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Background: The present study aimed to investigate the effect of pre-admission Opioid Use Disorder (OUD) on in-hospital mortality and 6-month follow-up TBI outcomes. Design: This study included 2804 patients with TBI admitted to the Intensive Care Unit of Emtiaz (Rajaee) Hospital, a referral trauma center in Shiraz, Iran. Finally, 1087 eligible participants were selected from included patients. Then, 872 discharged patients were followed for six months. Subsequently, unfavorable neurological outcomes (Glasgow Outcome Scale-Extended ≤ 4) and the mortality rate were compared among the patients with and without OUD. Results: The mean age of the patients was 38.0 ± 18.9 years old (84.7% men). About 9.2% of patients had OUD. Opioid users had a slightly lower risk of in-hospital mortality (OR = 0.62, 95% CI = [0.328, 1.183], P-value = 0.148). In contrast, 6-month follow-up mortality significantly increased in the survived patients with a history of pre-admission OUD (OR = 2.49, 95%CI= [1.29, 2.80], P-value = 0.007). Moreover, 6-month unfavorable outcomes were raised in OUD, though it was not significant (OR = 1.59, 95%CI= [0.89, 2.84], P-value = 0.121). Conclusions: Our results revealed that patients with OUD are at increased risk of 6-month follow-up complications and also death following moderate to severe TBI. Although OUD decreased in-hospital mortality, 6-month follow-up indicated that mortality and unfavorable outcomes were increased in the OUD group. Based on the existing evidence, this effect is probably not only due to the destructive impact of pre-admission OUD on brain physiology. However, it may also be due to an increase in opioid consumption to alleviate pain and withdrawal symptoms after hospital discharge. [ABSTRACT FROM AUTHOR]

Background: Substance misuse is common among cancer survivors and can negatively impact cancer outcomes. Methods: We conducted a cross-sectional study using National Survey on Drug Use and Health data for 2015 to 2020. We included adult respondents with a history of solid tumor cancer. We calculated the weighted prevalence and corresponding SEs (both expressed as percentages) of substance (alcohol, opioid, sedative, stimulant, other) misuse for respondents with any history of solid tumor cancer and, in secondary analyses, respondents diagnosed with cancer in the prior 12 months. Results: The study included 6,101 respondents with any history of cancer, 1,437 diagnosed in the prior 12 months. Alcohol was the most commonly misused substance. The average prevalence of alcohol misuse was 14.4% (SE 0.60%) across cancer types; it was markedly more common among people with a history or cervical (24.2% [3.0%]) or head and neck cancer (27.4% [7.1%]). The next most common form of substance misuse was opioid misuse (average prevalence: 2.7% [0.25%]). As with alcohol misuse, the prevalence of opioid misuse was higher among those with a lifetime history of cervical cancer (5% [1%]) or head and neck cancer (5% [3%]). Results were generally consistent among cancer survivors diagnosed in the prior 12 months. Conclusions: There is a clear opportunity to address substance misuse—particularly alcohol misuse—among cancer survivors. Such efforts should focus on populations with a high prevalence of substance misuse (e.g., cervical and head and neck cancer survivors) and have strong potential to improve cancer-specific and overall health outcomes. [ABSTRACT FROM AUTHOR]

Integrated behavioral healthcare interventions have increased access to care for people with behavioral health conditions in primary care settings. However, they have not been widely implemented in low-barrier HIV care settings where undertreated behavioral health needs remain high. We conducted a formative qualitative evaluation, using in-depth interviews with purposively selected stakeholders (n = 13) and patients (n = 16), to identify anticipated barriers and facilitators to integrating care for depression and opioid use disorder for people with HIV via the Collaborative Care Model at a low-barrier HIV clinic. Patients and stakeholders expressed their enthusiasm for the Collaborative Care Model based on its perceived relative advantage over the standard of care referral system. Availability of resources, practical concerns about perceived fit with low-barrier HIV care, and anticipated suitability given other behavioral health comorbidities and patients’ complex socioeconomic needs partially tempered stakeholder perceptions of appropriateness for the Collaborative Care Model. Patients and service delivery stakeholders were receptive to the Collaborative Care Model, but felt it was moderately appropriate in the context of low-barrier HIV care, which necessitated key adaptations to core model components to improve its contextual fit. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsAlthough medications for opioid use disorder (MOUD) are effective for treating opioid use disorder (OUD), persistent barriers still prevent patients from accessing this life-saving care. Policies to increase MOUD access have produced suboptimal results. This study presents a qualitative system dynamics model that elucidates the complexities of accessing and staying in MOUD treatment.We utilized a community-based system dynamics approach to modeling the MOUD treatment system. We engaged a cohort of system experts/stakeholders, including individuals who had received MOUD, treatment providers, and policymakers, in interviews and group model building to develop and refine a simulation model. We then created a qualitative causal loop diagram based on insights gained while developing the simulation model and a review of interview transcripts.The causal loop diagram captures four key factors affecting treatment initiation, retention, and leaving: (1) fraught interactions between patients and healthcare providers; (2) stigma-driven regulation of MOUD creating a culture of fear and defensive medicine; (3) a punitive culture in clinics and opioid treatment programs offering MOUD; and (4) the internalization of the abstinence narrative contributing to premature termination of treatment.Our analysis highlights how interdependent and non-linear feedback processes diminish or counteract the effectiveness and sustainability of MOUD policy interventions. Due to system memory and cultural resistance to change, even rolling back reactionary policies may do little to curb established behavioral patterns. In addition, conflicting and competing strategies among various actors within the system contribute to goal misalignment and a lack of standardization of care. [ABSTRACT FROM AUTHOR]

Alcohol misuse is common in persons on opioid agonist maintenance treatment (OAMT). We tested the efficacy of screening and brief intervention (SBI) for harmful/hazardous alcohol use in buprenorphine/naloxone (BNX)-assisted OAMT. It was a double-blind, parallel-group, randomized trial, where 150 participants with alcohol misuse (Alcohol Use Disorder Identification Test – AUDIT 8–19) on BNX were allocated equally to receive either a single session SBI or screening and brief advice (control). Participants were followed up at three months. The primary outcome was the change in AUDIT; other outcomes were risk transition, change in the frequency of heavy drinking, days of abstinence from alcohol, Gamma-glutamyl transferase (GGT) levels, non-prescription opioid use, and adherence to BNX. Follow-up data was gathered from 138 participants. SBI participants had a higher reduction in AUDIT scores at the follow-up (F = 129. 173, df = 1, p < .001, ηp2 =.469). A higher proportion of participants transitioned to a low-risk category in the SBI group. The SBI group showed a higher reduction in heavy drinking and days of alcohol abstinence. Although the proportion of persons with normal serum GGT increased in both groups, the difference was not significant at the follow-up. The SBI group performed better in non-prescription opioid use and BNX adherence. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fentanyl was administered at dark onset and sleep-wakefulness (S-W) was examined. • Fentanyl administration significantly increased wakefulness for the first 6 h. • This initial increase in wakefulness was followed by a rebound sleep for next 6 h. • Sulpiride was injected in the accumbal core before fentanyl and S-W was examined. • D2R blockade by sulpiride in the core attenuated the effects of fentanyl on S-W. Fentanyl, a potent analgesic and addictive substance, significantly impacts sleep-wakefulness (S-W). Acutely, it promotes wake, whereas chronic abuse leads to severe sleep disruptions, including insomnia, which contributes to opioid use disorders (OUD), a chronic brain disease characterized by compulsive opioid use and harmful consequences. Although the critical association between sleep disruptions and fentanyl addiction is acknowledged, the precise mechanisms through which fentanyl influences sleep remain elusive. Recent studies highlight the role of the dopaminergic system of the nucleus accumbens (NAc) in S-W regulation, but its specific involvement in mediating fentanyl's effects on S-W remains unexplored. We hypothesized that dopamine D2 receptors mediate fentanyl-induced effects on S-W. To test this hypothesis, male C57BL/6J mice, instrumented with sleep recording electrodes and bilateral guide cannulas above the accumbal core region (NAcC), were utilized in this study. At dark onset, animals were bilaterally administered sulpiride (D2 receptors antagonist; 250 ng/side) in the NAcC followed by an intraperitoneal injection of fentanyl (1.2 mg/Kg). S-W was examined for the next 12 h. We found that systemic administration of fentanyl significantly increased wakefulness during the first 6 h of the dark which was followed by a significant increase in NREM and REM sleep during the second 6 h of the dark period. D2-receptor blockade significantly reduced this effect as evidenced by a significant reduction in fentanyl-induced wakefulness during first 6 h of dark period and sleep rebound during the second 6 h. Our findings suggest that D2 receptors in the NAcC plays a vital role in mediating the fentanyl-induced changes in S-W. [ABSTRACT FROM AUTHOR]

Few evidence-based interventions have been widely adopted in common clinical settings, particularly for opioid-dependent people with HIV (PWH) seeking drug treatment. We developed a brief evidence-based intervention, Holistic Health for HIV (3H+), specifically for ease of implementation and integration within drug treatment settings. In this study, we compared 3H+ to the gold standard, Holistic Health Recovery Program (HHRP+) using a non-inferiority trial. Between 2012 and 2017, 106 participants were randomly assigned to either the brief 3H+ intervention or the gold standard HHRP+. HIV treatment (ART adherence, viral suppression) and risk behaviors (sharing injection equipment, condom use) were compared between the two arms at baseline, end-of-intervention (EOI-12 weeks) and at follow-up (24 weeks). Average treatment effect was calculated based on the difference-in-difference (DID) estimator and a non-parametric bootstrap was used to assess non-inferiority. At the 12-week EOI point, 3H+ was found to be non-inferior to HHRP+ with respect to multiple outcomes: percent sharing syringes and needles (DID:1.4, 95%CI [-18.6,21.5], p<0.01) and attainment of high ART adherence (DID: 9.7, 95%CI: [-13.1, 32.2], p = 0.04). At the 24-week EOI point, 3H+ was found to be non-inferior to HHRP+ with respect to percent sharing syringes and needles (DID: 8.9, [-10.1, 28.30], p = 0.04) and attainment of viral suppression (DID: 18.9, 95% CI:[-7.1, 42.0], p = 0.01). For other indicators, such as consistent condom use, the hypothesis test for non-inferiority was inconclusive at the 12-week EOI (DID: -20.2, 95%CI [-48.9–10.7], p = 0.51). For HIV treatment as prevention to be effective, PWH need to achieve viral suppression. In the absence of this success, they must reduce HIV risk behaviors. The finding that 3H+ was non-inferior to HHRP+ suggests that brief behavioral interventions can be deployed in real world settings to help more efficiently achieve Ending the HIV Epidemic goals. [ABSTRACT FROM AUTHOR]

Objective: There is a rising effort for hospital emergency departments (EDs) to offer and expand substance use disorder (SUD) services. This state-wide evaluation studies SUD services offered along the continuum of implementation across Kentucky's EDs to inform future state efforts to build ED bridge programs. Methods: We conducted a mixed-methods study using an online survey of all Kentucky Emergency Department Directors between January and May of 2023. We created a hospital-level dataset which we used to summarize quantitative questions and thematically analyze open-ended responses. Results: Our sample included 85 unique respondents (89% of all eligible Kentucky hospitals). Nine (11%) had active bridge programs to initiate opioid use disorder patients on buprenorphine. Respondents reported that the most challenging SUD-related services for EDs to implement were buprenorphine induction for opioid use disorder treatment (n = 36, 42%), referrals to community-based providers (n = 34, 40%), and providing social work services (n = 25, 29%). Respondents noted that the implementation and improvement of screening protocols were needed to better identify patients with SUD, expressed concerns about care continuity, and explicitly conveyed the need and desire for additional supports to provide SUD care. Conclusions: The landscape of Kentucky's ED SUD supports shows several hospitals that offer services along the continuum of SUD care, and highlights the importance of technical assistance and financial resources to ensure the continuum is broadly available. Kentucky's experience speaks to broader national challenges in supporting SUD in EDs – specifically the need for financial resources, buy-in and education, and creating referral relationships to ensure care continuity. [ABSTRACT FROM AUTHOR]

Introduction: Opioid drugs are potent analgesics that mimic the endogenous opioid peptides, endorphins and enkephalins, by activating the µ-opioid receptor. Opioid use is limited by side effects, including significant risk of opioid use disorder. Improvement of the effect/side effect profile of opioid medications is a key pursuit of opioid research, yet there is no consensus on how to achieve this goal. One hypothesis is that the degree of arrestin-3 recruitment to the µ-opioid receptor impacts therapeutic utility. However, it is not clear whether increased or decreased interaction of the µ-opioid receptor with arrestin-3 would reduce compulsive drug-seeking. Methods: We utilized three genotypes of mice with varying abilities to recruit arrestin-3 to the µ-opioid receptor in response to morphine in a novel longitudinal operant self-administration model. We also created a quantitative method to define compulsivity in drug-seeking based on a multi-variate analysis of several operant response variables. Results: We demonstrate that arrestin-3 knockout and wild type mice have highly variable drug-seeking behavior with few genotype differences. In contrast, in mice where the µ-opioid receptor strongly recruits arrestin-3, drug-seeking behavior is much less varied. We found that mice lacking arrestin-3 were more likely to meet the criteria for compulsivity whereas mice with enhanced arrestin-3 recruitment did not develop a compulsive phenotype. Conclusion: These experiments show that a lack of arrestin-3 is not protective against the abuse liability of morphine in an operant self-administration context. Our data also suggest that opioids that engage both G protein and arrestin-3, recapitulating the endogenous signaling pattern, will reduce abuse liability. [ABSTRACT FROM AUTHOR]

\nIntroduction: The treatment efficacy of extended-release naltrexone (XR-NTX) for opioid use disorder (OUD) has been demonstrated in several studies, but not in naturalistic settings where opioid agonist treatment (OAT) is freely accessible. This study aimed to examine the different treatment outcomes of XR-NTX in a setting where the participants freely chose XR-NTX as a treatment option instead of OAT. Methods: This was a 24-week open-label clinical prospective cohort study conducted in an outpatient setting at five hospitals in Norway. The study included 161 participants aged 18–65 years with OUD. Intramuscular injections of XR-NTX were administered every 4 weeks for 24 weeks. Measurements included retention in treatment, reasons for treatment discontinuation, days of use of opioids, other illicit substances and alcohol, level of heroin craving, treatment satisfaction, and adverse events (AEs). Results: Of 161 included participants, the mean age was 38 years, and 24% were women; 138 received at least one dose of the study medication (modified intention-to-treat [MITT] population), and mean time in treatment was 18.1 weeks (95% CI: 16.8–19.4). The majority of the MITT population (84; 60.9%) completed 24 weeks of treatment in the study. There was a significant decrease in the overall use of opioids (p < 0.001) and the use of alcohol, and other illicit substances were low. The participants generally reported high treatment satisfaction and low heroin cravings. Those who completed the 24 weeks of treatment reported significantly fewer days of opioid use (p < 0.001) and higher treatment satisfaction (p < 0.001) than those who discontinued treatment before 24 weeks. No serious AEs were directly related to XR-NTX use. Conclusion: This study demonstrated high retention rates, decreased opioid use, and low use of other illicit substances and alcohol. Participants also reported low cravings for heroin and high treatment satisfaction. Completion of the full 24-week treatment resulted in lower opioid use and increased treatment satisfaction compared to those who discontinued treatment before 24 weeks. The observed higher retention and reduced opioid use, compared to other studies, may be attributed to participants’ strong motivation for opioid abstinence facilitated by XR-NTX treatment. This study looked at the effectiveness of a drug called extended-release naltrexone (XR-NTX) for treating opioid addiction. The study was conducted in Norway, where patients could freely choose this treatment over other options. The study lasted 24 weeks and involved 161 participants aged 18–65 years. The participants were given injections of XR-NTX every 4 weeks. The researchers measured how long the participants stayed in treatment; their use of opioids, alcohol, and other drugs; their cravings for heroin; their satisfaction with the treatment; and any side effects. The results showed that most participants (about 61%) completed the full 24 weeks of treatment. There was a significant decrease in opioid use, and the use of alcohol and other drugs was low. The participants reported high satisfaction with the treatment and low cravings for heroin. Those who completed the full treatment used fewer opioids and were more satisfied with the treatment than those who stopped early. No serious side effects were directly related to XR-NTX use. In conclusion, the study found that XR-NTX treatment resulted in high retention rates, decreased opioid use, and low use of other drugs and alcohol. Participants also reported minimal cravings for heroin and high treatment satisfaction. Those who completed the full 24-week treatment had better outcomes than those who stopped early. This success may be due to the participants’ strong motivation to stop using opioids, facilitated by the XR-NTX treatment. [ABSTRACT FROM AUTHOR]

Background: Addiction medicine providers have a key role in HIV prevention amidst rising HIV incidence in persons who inject drugs (PWID). Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are vastly underutilized in this population. Inpatient hospitalization represents a potential touchpoint for initiation of HIV prophylaxis, though little research explores the role of addiction providers. Here we describe rates of PrEP/PEP delivery to hospitalized PWID seen by an Addiction Consult Service (ACS) at an urban, essential hospital. Methods: We performed a cross-sectional study of hospitalized patients who were seen by the ACS from January 1, 2020 to December 31, 2022 and had plausible injection drug use. We calculated the proportion of patients who received a new prescription for PrEP/PEP at discharge. We used descriptive statistics to characterize demographics, substance use, reason for admission, and indications for PrEP/PEP. Secondarily, we calculated the monthly proportion of all patients discharged from the hospital with PrEP/PEP who were seen by the ACS compared to those not seen by the ACS. Results: The average monthly proportion of ACS consults with plausible injection drug use who received PrEP/PEP was 6.4%. This increased from 4.2% in 2020 to 7.5% in 2022. Those seen by the ACS who received PrEP/PEP had high rates of opioid use disorder (97.5%), stimulant use disorder (77.8%), and homelessness (58.1%); over half were admitted for an injection-related infection. The indications for PrEP/PEP were injection drug use only (70.6%), followed by combined injection and sexual risk (20.2%); 71.9% of prescriptions were for PrEP and 28.1% for PEP. Overall, the ACS was involved in 83.9% of hospital-wide discharges with PrEP/PEP prescriptions (n = 242). Conclusions: PWID who were seen by the ACS received PrEP/PEP prescriptions at rates exceeding national averages. The ACS was also involved with the care of the majority of admitted patients who received PrEP/PEP at discharge. While PrEP/PEP use for PWID remains low, the inpatient ACS represents a key resource to improve uptake by leveraging the reachable moment of an inpatient hospitalization. [ABSTRACT FROM AUTHOR]

Opioid-seeking behaviors depend on glutamatergic plasticity in the nucleus accumbens core (NAcc). Here we investigated whether the behavioral and synaptic effects of opioids are influenced by acid-sensing ion channel 1A (ASIC1A). We tested the effects of ASIC1A on responses to several opioids and found that Asic1a−/− mice had elevated behavioral responses to acute opioid administration as well as opioid seeking behavior in conditioned place preference (CPP). Region-restricted restoration of ASIC1A in NAcc was sufficient to reduce opioid CPP, suggesting NAcc is an important site of action. We next tested the effects of oxycodone withdrawal on dendritic spines in NAcc. We found effects of oxycodone and ASIC1A that contrasted with changes previously described following cocaine withdrawal. Finally, we examined α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated and N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic currents in NAcc. Oxycodone withdrawal, like morphine withdrawal, increased the AMPAR/NMDAR ratio in Asic1a+/+ mice, whereas oxycodone withdrawal reduced the AMPAR/NMDAR ratio in Asic1a−/− mice. A single dose of oxycodone was sufficient to induce this paradoxical effect in Asic1a−/− mice, suggesting an increased sensitivity to oxycodone. We conclude that ASIC1A plays an important role in the behavioral and synaptic effects of opioids and may constitute a potential future target for developing novel therapies. [ABSTRACT FROM AUTHOR]

Introduction: Emergency medical services (EMS) systems are piloting interventions to respond to overdoses with additional services such as leave‐behind naloxone and medication for opioid use disorder, but little is known about the perspectives of people who use drugs (PWUD) on these interventions being delivered by EMS during an overdose response. Methods: The Consolidated Framework for Implementation Research guided the development of data collection tools, the analytic strategy and the organisation of results. A community engaged method was used which included both academically trained researchers and community trained researchers who are also PWUD. This study used semi‐structured interviews to gather data from 13 PWUD in King County, Washington in June 2022. Data were analysed using thematic analysis. Results: The people interviewed for this study viewed EMS distribution of leave‐behind naloxone and field‐based buprenorphine favourably. They viewed EMS facilitation of hepatitis C virus and HIV testing in the field less favourably and were concerned about stigmas associated with those results. Additional themes emerged regarding: the need for different approaches to post‐overdose care; the need for new services, including post‐overdose trauma counselling and an alternative destination to the emergency department; and the harms of law enforcement presence at overdose responses. Discussion and Conclusions: This study found strong support for leave‐behind naloxone and field‐initiated buprenorphine. Further training for EMS should include trauma‐informed care and strategies to address burnout and increase compassion. Alternatives to the emergency department as a post‐overdose destination are needed. These strategies should be considered by jurisdictions revising overdose response protocols. [ABSTRACT FROM AUTHOR]

Introduction: Inducting buprenorphine from methadone has traditionally involved initial opioid withdrawal, with risk of mental state deterioration in patients with serious mental illness (SMI). Micro‐dosing of buprenorphine, with small incremental doses, is a novel off‐label approach to transitioning from methadone and does not require a period of methadone abstinence. Given the limited literature about buprenorphine microdosing, we aimed to evaluate the feasibility and safety of inducting buprenorphine in a series of patients on methadone with SMI. Methods: For this retrospective case series, we reviewed the records of 16 patients with SMI at a Melbourne addiction treatment centre, from January 2021 to July 2022, who transitioned via micro‐dosing, from high‐dose methadone (>30 mg) to buprenorphine and depot‐buprenorphine. Psychiatric diagnoses, mental state, other substance withdrawal, transfer success, transition time, opioid withdrawal symptoms and overall patient experience were collected via objective and subjective reporting. Results: Methadone to buprenorphine transfer was completed by 88% of patients. Mental health measures remained stable with the exception of mildly increased anxiety. Median transfer time was 6.5 days for inpatients, 9 days for mixed setting and 10 days for outpatients. Most patients (93%) rated their experience 'manageable' reporting mild withdrawal symptoms. One patient met study criteria for precipitated withdrawal. Discussion and Conclusions: This retrospective case series provides evidence that the use of a micro‐dosing buprenorphine induction for methadone to buprenorphine transitions, including to depot‐buprenorphine, has negligible risk, is tolerated by patients with SMI and is unlikely to precipitate an exacerbation of their mental illness. [ABSTRACT FROM AUTHOR]

Introduction: There has been a significant increase in methamphetamine/amphetamine use in North America, particularly among people who use opioids. Despite its association with several negative health consequences, the population of people who use methamphetamine/amphetamine with opioids is not well characterised. The aim of this study was to investigate correlates of methamphetamine/amphetamine use among adults with prescription‐type opioid use disorder (POUD) starting methadone or buprenorphine/naloxone as part of a pragmatic randomised treatment trial in Canada. Methods: Multivariable logistic regression analyses were used to determine factors associated with baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) among participants of a pan‐Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take‐home dosing buprenorphine/naloxone models of care in people with POUD (e.g., licit or illicit, including fentanyl, prescribed or not). Results: The sample included 269 participants, of which 142 (52.8%) had positive baseline methamphetamine/amphetamine UDT. In the multivariable model, positive fentanyl UDT (adjusted odds ratio [AOR] 13.21, 95% confidence interval [CI] 6.45, 28.30), non‐fatal overdose in the last 6 months (AOR 2.26, CI 1.01, 5.17) and a lifetime history of opioid agonist therapy exposure prior to study entry (AOR 2.30, CI 1.09, 4.87) remained positively associated with baseline methamphetamine/amphetamine use. Discussion and Conclusions: In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including overdose risk. This suggests the need for targeted interventions to optimise treatment outcomes and prevent future overdoses in this population. Clinical Trial Registration: Available at: ClinicalTrials.gov NCT03033732. [ABSTRACT FROM AUTHOR]

The article discusses the comparison of 12-month prevalence estimates of substance use disorders using DSM-5 versus DSM-IV criteria among U.S. nonelderly adults with substance use. The study found that the shift from DSM-IV to DSM-5 criteria led to marked increases in the prevalence of common substance use disorders, with the addition of craving criteria explaining some of the increase. The findings suggest that a larger proportion of nonelderly adults may have substance use disorders than previously reported, highlighting the need for timely interventions. The study used data from the 2021 National Survey on Drug Use and Health and was sponsored by the National Institute on Drug Abuse. [Extracted from the article]

Aims: Methadone maintenance therapy (MMT) exhibits significant variability in pharmacokinetics and clinical response, partly due to genetic variations. However, data from sub‐Saharan African populations are lacking. We examined plasma methadone variability and pharmacogenetic influences among opioid‐addicted Tanzanian patients. Methods: Patients attending MMT clinics (n = 119) in Tanzania were genotyped for common functional variants of the CYP3A4, CYP3A5, CYP2A6, CYP2B6, CYP2C19, CYP2D6, ABCB1, UGT2B7 and SLCO1B1 genotypes. Trough plasma concentrations of total methadone, S‐methadone (S‐MTD) and R‐methadone (R‐MTD), with their respective metabolites, 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The methadone‐to‐EDDP metabolic ratio (MMR) was used to categorize the phenotype. Results: The proportions of MMR‐predicted ultrarapid, extensive, intermediate and slow methadone metabolizer phenotypes were 2.5%, 58.2%, 23.7% and 15.6%, respectively. CYP2B6 genotype significantly correlated with S‐methadone (P =.006), total methadone (P =.03), and dose‐normalized methadone plasma concentrations (P =.001). Metabolic ratios of R‐methadone (R‐MTD/R‐EDDP), S‐methadone (S‐MTD/S‐EDDP), and total methadone (MMR) were significantly higher among patients homozygous for defective variants (*6 or *18) than heterozygous or CYP2B6*1/*1 genotypes (P <.001). The metabolic ratio for S‐MTD and total methadone was significantly higher among ABCB1c.3435T/T than in the C/C genotype. No significant effect of CYP2D6, CYP2C19, CYP3A4, CYP3A5, CYP2A6, UGT2B7 and SLCO1B1 genotypes on S‐methadone, R‐methadone, or total methadone was observed. Conclusions: Approximately one in six opioid‐addicted Tanzanian patients are methadone slow metabolizers, influenced by genetic factors. Both the CYP2B6 and ABCB1 genotypes are strong predictors of methadone metabolic capacity and plasma exposure. Further investigation is needed to determine their predictive value for methadone treatment outcomes and to develop genotype‐based dosing algorithms for safe and effective therapy. [ABSTRACT FROM AUTHOR]

Introduction: In this perspective review, we evaluated the clinical management of fatal fentanyl overdose in several routes of administration, concentrating on both legally prescribed and illegally produced formulations. Methods: A literature search was conducted on Web of Science, PubMed, and Google Scholar databases, using the following keywords: fentanyl, illicit fentanyl, deaths, misuse, abuse, and naloxone. We included only articles whose abstracts were available in English. All articles were screened using their abstracts to determine their relevance to the current review. Results: The gold standard for treating both acute and chronic pain is fentanyl, but abuse of the drug has exploded globally since the late 2000s. Fentanyl abuse has been shown to frequently result in serious harm and even death. Conclusion: By educating patients and physicians, making rescue kits easily accessible, developing vaccines to prevent opioid addiction, and perhaps even creating new tamper-resistant fentanyl formulations, it may be possible to prevent fentanyl misuse, therapeutic errors, and the repercussions that follow. [ABSTRACT FROM AUTHOR]

Naltrexone, an opioid antagonist that blocks the reinforcing properties of opioid agonists, is often prescribed to preclude relapse to opioid use disorder (OUD) following detoxification. However, few laboratory studies have directly investigated the ability of naltrexone to alter relapse-inducing effects of opioid agonists, including their priming strength in reinstatement studies and their impact in brain regions known to be involved in drug-induced reinforcement in MRI studies. Here we directly address this issue by investigating the effects of continuous exposure to naltrexone on 1) fentanyl-induced reinstatement of drug-seeking behavior, 2) fentanyl-induced patterns of blood oxygenation level dependent (BOLD) activation in the nucleus accumbens (NAcc), and 3) fentanyl-induced changes in NAcc functional connectivity (FC) in awake non-human primates that are engaged in ongoing opioid self-administration studies. We found that naltrexone antagonizes the priming strength of fentanyl as shown by a rightward shift in its reinstatement dose–effect curve and that naltrexone surmountably antagonizes the BOLD response induced by fentanyl. However, while naltrexone also countered fentanyl's effects on NAcc FC, the effects were not surmounted by a higher dose of fentanyl. Together, these data suggest that, in contrast to naltrexone's modulation of fentanyl's effects on behavior and BOLD responses, their interactive effects on FC between multiple brain regions do not reflect their receptor-mediated activity. Additionally, we demonstrated opposing effects in the absence and presence of naltrexone on NAcc FC at baseline (i.e., in the absence of any fentanyl prime) suggesting that naltrexone alters FC at baseline, even though naltrexone appears behaviorally silent in the absence of an agonist prime. Together these data provide additional insight into ways in which naltrexone interacts with opioid agonists, both behaviorally and in the brain. Further understanding the effects of opioid agonists on patterns of FC could help elucidate our understanding of the neural processes that contribute to the initiation of and relapse to opioid-seeking behavior in OUD. [ABSTRACT FROM AUTHOR]

Objectives: The number of drug overdoses and drug-related deaths has increased across the United States in recent years. Reports of suspected opioid drug overdoses identified through emergency medical services (EMS) are valuable sources of information for shaping the public health response to drug overdoses. The objective of this study was to describe trends in the number of EMS-reported suspected opioid drug overdose events in South Carolina from 2019 through 2022. Methods: We included reports of suspected opioid drug overdoses if they met the definition of nonfatal opioid overdose syndrome in our analysis. We analyzed statewide data reported from EMS agencies to biospatial, Inc, from January 2019 through December 2022 to understand demographic trends for a statewide overdose and response program in South Carolina. Results: In 2022, a total of 11 078 suspected opioid drug overdose events, or 216.4 per 100 000 South Carolina residents, were reported by EMS. During the 4-year study period, the number of EMS-reported suspected opioid drug overdoses increased by 82%, with African American people experiencing a 133% increase and White people experiencing a 68% increase. The number of opioid overdoses increased among all age groups during the study period. Approximately 84% of opioid overdoses were reported in urban counties, but rural counties had a higher number of opioid overdose reports per capita than urban counties. Conclusions: Monitoring trends in suspected opioid drug overdoses allows decision makers to adjust resources and programs for overdose response and is essential for local coordinated response. Continued monitoring of trends is needed for an equitable response to prevent opioid drug overdoses. [ABSTRACT FROM AUTHOR]

Background and Objectives: Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription‐type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada. Methods: Secondary analysis of a pan‐Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take‐home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation). Results: Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60–3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32–3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p >.05). Conclusion and Scientific Significance: This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population. [ABSTRACT FROM AUTHOR]

This article discusses the controversy surrounding pre-operative opioid tapering and its potential to advance personalized, patient-centered pain medicine. The use of opioids for chronic non-cancer pain management is common, but it is associated with negative outcomes in the peri-operative period, such as respiratory failure and surgical site infections. The article presents the findings of a pilot study that assessed the feasibility of a pharmacist-led opioid tapering program before elective hip or knee arthroplasty. The study found high adherence to the program and positive outcomes in terms of physical functioning and quality of life. However, the study has limitations, and further research is needed to determine the effectiveness of pre-operative opioid tapering in a broader patient population. [Extracted from the article]

The purpose of this qualitative study is to assess facilitating factors and barriers for medications to treat opioid use disorder (MOUD) initiation among justice‐involved individuals in one rural Appalachian community, as well as how those factors may differ across the three types of Food and Drug Administration (FDA) approved medications. Qualitative interviews were conducted with rural justice‐involved individuals (N = 10) with a history of opioid use in the target community. Overall, participants demonstrated knowledge of the different types of MOUD and their pharmacological properties, but limited overall health literacy around opioid use disorder and MOUD treatment. Treatment access was hampered by transportation, time burdens, and costs. Findings call for research into improving health literacy education, training, and resources to decrease stigma and increase access to MOUD, particularly in light of the ongoing opioid crisis. State policies also need to increase access to all FDA medications among justice‐involved individuals, as well as supporting a care continuum from facility entry, release, and community re‐entry. [ABSTRACT FROM AUTHOR]

Justice‐involved adolescents (JIA) are at higher risk for opioid misuse (OM) and opioid‐related overdose than nonoffending adolescents. Untreated OM can lead to severe consequences (e.g., trauma), which may be harsher for female JIA. Therefore, examining risk and protective factors, such as parental supervision, is essential to identify factors that may impact OM. The current study used a statewide, cross‐sectional dataset including 79,960 JIA from the Florida Department of Juvenile Justice. Stratified logistic regression analyses were conducted. Results indicated that JIA who experienced sporadic or inadequate supervision had 2.14 and 3.54 higher odds, respectively, of misusing opioids compared to JIA who experienced consistent supervision. Female JIA who experienced sporadic or inadequate supervision had 2.23 and 3.70 higher odds, respectively, of misusing opioids. Results suggest parental supervision is an important protective factor that should be considered in developing prevention and treatment efforts that serve JIA who misuse opioids, especially females. [ABSTRACT FROM AUTHOR]

Opioid use disorder is a chronic relapsing disorder. The brain adapts to opioids that are taken for pain treatment or recreational use so that abstinence becomes a true challenge for individuals with opioid use disorder. Studying brain dysfunction at this stage is difficult, and human neuroimaging has provided highly heterogeneous information. Here, we took advantage of an established mouse model of morphine abstinence together with functional magnetic resonance imaging to investigate whole-brain functional connectivity (FC) first at rest and then in response to an acute morphine challenge during image acquisition. Hierarchical clustering of seed pair correlation coefficients showed modified FC in abstinent animals, brainwide and regardless of the condition. Seed-to-voxel analysis and random forest classification, performed on data at rest, indicated that the retrosplenial cortex (a core component of the default mode network) and the amygdala (a major aversion center) are the best markers of abstinence, thus validating the translatability of the study. Seed pair network clustering confirmed disruption of a retrosplenial cortex–centered network, reflecting major reorganization of brain FC. The latter analysis also identified a persistent but unreported morphine signature in abstinent mice at rest, which involves cortical and midbrain components and characterizes the enduring morphine footprint. Finally, dynamic FC analysis revealed that the intrascanner acute morphine challenge modified FC faster and more broadly in abstinent animals, demonstrating brainwide adaptations of FC reactivity to an acute opioid challenge. This study used a unique experimental design to demonstrate that a prior history of chronic opioid exposure leaves a durable pharmacological signature on brain communication, with implications for pain management and recovery from opioid use disorder. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis examines evidence from 39 studies on hypersensitivity to cold pain among patients with opioid use disorder and its association with indices of opioid tolerance, withdrawal, and abstinence. Key Points: Question: Is hyperalgesia in patients with opioid use disorder associated with opioid use? Findings: This systematic review and meta-analysis of 39 studies and more than 1300 individuals with and 700 individuals without a history of opioid use disorder found hypersensitivity to cold pain in patients undergoing opioid agonist treatment for opioid use disorder. Evidence for a relationship between this hyperalgesia and indices of opioid tolerance, withdrawal, and abstinence was inconclusive. Meaning: It remains unclear based on the current literature whether the observed hyperalgesia in patients with opioid use disorder is associated with opioid use or with other, non–opioid-related factors. Importance: Short-term and long-term opioid treatment have been associated with increased pain sensitivity (ie, opioid-induced hyperalgesia). Treatment of opioid use disorder (OUD) mainly involves maintenance with methadone and buprenorphine, and observations of heightened cold pain sensitivity among patients are often considered evidence of opioid-induced hyperalgesia. Objective: To critically examine the evidence that hyperalgesia in patients with OUD is related to opioid use. Data Sources: Web of Science, PubMed, and Embase between March 1, 2023, and April 12, 2024, were searched. Study Selection: Studies assessing cold pressor test (CPT) pain responses during treatment seeking, pharmacological treatment, or abstinence in patients with OUD history were included. Data Extraction and Synthesis: Multilevel random-effects models with robust variance estimation were used for all analyses. Study quality was rated with the JBI checklist. Funnel plots and Egger regression tests were used to assess reporting bias. Main Outcomes and Measures: Main outcomes were pain threshold, tolerance, and intensity in patients and healthy controls, and unstandardized, standardized (Hedges g), and percentage differences (%Δ) in these measures between patients and controls. The association between pain sensitivity and opioid tolerance, withdrawal, and abstinence indices was tested with meta-regression. Results: Thirty-nine studies (1385 patients, 741 controls) met the inclusion criteria. Most studies reported CPT data on patients undergoing opioid agonist treatment. These patients had a mean 2- to 3-seconds lower pain threshold (95% CI, −4 to −1; t test P =.01; %Δ, −22%; g = −0.5) and 29-seconds lower pain tolerance (95% CI, −39 to −18; t test P <.001; %Δ, −52%; g = −0.9) than controls. Egger tests suggested that these differences may be overestimated. There were some concerns of bias due to inadequate sample matching and participant dropout. Meta-regressions yielded no clear support for hyperalgesia being opioid related. Conclusion and Relevance: Patients receiving opioid agonist treatment for OUD are hypersensitive to cold pain. It remains unclear whether hyperalgesia develops prior to, independent of, or as a result of long-term opioid treatment. Regardless, future studies should investigate the impact of hyperalgesia on patients' well-being and treatment outcomes. [ABSTRACT FROM AUTHOR]

• This case series describes PRS-delivered behavioral activation to support MT. • Three cases were chosen to depict intervention adaption for varying presentations. • The PRS worked with each participant to implement value-driven, rewarding activities. • PRS shared experiences and intervention flexibility played key roles in pilot success. While methadone treatment (MT) is effective in treating opioid use disorder (OUD), retention remains an issue nationwide, especially among low-income, minoritized populations. Peer recovery specialists (PRSs), individuals with lived substance use experience, are particularly well suited to support vulnerable populations, though often are not trained in delivering evidence-based interventions. Thus, our team developed a Type 1 hybrid effectiveness-implementation open-label pilot trial to evaluate the effectiveness of PRS-delivered BA (Peer Activate) in improving MT retention and establish feasibility, acceptability and PRS fidelity of the intervention. In this case series, we provide a more in-depth depiction of the adaption of Peer Activate and present three cases to illustrate how Peer Activate can be implemented among patients in routine MT care and adapted to meet the needs of varying clinical presentations. We include descriptive data on participant substance use and MT outcomes to supplement the narrative discussion. While varying participant presentations and needs presented challenges to the PRS interventionist, the PRS utilized his shared, lived substance use and recovery experiences and met participants where they were at, as well as successfully used BA techniques, ultimately leading to intervention success. [ABSTRACT FROM AUTHOR]

Introduction: Illicit drug use, particularly the synthetic opioid fentanyl, presents a significant global health challenge. Previous studies have shown that fentanyl enhances viral replication; yet, the mechanisms by which it affects HIV pathogenesis remain unclear. This study investigated the impact of fentanyl on HIV replication in CD4+ T lymphocytes. Methods: CD4+ T lymphocytes from HIV-negative donors were activated, infected with HIVNL4-3, and treated with fentanyl. HIV proviral DNA and p24 antigen expression were quantified using real-time PCR and ELISA, respectively. Single-cell RNA libraries were analyzed to identify differentially expressed genes. Results: Results indicated that fentanyl treatment increased HIV p24 expression and proviral DNA levels, and naltrexone mitigated these effects. Single-cell RNAseq analysis identified significantly altered gene expression in CD4+ T lymphocytes. Discussion: The results of our findings suggest that fentanyl promotes HIV replication ex vivo, emphasizing the need for a deeper understanding of opioidvirus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder. [ABSTRACT FROM AUTHOR]

Objective: This qualitative study aimed to examine how states implemented COVID-19 public health emergency–related federal policy flexibilities for opioid use disorder treatment from the perspective of state-level behavioral health policy makers. Recommendations are given for applying lessons learned to improve the long-term impact of these flexibilities on opioid use disorder treatment. Methods: Eleven semistructured interviews were conducted with 13 stakeholders from six state governments, and transcripts were qualitatively coded. Data were analyzed by grouping findings according to state-, institution-, and provider-level barriers and facilitators and were then compared to identify overarching themes. Results: Policy makers expressed positive opinions about the opioid use disorder treatment flexibilities and described benefits regarding treatment access, continuity of care, and quality of care. No interviewees reported evidence of increased adverse events associated with the relaxed medication protocols. Challenges to state-level implementation included gaps in the federal flexibilities, competing state policies, facility and provider liability concerns, and persistent systemic stigma. Conclusions: As the federal government considers permanent adoption of COVID-19–related flexibilities regarding opioid use disorder treatment policies, the lessons learned from this study are crucial to consider in order to avoid continuing challenges with policy implementation and to effectively remove opioid use disorder treatment barriers. [ABSTRACT FROM AUTHOR]

Background: The treatment of opioid addiction mainly involves the medical administration of methadone or other opioids, aimed at gradually reducing dependence and, consequently, the need for illicit opioid procurement. Thus, initiating opioid maintenance therapy with a lower level of dependence would be advantageous. There is compelling evidence indicating that opioids induce brain oxidative stress and associated glial activation, resulting in the dysregulation of glutamatergic homeostasis, which perpetuates drug intake. The present study aimed to determine whether inhibiting oxidative stress and/or neuroinflammation reduces morphine self-administration in an animal model of opioid dependence. Methods: Morphine dependence, assessed as voluntary morphine self-administration, was evaluated in Wistar-derived UChB rats. Following an extended period of morphine self-administration, animals were administered either the antioxidant N-acetylcysteine (NAC; 40 mg/kg/day), the anti-inflammatory ibudilast (7.5 mg/kg/day) or the combination of both agents. Oxidative stress and neuroinflammation were evaluated in the hippocampus, a region involved in drug recall that feeds into the nucleus accumbens, where the levels of the glutamate transporters GLT-1 and xCT were further assessed. Results: Daily administration of either NAC or ibudilast led to a mild reduction in voluntary morphine intake, while the co-administration of both therapeutic agents resulted in a marked inhibition (-57%) of morphine self-administration. The administration of NAC or ibudilast markedly reduced both the oxidative stress induced by chronic morphine intake and the activation of microglia and astrocytes in the hippocampus. However, only the combined administration of NAC + ibudilast was able to restore the normal levels of the glutamate transporter GLT-1 in the nucleus accumbens. Conclusion: Separate or joint administration of an antioxidant and anti-inflammatory agent reduced voluntary opioid intake, which could have translational value for the treatment of opioid use disorders, particularly in settings where the continued maintenance of oral opioids is a therapeutic option. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectiveMethodsResultsConclusionsFew studies to date have examined the number of comorbid substances used alongside Prescription Opioid Misuse (POM) to predict suicidal behaviors among US young adults.This study investigated the relationship between comorbid substance use with POM and suicidal behaviors among the US young adults.Data were from individuals aged 18–25 (N = 69,204, 51.8% female) in the 2015–2019 National Surveys on Drug Use and Health (NSDUH). The final analytic sample for logistic regression was 36,892 young adults.After controlling for key covariates, the combination of POM and three or more illicit drugs were at the greatest odds of suicidal ideation (OR = 2.57, 95% CI = 1.61 − 4.11, p < 0.001) and attempts (OR = 3.57, 95% CI = 1.89 − 6.76, p < 0.001) compared to those without POM or drug use.The study provides evidence of a dose-response relationship between the number of illicit drugs uses alongside POM and the suicide risk as a clinically important phenomenon with implication for intervention. Findings highlight that POM, with or without illicit drug use, can serve as a behavioral and clinical indicator for identifying young adults at heightened risk of suicidality. This group warrants prioritized intervention targets to ensure timely access to developmentally appropriate clinical treatment, aiming to mitigate addiction progression and prevent harm and mortality. [ABSTRACT FROM AUTHOR]

The opioid epidemic continues to have a staggering impact on millions of individuals and families across all socioeconomic levels and communities. Recent studies suggest high numbers of patients presenting for surgery with reported opioid misuse and/or opioid use disorder (OUD). Anesthesiologists often lack basic education to treat patients suffering with OUD or patients in recovery from this treatable disease. This manuscript will provide a review of the American Society of Anesthesiology and Pain Medicine Multisociety Working Group Practice Advisory recommendations on existing OUD treatment barriers and perioperative management best practices; it will also demonstrate the benefits that greater involvement of the anesthesiologist can have in managing patients with OUD perioperatively. [ABSTRACT FROM AUTHOR]

Credibility and expectancy are important aspects of therapy/treatment processes. We aimed to perform cross-cultural validation and examine the psychometric properties of the Credibility/Expectancy Questionnaire (CEQ). Ninety-one patients with opioid use disorder from Tobacco, Alcohol, and Drug Addiction Treatment Program were included in the study. Sociodemographic data form, CEQ, Beck Depression Inventory (BDI), State and Trait Anxiety Inventory (STAI), and Attitudes Toward Seeking Psychological Professional Help Scale-Short Form (ATSPPHS-SF) were filled out by participants. Confirmatory factor analyses showed that CEQ has two factors in our sample, similar to the original version. Reliability analyses showed that CEQ has a high internal consistency and test-retest reliability. Regarding convergent validity results, CEQ was correlated with ATSPPHS-SF. No significant correlation was found between CEQ and BDI and STAI regarding discriminant validity results. In conclusion, the Turkish version of CEQ is a valid, reliable scale and could be used in patients with opioid use disorder. In patients with opioid use disorder, we contributed to the addiction literature by adapting a short and effective survey that measures trust and expectation. [ABSTRACT FROM AUTHOR]

Purpose: Despite their dangerous side effects, opioid drugs remain a standard of care for moderate to severe pain with few alternatives. Strategies to maintain the analgesic effects of opioids while minimizing the associated risks are needed. Pre-clinical studies have shown using a dopamine 3 receptor (D3R) agonist as an adjuvant to morphine provides superior analgesia against painful stimuli compared to morphine alone. Our objective was to test if adjunct treatment with a D3R agonist can lead to a reduction in opioid use while maintaining effective analgesia. Patients and methods: This study was set up as a double-blinded, placebocontrolled randomized trial. Enrollment included acute renal colic patients presenting to the emergency department, from which patients were randomized to either the "control" or "study arm". The control group received standard treatment of care (morphine, 0.1 mg/kg; i.v.) and an oral placebo pill. The experimental group received half-dosed morphine and oral pramipexole pill (0.25 mg). Pain measurements including a numerical pain scale and visual analog scale were collected from enrollees at baseline and every subsequent 15 min. Results: A total of 19 patients completed the study, 10 in the experimental arm and 9 in the control arm. During the study period, effective analgesia (50% decrease from baseline) was achieved in 80% of patients in the experimental arm vs. 33.3% in the control arm. Conclusion: Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain and potentially other acute pain conditions. [ABSTRACT FROM AUTHOR]

AbstractThe increasing incidence of opioid use disorder (OUD) among pregnant women in the United States constitutes a significant public health concern, jeopardizing both maternal and fetal health. Proposed solutions include opioid maintenance therapy, telemedicine, and integrated prenatal care centers. These strategies seek to mitigate harm and enhance therapeutic accessibility, yet encounter obstacles, including stigma, technological access, and ethical problems. While opioid maintenance therapy stabilizes addiction, telemedicine expands access, and integrated centers streamline care, each strategy requires policy support, community acceptance, and further evaluation to optimize outcomes for pregnant women with OUD. [ABSTRACT FROM AUTHOR]

Background: Opioid-related overdoses significantly contribute to mortality in pregnancy and the postpartum period. Few studies report risk factors predisposing pregnant and postpartum patients with opioid use disorder (OUD) to overdose.Objective: This scoping review aims to describe the risk factors predisposing pregnant and postpartum patients with OUD to overdose.Method: Included studies identified pregnant and/or postpartum patients with OUD and differentiated between those who experienced overdose and those who did not. Of the 1060 articles, 8 met the criteria, examining 90,860 pregnant and postpartum patients with OUD.Results: Consistent use of medications for OUD (MOUD) during pregnancy and the postpartum period was the most frequently identified factor reducing overdose risk. Critical times of heightened overdose risk include the first trimester and the 7–12-month postpartum period. Pregnancy complications, such as stillbirth, severe maternal morbidity, preterm birth, and cesarean delivery, also increase risk. Opioid overdose is associated with being houseless, incarcerated, young, unmarried, publicly insured, not graduating high school, co-occurring substance use disorders, and inadequate prenatal care. Legislative changes, such as not classifying OUD in pregnancy as “child abuse” and increasing Medicaid reimbursement for Screening, Brief Intervention, and Referral to Treatment programs, are crucial to reducing risk. The impact of race and the influence of co-occurring psychiatric disorders was inconsistently reported.Conclusion: This scoping review identifies significant risk factors for opioid overdose in pregnant and postpartum patients. Improving access through enhanced Medicaid reimbursement, non-punitive reporting policies, and non-stigmatized care are keys to reducing overdose. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsOpioid-related stigma can affect the health and recovery of individuals with opioid use disorder (OUD). As such, campaigns to reduce stigma are needed. We evaluated Life Unites Us (LUU), a comprehensive social media campaign to reduce public stigma of opioids and those who use them, 12 months after campaign launch.A cross-sectional web survey of 1,045 people was used to assess differences in public stigma by exposure to LUU. Survey items focused on public OUD stigma and were divided into three subscales: desire for social distance, treatment availability and effectiveness, and general attitudes.Controlling for relevant covariates (i.e. gender, political ideology, education level, race), individuals exposed to LUU endorsed less stigma in the desire for social distance and treatment subscales. There were no significant differences in stigma for the general attitudes subscale. Those who identified as more politically conservative held more stigma across all subscales than those who identified as less politically conservative. Females reported less treatment and general OUD stigma than males.Findings suggest that comprehensive social media campaigns that foster connections, educate the public, and advocate for community-level change may positively influence public attitudes toward individuals with OUD and create a more supportive environment for recovery. [ABSTRACT FROM AUTHOR]

Introduction: There is increased clinical use of gabapentin, these trends appear to chronologically align with the opioid overdose crisis and particularly with the increased restrictions on opioid prescription. Objectives: The study aimed to assess the clinical variables, pain quality, and severity among patients with opioid use disorder as the main substance with and without gabapentin comorbid use. Methods: The research involved 60 patients diagnosed with substance use disorder, divided into two groups: opioid use as the main substance and opioid use with comorbid gabapentin. All participants were assessed using a semi-structured clinical addiction interview, the structured clinical interview for diagnostic and statistical manual of mental disorders, the Addiction Severity Index, urine drug test, McGill Pain Questionnaire, and Douleur Neuropathique en 4 Questionnaire, in one interview setting. Results: The study showed that pain relief was the main desirable effect in the gabapentin group, with 66.2% of the group experiencing it. Euphoria was the desirable effect in the opioid group, while overdose was more common in the gabapentin group. Respiratory complications were also more common in the Gabapentin group. Conclusion: The study concluded that patients with comorbid gabapentin use disorder had a higher frequency of overdose, history of pain, and significant neuropathic pain, while less abstinence. [ABSTRACT FROM AUTHOR]

Aims Design Setting Participants Measurements Findings Conclusions To understand how the US public defines recovery from opioid misuse and the recovery‐related resources it views as most helpful, and to compare differences by opioid misuse history and demographic characteristics.Observational study of data from the nationally representative AmeriSpeak® Panel survey administered in October/November 2021.United States.6515 adults (≥ 18 years).Respondents ranked 10 definitions of recovery (religious in nature; spiritual in nature; physical/mental in nature; contributing to society; enhanced quality of life; seeking professional help; having a sense of purpose; moderate/controlled substance use; no drug use; abstaining from all substance use) and 9 resources that might contribute to recovery (primary care physician; intensive inpatient program; residential rehabilitation program; self‐help group; therapist/psychologist/social worker; prescribed medication; talking to family/friends; spiritual/natural healer; faith‐based organization). We explored differences in rankings by opioid misuse history (personal vs. family/friend vs. no history) and demographic characteristics (race, sex, age) using multivariable ordinal logistic regression.Seeking professional help was the most endorsed recovery definition overall [mean (M) = 6.97, standard error (SE) = 0.03]. Those with personal opioid misuse history ranked enhanced quality of life (B = 0.16, P = 0.049) and having a sense of purpose (B = 0.16, P = 0.029) significantly higher, and ranked abstaining from substance use (B = ‐0.20, P = 0.009) significantly lower as recovery definitions than those without a history of opioid misuse. Compared with White respondents, Black (B = 0.60, P < 0.001) and Hispanic (B = 0.55, P < 0.001) respondents defined recovery as more religious in nature. Residential rehabilitation program was identified as the most helpful resource for recovery (M = 7.16, SE = 0.02), while prescribed medication received a relatively low ranking overall (M = 4.05, SE = 0.03). Those with family/friend opioid misuse history ranked prescribed medication as less helpful than others (B = ‐0.14, P = 0.003).The general US public's views around recovery from opioid misuse appear to focus on abstinence and formal treatment receipt, while people with a history of opioid misuse place less emphasis on abstinence and greater emphasis on other aspects of well‐being. [ABSTRACT FROM AUTHOR]

Introduction: Effective adjunctive therapeutic treatments for patients with opioid use disorder (OUD) on medication for OUD (MOUD) in primary care settings are needed to address high rates of mental illness and stress. Behavioral activation (BA) is a brief, evidence-based therapy that has potential to improve quality of life in people with OUD. The purpose of this pilot study was to evaluate the feasibility and acceptability of values-based BA (VBA) as an adjunct treatment for patients receiving MOUD in primary care. Methods: Participants were recruited for a single-arm pilot trial of BA in a primary care setting. VBA was adapted for people with OUD and included 4-6 sessions delivered over 12 weeks with a behavioral health consultant, either inperson or virtually. Feasibility was assessed as recruitment percent and pace and retention percent. Acceptability was assessed with the Client Satisfaction Questionnaire-8 (CSQ-8). Participants completed self-report measures of well-being, depression, substance use, and psychological processes of change at baseline, mid-intervention (6-weeks), and post-intervention (12-weeks). Participants engaged in a brief interview about their experiences at the end of the intervention. Results: Twenty-one participants enrolled in the intervention (66.7% female, M age = 44.0 years, 19% of those invited). Participants completed an average of 5.1 BA sessions (SD = 1.6) and most (90%) were retained through 12 weeks. Participants rated the intervention as highly acceptable on the CSQ-8 (M = 30.4/32.0, SD = 1.6). In qualitative interviews, participants reported that working with the therapist and setting values-based goals were helpful, while also recommending more tailoring to patients' needs and offering the program early in MOUD treatment. Preliminary efficacy data suggest the program was associated with small to moderate improvements in life satisfaction (Cohen's d = 0.25) and positive affect (d = 0.62), whereas there were no changes in depression (d = 0.09) or negative affect (d = -0.07) in a group with low depression at baseline. Discussion: VBA adapted for patients on MOUD in primary care was feasible to deliver and acceptable to participants. Minor modifications to the target population and treatment manual could increase the program's impact. Future studies will test the efficacy of the intervention in improving quality of life and OUD treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Understanding the heterogeneity of opioid overdose fatalities is critical to developing effective preventive interventions. This study examines patterns of care contacts among people who subsequently died from opioid overdose. The aim was to identify distinct groups of deceased individuals, based on their contacts with different care agencies in their last year of life. Methods: A retrospective registry study was conducted in Skåne, Southern Sweden. All recorded opioid overdose fatalities during the study period were included, n = 191. Latent class analysis was used to identify patterns of care contacts in the last year of life. Results: Three distinct classes were identified: "Few care contacts," with limited interaction with any services; "Social service contacts," comprising individuals who predominantly had contacts with the social services and, to a lesser extent, with prison and probation services; and "Numerous care contacts," with extensive contacts with both healthcare and social services. The "few care contacts" class comprises about half of the population. This is an important finding, since this group has not been clearly visible in previous research. The analysis indicates significant gaps in service provision, particularly regarding substance use treatment and mental health support. Conclusions: Using a person-centred approach, this article offers a novel way of analysing care contacts among people who subsequently died from opioid overdose. The identification of distinct groups, particularly a large group of people with minimal contact with the community care system, highlights the need for more targeted outreach and support work. Developing targeted interventions in emergency and inpatient care settings may provide an opportunity to reach the group with few care contacts. [ABSTRACT FROM AUTHOR]

Background: A staff e-learning course was developed to prepare for scaling up a national take-home naloxone (THN) program in Norway. The aims of the study were to (a) describe participant characteristics for those that completed a THN e-learning course, (b) compare opioid overdose knowledge scores before and after e-learning course completion, and (c) to explore subsequent THN distribution by those trained. Methods: This was a quasi-experimental pre-test, post-test longitudinal cohort study of individuals completing a THN e-learning course from April 2021 to May 2022. Frequency analyses were performed for participant characteristics and subsequent naloxone distributions at 1-week and 1-month follow-up. The opioid overdose knowledge scale (OOKS) was used to measure pre-test-posttest knowledge among participants. Wilcoxon signed-rank test was performed for comparison between pre-test and post-test. Effect size was calculated using Cohen criteria. Results: In total, 371 individuals were included in this study. Most were either nurses or social workers (n = 277, 75%). Participant knowledge increased by medium or large effect for all items measured. At 1-month follow-up, 15% reported naloxone distribution. During the study period, 94 naloxone kits were distributed. Major reasons for not distributing were "clients not interested", "workplace not distributing" and "workplace in process of distributing". Conclusions: Our findings suggest that an e-learning course is equally effective in terms of knowledge transfer as an in-person classroom setting, and may provide engagement in terms of naloxone distribution. However, our findings also emphasize the importance of clear implementation routines, including support from central coordinators to optimize the implementation process. [ABSTRACT FROM AUTHOR]

Opioid misuse, addiction, and associated overdose deaths remain global public health crises. Despite the tremendous need for pharmacological treatments, current options are limited in number, use, and effectiveness. Fundamental leaps forward in our understanding of the biology driving opioid addiction are needed to guide development of more effective medication-assisted therapies. This Review focuses on the omics-identified biological features associated with opioid addiction. Recent GWAS have begun to identify robust genetic associations, including variants in OPRM1, FURIN, and the gene cluster SCAI/PPP6C/RABEPK. An increasing number of omics studies of postmortem human brain tissue examining biological features (e.g., histone modification and gene expression) across different brain regions have identified broad gene dysregulation associated with overdose death among opioid misusers. Drawn together by meta-analysis and multi-omic systems biology, and informed by model organism studies, key biological pathways enriched for opioid addiction-associated genes are emerging, which include specific receptors (e.g., GABAB receptors, GPCR, and Trk) linked to signaling pathways (e.g., Trk, ERK/MAPK, orexin) that are associated with synaptic plasticity and neuronal signaling. Studies leveraging the agnostic discovery power of omics and placing it within the context of functional neurobiology will propel us toward much-needed, field-changing breakthroughs, including identification of actionable targets for drug development to treat this devastating brain disease. [ABSTRACT FROM AUTHOR]

Aims Design Setting Participants Measurements Findings Conclusions This study aimed to estimate the strength of association between prescriptions of glucose‐dependent insulinotropic polypeptide (GIP) and/or glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) and the incidence of opioid overdose and alcohol intoxication in patients with opioid use disorder (OUD) and alcohol use disorder (AUD), respectively. This study also aimed to compare the strength of the GIP/GLP‐1 RA and substance use‐outcome association among patients with comorbid type 2 diabetes and obesity.A retrospective cohort study analyzing de‐identified electronic health record data from the Oracle Cerner Real‐World Data.About 136 United States of America health systems, covering over 100 million patients, spanning January 2014 to September 2022.The study included 503 747 patients with a history of OUD and 817 309 patients with a history of AUD, aged 18 years or older.The exposure indicated the presence (one or more) or absence of GIP/GLP‐1 RA prescriptions. The outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort. Potential confounders included comorbidities and demographic factors.Patients with GIP/GLP‐1 RA prescriptions demonstrated statistically significantly lower rates of opioid overdose [adjusted incidence rate ratio (aIRR) in OUD patients: 0.60; 95% confidence interval (CI) = 0.43–0.83] and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI = 0.40–0.63) compared to those without such prescriptions. When stratified by comorbid conditions, the rate of incident opioid overdose and alcohol intoxication remained similarly protective for those prescribed GIP/GLP‐1 RA among patients with OUD and AUD.Prescriptions of glucose‐dependent insulinotropic polypeptide and/or glucagon‐like peptide‐1 receptor agonists appear to be associated with lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder and alcohol use disorder. The protective effects are consistent across various subgroups, including patients with comorbid type 2 diabetes and obesity. [ABSTRACT FROM AUTHOR]

Despite growing concern about opioid misuse and mental health of college students, little is known about this population who are at high risk of co-occurrence and unmet needs. This national study aims to estimate the prevalence of opioid misuse, examine correlates with anxiety and depression symptoms, and quantify help-seeking behaviors among U.S. college students. Data come from students in the Healthy Minds Study between 2017 and 2020 (n = 176,191). Validated screening tools assessed mental health symptoms (PHQ-9, GAD-7). Marginal effects of logistic regression models estimate the effect of opioid misuse on mental health symptoms, help-seeking and academic performance. 782 students indicated past month opioid misuse. Student opioid misuse was associated with 24.1 percentage point increase in the probability of screening positive for anxiety/depression (p < 0.001) and 3.6 percentage point increase in the probability of informal help-seeking (p = 0.017). Less than half of students with opioid misuse and a positive depression/anxiety screen received any treatment in the past year. Limitations to this study include: possible non-response bias, as it is unknown whether students with opioid misuse may be differentially-likely to respond to the survey; differing time frame for opioid misuse and mental health questions; and data was collected prior to the COVID-19 pandemic. This large, multi-campus study underlines the need for more partnership between substance use and mental health services on campus. It also highlights that college peers could receive training in ways to best help students who misuse opioids, directing them to on- or off-campus care. • 782 students (0.44 %) indicated past month opioid misuse. • Opioid misuse associated with 24.1 percentage point increase in anxiety/depression. • Opioid misuse associated with 3.6 percentage point increase of informal help-seeking. • <50 % with opioid misuse and anxiety/depression received past-year treatment. [ABSTRACT FROM AUTHOR]

Exposure to traumatic events is a frequent source of distress, provoking isolated symptoms such as distressing memories (DM) to full-blown post-traumatic stress disorder (PTSD). We aimed to assess the continuum theory using DM as an isolated symptom, and to examine trauma consequences in a exposed to traumatic events. Using data from the National Epidemiologic Study of Alcohol and Related Conditions III, we assessed the prevalence of DM in a trauma exposed sample, and examined their sociodemographic and lifetime psychiatric correlates, comparing three groups: (i) controls (no DM, no PTSD); (ii) participants with isolated DM without PTSD; (iii) participants with PTSD. We estimated the sensitivity and specificity of DM for PTSD diagnosis. In our sample of 17,505 participants exposed to trauma, 13 % had PTSD and 42 % had DM without PTSD. The sensitivity of DM for the diagnosis of PTSD was 95.14 %, specificity was 51.91 %. Participants with DM and those with PTSD shared the same socio-demographic correlates. Participants with DM reported more lifetime psychiatric disorders (mood disorders - mainly depressive disorders and bipolar type 1 disorder; anxiety disorders - mainly social anxiety disorder, substance use disorders - mainly opioid use disorder and cannabis disorder; eating disorders - mainly binge eating disorder; personality disorders - mainly borderline personality disorder- and suicidality) than controls, but less than participants with PTSD. DM represent an intermediate state between well-being and post-traumatic stress disorder; DM is also associated with other psychiatric disorders. It should be considered as a transdiagnostic psychiatric symptom useful for clinicians in identifying psychiatric vulnerability. • In our sample of 17,505 trauma exposed participants, 13 % had PTSD and 42 % had distressing memories without PTSD. • Distressing memories represent an intermediate state between well-being and post-traumatic stress disorder. • Distressing memories are transdiagnostic psychiatric symptoms useful in identifying psychiatric vulnerability. [ABSTRACT FROM AUTHOR]

Background and Aims Design Setting Participants Measurements Findings Conclusions Opioid use disorder (OUD) is treatable with buprenorphine/naloxone (buprenorphine), but many patients discontinue treatment prematurely. The aim of this study was to assess the influence of patient‐ and prescriber‐level characteristics relative to several patient outcomes following the initiation of buprenorphine treatment for OUD.This was a retrospective observational investigation. We used the Public Health Data Warehouse from the Massachusetts Department of Public Health to construct a sample of patients who initiated buprenorphine treatment between 2015 and 2019. We attributed each patient to a prescriber based on information from prescription claims. We used multilevel models to assess the influence of patient‐ and prescriber‐level characteristics on each outcome.Massachusetts, USA.The study cohort comprised 37 955 unique patients and 2146 prescribers. Among patients, 64.6% were male, 52.6% were under the age of 35 and 82.2% were White, non‐Hispanic. For insurance coverage, 72.1% had Medicaid.The outcome measures were poor medication continuity, treatment discontinuation and opioid overdose, all assessed within a 12‐month follow‐up period that began with a focal prescription for buprenorphine. Each patient had a single follow‐up period. Poor medication continuity was defined as medication gaps totaling more than 7 days during the initial 180 days of buprenorphine treatment and treatment discontinuation was defined as having a medication gap for 2 consecutive months within the 12‐month follow‐up period.The patient‐level rates for poor medication continuity, treatment discontinuation and opioid overdose were 59.7% [95% confidence interval (CI) = 59.2–60.2], 57.4% (95% CI = 56.9–57.9) and 10.3% (95% CI = 10.0–10.6), respectively, with 1.1% (95% CI = 1.0–1.2) experiencing a fatal opioid overdose. At the patient level, after adjustment for covariates, adverse outcomes were associated with race/ethnicity as both Black, non‐Hispanic and Hispanic patients had worse outcomes than did White, non‐Hispanic patients (Black, non‐Hispanic ‐‐ poor continuity: 1.50, 95% CI = 1.34–1.68; discontinuation: 1.44, 95% CI = 1.30–1.60; Hispanic ‐‐ poor continuity: 1.21, 95% CI = 1.12–1.31; discontinuation: 1.38, 95% CI = 1.28–1.48). Patients with insurance coverage through Medicaid also had worse outcomes than those with commercial insurance (poor continuity: 1.18, 95% CI = 1.11–1.26; discontinuation: 1.09, 95% CI = 1.03–1.16; overdose: 1.98, 95% CI = 1.75–2.23). Pre‐treatment mental health conditions and other types of chronic illness were also associated with worse outcomes (History of mental health conditions ‐‐ poor continuity: 1.11, 95% CI = 1.06–1.17; discontinuation: 1.05, CI = 1.01–1.10; overdose: 1.47, 95% CI = 1.36–1.60; Chronic health conditions ‐‐ poor continuity: 1.15, 95% CI = 1.05–1.27; discontinuation: 1.15, 95% CI = 1.05–1.26; overdose: 1.83, 95% CI = 1.60–2.10; History of substance use disorder other than for opioids ‐‐ poor continuity: 1.54, 95% CI = 1.46–1.62; discontinuation: 1.54, 95% CI = 1.47–1.62; overdose: 1.93, 95% CI = 1.80–2.07). At the prescriber level, after adjustments for covariates, adverse outcomes were associated with clinical training, as primary care physicians had higher rates of adverse outcomes than psychiatrists (poor continuity: 1.12, 95% CI = 1.02–1.23; discontinuation: 1.04, 95% CI = 1.01–1.09). A larger prescriber panel size, based on number of patients being prescribed buprenorphine, was also associated with higher rates of adverse outcomes (poor continuity: 1.36, 95% CI = 1.27–1.46; discontinuation: 1.21, 95% CI = 1.14–1.28; overdose: 1.10, 95% CI = 1.01–1.19). Between 9% and 15% of the variation among patients for the outcomes was accounted for at the prescriber level.Patient‐ and prescriber‐level characteristics appear to be associated with patient outcomes following buprenorphine treatment for opioid use disorder. In particular, patients' race/ethnicity and insurance coverage appear to be associated with substantial disparities in outcomes, and prescriber characteristics appear to be most closely associated with medication continuity during early treatment. [ABSTRACT FROM AUTHOR]

Background: In the context of the opioid overdose crisis, understanding the barriers to seeking, attaining and remaining in treatment for patients with opioid use disorder (OUD) is a public health issue. To date, very few studies have assessed the "self-stigma" (i.e., the internalization of negative societal attitudes and stereotypes about oneself, leading to self-judgment) and "perceived stigma" (i.e., the belief that others hold negative attitudes towards oneself due to a particular condition) experienced by patients with OUD receiving opioid agonist treatment (OAT), and none have done so in France. Our study aimed to quantify self-stigma, explore some aspects of perceived stigma, determine the factors associated with greater self-stigma and examine whether the level of self-stigma was related to a delay in seeking care. Methods: The STIGMA study was a monocentric, cross-sectional study. The data were collected in a French hospital addiction medicine department. Participants were outpatients with current or past OUD who were still receiving or had received OAT. A questionnaire assessing sociodemographics; OUD characteristics; perceived stigma; and quantification of self-stigma by the Self-Stigma Scale-Short, was administered. Results: A total of 73 questionnaires were included in the analysis. Nearly two-thirds of the patients had a "moderate to high" level of self-stigma. These patients were significantly younger at OUD onset and were significantly more likely to have at least one dependent child than patients reporting a "very low to low" level of self-stigma. Nearly half of the participants experienced perceived stigma from a healthcare professional regarding their OUD or OAT, and nearly one-third of the participants were refused care from a healthcare professional because of their OUD or OAT. Moreover, a quarter of the sample reported delaying care due to fear of being stigmatized. We did not find a relationship between self-stigma levels and a delay in seeking care. Conclusions: Our study highlights the need to detect stigma and to improve training in addiction medicine. [ABSTRACT FROM AUTHOR]

Background: Overdose is a leading cause of maternal mortality; in response, maternal mortality review committees have recommended expanding substance use disorder (SUD) screening, improving collaboration between obstetric and SUD treatment providers, and reducing fragmentation in systems of care. We undertook an analysis of the perinatal SUD treatment landscape in Baltimore, Maryland in order to identify barriers to treatment engagement during pregnancy and the postpartum period and guide system improvement efforts. Methods: We conducted a survey of seven birthing hospitals, 31 prenatal care practices, and 108 SUD treatment providers in Baltimore from April-June 2023. Organizations were asked to quantify care for perinatal patients with opioid use disorder (OUD) as well as about screening, service availability, referral practices, and support needed to improve care. Results: 61% of the 145 contacted organizations responded. Birthing hospitals reported caring for pregnant persons with OUD with greater frequency than prenatal care practices or SUD treatment programs. Most birthing hospitals and prenatal care practices reported screening for OUD at intake, but the minority reported using validated tools. Service availability varied by type of organization and type of service. In general, prenatal care practices offered the fewest number of SUD-related services. Most SUD treatment programs that offered buprenorphine or methadone to the general population also offered these medications to pregnant patients. Withdrawal management for comorbid alcohol/benzodiazepine use disorders during pregnancy was more limited. The majority of birthing hospitals and prenatal care practices reported offering neither direct naloxone distribution nor prescriptions. Few SUD treatment programs offered tailored services for perinatal patients or for parents of young children, and many programs do not permit children onsite. Respondents reported high levels of interest in education and consultative support on SUD treatment in pregnancy within obstetric settings and on pregnancy-related medical concerns within SUD programs. Conclusions: This project provides a comprehensive picture of services available for treatment of perinatal OUD in a major US city. Results have served as a guide for ongoing citywide system improvement efforts by our project team and offer a model for other jurisdictions hoping to strengthen services for perinatal OUD and reduce maternal mortality. [ABSTRACT FROM AUTHOR]

Opioid use disorders (OUD) are a major issue in the U.S. Current treatments for pregnant women, like methadone and buprenorphine require daily dosing and have adverse effects. Monthly injectable naltrexone (XR‐NTX) mitigates these adverse effects but is not recommended during pregnancy due to limited pharmacokinetic and safety data. This study developed a physiologically based pharmacokinetic (PBPK) model to describe XR‐NTX pharmacokinetics during pregnancy, and to predict dosing recommendations. Model predictions were successfully validated with observed data. Maternal plasma XR‐NTX profiles were simulated for 400 non‐pregnant virtual females at the approved dose of 380 mg, then randomized to continue with either 380, 285, 190, or 95 mg during pregnancy. The non‐pregnant virtual females had a mean predicted Cmax, AUC0‐7days, and AUC0‐28days of 23.3 ng/mL, 142 ng·d/mL, and 148 ng·d/mL, respectively. Maternal XR‐NTX exposure (AUC0‐28days) were predicted to increase by 1.37, 1.43, and 1.72 times during the first, second, and third trimester of pregnancy. However, the fetal‐to‐maternal exposure (AUC0‐28days) was lower in the first (15%), second (7%), and third (9%) trimesters. A dose of 285 mg of XR‐NTX in pregnancy during the first/second trimester and dose of 190 mg in the third trimester were predicted to provide maternal exposures that were comparable to non‐pregnant levels at the standard dose. This study provides crucial insights into XR‐NTX pharmacokinetics and proposes a dosing strategy during pregnancy, potentially aiding further clinical investigations and decision making regarding XR‐NTX use during pregnancy. [ABSTRACT FROM AUTHOR]