creating a knowledge gap of experiences in other places. Our study helps address this gap by exploring PWUS' experiences of treatment programs in Atlantic Canada which is a region with many small urban centers and rural areas. One-on-one qualitative interviews were conducted with 55 PWUS focusing on their experiences of treatment program facilitators (or what helped with access and retention), and/or barriers to treatment access and retention (or what was not helpful). Data were analyzed for key themes/subthemes and organized using a slightly modified Rhodes' risk environment framework. PWUS' experiences of facilitators and barriers cross all four environments of treatment programs: policy and practice, physical, social, and resource environments. For some PWUS, barriers impacted their access to or retention in treatment, and hence are of serious concern given the current toxic illicit drug supply in Canada. Several barriers are shaped by drug criminalization and thus this research points to the need for decriminalization to help reduce barriers. [ABSTRACT FROM AUTHOR]

Buprenorphine is increasingly used to treat pain in patients with sickle cell disease but optimal timing and approach for transitioning patients from full agonist opioids to buprenorphine is unknown. We present the case of a 22-year-old woman with sickle cell disease and acute on chronic pain who transitioned from high-dose oxycodone to buprenorphine/naloxone during a hospital stay for vaso-occlusive episode. Utilizing a microdosing approach to minimize pain and withdrawal, buprenorphine/naloxone was gradually uptitrated while she received full agonist opioids. During the transition, she experienced some withdrawal in the setting of swallowed buprenorphine/naloxone tablets, which were intended to be dosed sublingually. Nevertheless, the transition was tolerable to the patient and her pain and function significantly improved with buprenorphine treatment. This case also highlights the challenges and unique considerations that arise when providing care for the hospitalized patient who is also incarcerated.

Background: The current epidemic of opioid overdoses in the United States necessitates a robust public health and clinical response. We described patterns of non-fatal opioid overdoses (NFOODs) in a small western region using data from the 9-1-1 Computer Assisted Dispatch (CAD) record and electronic Patient Clinical Records (ePCR) completed by EMS responders. We determined whether CAD and ePCR variables could identify NFOOD cases in 9-1-1 data for intervention and surveillance efforts. Methods: We conducted a retrospective analysis of 1 year of 9-1-1 emergency medical CAD and ePCR (including naloxone administration) data from the sole EMS provider in the response area. Cases were identified based on clinician review of the ePCR, and categorized as definitive NFOOD, probable NFOOD, or non-OOD. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the most prevalent CAD and ePCR variables were calculated. We used a machine learning technique-Random-Forests (RF) modeling-to optimize our ability to accurately predict NFOOD cases within census blocks. Results: Of 37,960 9-1-1 calls, clinical review identified 158 NFOOD cases (0.4%), of which 123 (77.8%) were definitive and 35 (22.2%) were probable cases. Overall, 106 (67.1%) received naloxone from the EMS responder at the scene. As a predictor of NFOOD, naloxone administration by paramedics had 67.1% sensitivity, 99.6% specificity, 44% PPV, and 99.9% NPV. Using CAD variables alone achieved a sensitivity of 36.7% and specificity of 99.7%. Combining ePCR variables with CAD variables increased the diagnostic accuracy with the best RF model yielding 75.9% sensitivity, 99.9% specificity, 71.4% PPV, and 99.9% NPV. Conclusion: CAD problem type variables and naloxone administration, used alone or in combination, had sub-optimal predictive accuracy. However, a Random Forests modeling approach improved accuracy of identification, which could foster improved surveillance and intervention efforts. We identified the set of NFOODs that EMS encountered in a year and may be useful for future surveillance efforts.

AimsTo investigate whether reduction in opioid use differs when treated by either buprenorphine-naloxone (BUP) or methadone (MET) among adults with comorbid opioid use disorder (OUD) and mental disorders.Design, setting and participantsIn a randomized controlled trial, adults with OUD were randomized to 24 weeks of either BUP or MET treatment and were followed up in 3-yearly assessments. The present secondary analyses were based on 597 participants who completed all assessments.MeasurementsThe outcome measure was the number of days of using opioids per month during the follow-up period. The Mini-International Neuropsychiatric Interview (MINI) was used to classify participants into three groups: life-time mood disorder (n = 302), life-time mental disorder other than mood disorder (n = 114) and no mental disorder (n = 181). Medication treatment (BUP, MET, no treatment) during the follow-up period was a time-varying predictor.FindingsBased on zero-inflated Poisson (ZIP) mixed regression analysis, it was found that relative to no treatment, opioid use during the follow-up was significantly reduced by BUP [odds ratio (OR) = 0.12, 95% confidence interval (CI) = 0.07-0.21 for any use; risk ratio (RR) = 0.77, 95% CI =0.66-0.89 for days of use] and by MET [OR = 0.33, 95% CI = 0.25-0.45 for any use; RR = 0.78, 95% CI = 0.72-0.84 for days of use]. Relative to MET, BUP was associated with a lower likelihood of any opioid use among participants with mood disorders (OR = 0.52, 95% CI = 0.36-0.74) and for participants without mental disorder (OR = 0.37, 95% CI = 0.21-0.66) and fewer number of days using opioids (RR = 0.37, 95% CI = 0.25-0.56) among participants with other mental disorders.ConclusionsAmong adults with comorbid opioid use disorder and mental disorders, treatment with buprenorphine-naloxone produced greater reductions in opioid use than treatment with methadone.

Research objectiveThe COVID-19 pandemic disrupted healthcare delivery worldwide with likely negative effects on people who use opioids (PWUO). This scoping review of the original research literature describes the impact of the COVID-19 pandemic on healthcare delivery for PWUO and identifies gaps in the literature.MethodsThis scoping review of the original research literature maps the available knowledge regarding the impact of the COVID-19 pandemic on healthcare delivery for PWUO. We utilized the methodology developed by the Joanna Briggs Institute for scoping reviews, and content analyses methodology to characterize the current state of the literature.ResultsOf the 14 included studies, administrative database (n = 11), cross-sectional (n = 1) or qualitative (n = 2) studies demonstrated service gaps (n = 7), patient/provider experiences (n = 3), and patient outcomes for PWUO (n = 4). In March 2020, healthcare utilization dropped quickly, sharply increasing only for reasons of opioid overdose by May 2020. Service gaps existed in accessing treatment for new patients during the pandemic due to capacity and infrastructure limits. Physicians reported difficulty referring patients to begin an outpatient opioid treatment program due to increased restrictions in capacity and infrastructure. Patients also reported uncertainty about accessing outpatient treatment, but that telehealth initiation of buprenorphine increased access to treatment from home. Disproportionate increases in overdose rates among African Americans were reported in two studies, with differences by race and gender not examined in most studies. Fatal overdoses increased 60% in African Americans during the pandemic, while fatal overdoses in Non-Hispanic White individuals decreased.ConclusionsIn summary, this beginning evidence demonstrates that despite early reluctance to use the healthcare system, opioid overdose-related use of healthcare increased throughout the pandemic. Service delivery for medications to treat OUD remained at or above pre-pandemic levels, indicating the ability of telehealth to meet demand. Yet, racial disparities that existed pre-pandemic for PWUO are intensifying, and targeted intervention for high-risk groups is warranted to prevent further mortality. As the pandemic progresses, future research must focus on identifying and supporting subgroups of PWUO who are at heightened risk for experiencing negative outcomes and lack of access to care.

In the first head‐to‐head study of nalmefene nasal spray (OPVEE is the trade name) vs. naloxone to reverse opioid overdose conducted in volunteers, researchers found that nalmefene worked faster than a 4 milligram (mg) dose of naloxone. It worked much faster, in fact, 2.7 mgs of OPVEE reversed respiratory depression within 5 minutes, compared to 20 minutes for 4 mgs of naloxone. The opioid that was given to the volunteers was remifentanil, a synthetic opioid. [ABSTRACT FROM AUTHOR]

There is a need to develop a novel analgesic for pain associated with interstitial cystitis/painful bladder syndrome (IC/PBS). The use of the conventional μ-opioid receptor agonists to manage IC/PBS pain is controversial due to adverse CNS effects. These effects are attenuated in benzylideneoxymorphone (BOM), a low-efficacy μ-opioid receptor agonist/δ-opioid receptor antagonist that attenuates thermal pain and is devoid of reinforcing effects. We hypothesize that BOM will inhibit bladder pain by attenuating responses of urinary bladder distension (UBD)-sensitive afferent fibers. Therefore, the effect of BOM was tested on responses of UBD-sensitive afferent fibers in L6 dorsal root from inflamed and non-inflamed bladder of rats. Immunohistochemical (IHC) examination reveals that following the induction of inflammation there were significant high expressions of μ, δ, and μ-δ heteromer receptors in DRG. BOM dose-dependently (1-10 mg/kg, i.v) attenuated mechanotransduction properties of these afferent fibers from inflamed but not from non-inflamed rats. In behavioral model of bladder pain, BOM significantly attenuated visceromotor responses (VMRs) to UBD only in inflamed group of rats when injected either systemically (10 mg/kg, i.v.) or locally into the bladder (0.1 ml of 10 mg/ml). Furthermore, oxymorphone (OXM), a high-efficacy μ-opioid receptor agonist, attenuated responses of mechanosensitive bladder afferent fibers and VMRs to UBD. Naloxone (10 mg/kg, i.v.) significantly reversed the inhibitory effects of BOM and OXM on responses of bladder afferent fibers and VMRs suggesting μ-opioid receptor-related analgesic effects of these compounds. The results reveal that a low-efficacy, bifunctional opioid-based compound can produce analgesia by attenuating mechanotransduction functions of afferent fibers innervating the urinary bladder.

ObjectivePharmacological treatments that can concomitantly address cigarette smoking and heavy drinking stand to improve health care delivery for these highly prevalent co-occurring conditions. This superiority trial compared the combination of varenicline and naltrexone against varenicline alone for smoking cessation and drinking reduction among heavy-drinking smokers.MethodsThis was a phase 2 randomized double-blind clinical trial. Participants (N=165) who were daily smokers and drank heavily received either 2 mg/day of varenicline plus 50 mg/day of naltrexone or 2 mg/day of varenicline plus matched placebo pills for 12 weeks. Primary outcomes were 7-day point prevalence of nicotine abstinence (bioverified by a breath CO reading ≤5 ppm) at the 26-week follow-up and number of drinks per drinking day during the 12-week treatment phase.ResultsSmoking abstinence at week 26 was significantly higher in the varenicline plus placebo condition than in the varenicline plus naltrexone condition (N=37 [45.1%] compared with N=22 [26.5%]). For drinks per drinking day, there was a medication effect favoring the combination of varenicline and naltrexone over varenicline alone across the 12-week treatment phase, although it did not meet the significance threshold.ConclusionsThese findings suggest that smoking cessation and drinking reduction can be concomitantly targeted with pharmacotherapy and that while varenicline alone may be sufficient as a smoking cessation aid in heavy-drinking smokers, the combination of varenicline and naltrexone may confer benefits with regard to drinking outcomes, particularly during the 12-week period of active medication treatment.

Background. Overdose deaths in the United States (U.S.) surpassed 100,000 in 2021. Problem-solving courts (PSCs), which originally began as drug courts, divert people with nonviolent felonies and underlying social issues (e.g. opioid use disorders (OUDs)) from the carceral system to a community-based treatment court program. PSCs are operated by a collaborative court staff team including a judge that supervises PSC clients, local court coordinators that manage PSC operations, among other staff. Based on staff recommendations, medications for opioid use disorders (MOUDs) can be integrated into court clients' treatment plans. MOUDs are an evidence-based treatment option. However, MOUDs remain widely underutilized within criminal justice settings partially due to negative perceptions of MOUDs held by staff. Objective. PSCs are an understudied justice setting where MOUD usage would be beneficial. This study sought to understand how court coordinators' perceptions and attitudes about MOUDs influenced their uptake and utilization in PSCs. Methods. A nationally representative survey of 849 local and 42 state PSC coordinators in the U.S. was conducted to understand how coordinators' perceptions influenced MOUD utilization. Results. Generally, court coordinators hold positive views of MOUDs, especially naltrexone. While state and local coordinators' views do not differ greatly, their stronger attitudes align with different aspects of and issues in PSCs such as medication diversion (i.e. misuse). Conclusions. This study has implications for PSCs and their staff, treatment providers, and other community supervision staff (e.g. probation/parole officers, court staff) who can promote and encourage the use of MOUDs by clients. [ABSTRACT FROM AUTHOR]

The co-occurrence of substance use disorders (SUD) and other mental disorders (OMD) is assumed to be high, but the details are uncertain in Spain. The objective of the present study was to know the prevalence of this comorbidity, as well as the pharmacological treatment, both in specific addiction treatment networks and in mental health networks, with a gender perspective. Observational, multicenter study, with a randomized sample, of patients under treatment for SUD or OMD in Spain (N = 1783). A specific questionnaire, collecting sociodemographic and clinical variables, diagnosed SUD and OMD, and prescribed psychotropic drugs, was completed by treating clinicians. Differences between females and males were searched. A high prevalence of OMD was found in those patients treated for their SUD (71%), and also of diagnoses of SUD (59%) in people treated for OMD. Significant relationships between addiction to certain substances and specific mental disorders were found (with no main differences between women and men). The treatments for OMD were very common in the addiction treatment networks, but that of SUDs in those patients treated in the mental health networks was less than expected. A high prescription of benzodiazepines was found. Women were less frequently diagnosed with cannabis, opioid, and especially cocaine use disorders, and they had fewer psychotic disorders and more affective, anxiety, sleep, and eating disorders, with the rest being the same, including personality disorders. Women had fewer treatments with agonists and more with antagonists, and more prescriptions of anxiolytics and antidepressants. This study provides preliminary information on the coexistence in routine clinical practice of addictive disorders and other mental disorders in Spain, and on the treatment provided, and shows differences in prevalence and clinical characteristics, and especially in treatment approaches between women and men. Thus, should be useful to adapt the treatment response with greater precision, and with a gender perspective. [ABSTRACT FROM AUTHOR]

Naloxone is a non-selective opiate receptor antagonist that is mainly used in the management of acute opioid overdose or intoxication. Previously, naloxone has been shown to have anti-inflammatory and antioxidant properties. Concanavalin A (Con A) model is a common and well established animal model of autoimmune hepatitis that closely resembles the pathological alterations that occur in human. The present study demonstrates that a low dose of naloxone (LD NX) has the ability to improve hepatic function and attenuate hepatic damage induced by Con A as indicated by a clear reduction in serum aminotransferase, bilirubin and enhancement of albumin production as well as liver pathological changes. Also, The proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interferon- γ (IFN-γ), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were highly suppressed in animals pretreated with LD NX via interference with TLR4/NF-κB as well as JNK signaling pathways. Furthermore, oxidative stress was highly attenuated in animals pretreated with LD NX as indicated by high reduction in hepatic MDA and an increase in Nrf2, HO-1 expression and subsequent production of the endogenous antioxidants, SOD, CAT and GSH. Collectively, this study demonstrates that LD NX has the ability to mitigate Con A-induced autoimmune hepatitis via modulation of inflammatory cytokines secretion and interference with reactive oxygen species generation. [ABSTRACT FROM AUTHOR]

Introduction: Posterior reversible encephalopathy syndrome is a clinical and imaging syndrome characterized by endothelial dysfunction, blood–brain barrier disruption, and vasogenic edema. The common clinical symptoms of posterior reversible encephalopathy syndrome include headache, altered consciousness, visual disturbances, and seizures, among which headache and seizures are the most common. The classic imaging patterns usually reveal vasogenic edema. Case Report: We describe the case of a middle-aged woman with gastric cancer. She was under treatment by fluorouracil, leucovorin, oxaliplatin, and docetaxel regimen and thrombocytopenia regimen after tumor progression, but developed unconsciousness, irritability, and headache shortly after initiation of treatment. Her magnetic resonance imaging in our hospital shows abnormal signals in bilateral frontal parietal occipital lobes with hyperintensities on T2-weighted magnetic resonance imaging and fluid-attenuated inversion recovery imaging, accompanied by the increased value of apparent diffusion coefficient. And T1-weighted images illustrate hypointense foci, with increased diffusion-weighted imaging signals. Management and Outcome: After admission, she was treated to control blood pressure, reduce brain edema, expand blood vessels, improve consciousness, and symptomatic support treatment. 3 days after the onset of the disease, her headache symptoms and state of consciousness gradually improved, and her blood pressure can be controlled at about 130/80 mmHg. Discussion: This is the first report that posterior reversible encephalopathy syndrome is caused by a thrombocytopenia regimen, and our case highlights the pathogenic role of a thrombocytopenia regimen in posterior reversible encephalopathy syndrome. However, the association between the thrombocytopenia regimen and previous fluorouracil, leucovorin, oxaliplatin, and docetaxel regimens needs further study. [ABSTRACT FROM AUTHOR]