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The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly‐d,l‐Lactic Acid (PDLLA) and/or Polycaprolactone (PCL‐1 or PCL‐2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97–100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre‐dose respiratory rate (RR). The BIOPIN NTX‐implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 μg/kg and especially at 120 μg/kg. Bioabsorbable, extended‐release BIOPIN naltrexone implants are effective in mitigating fentanyl‐induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl‐induced respiratory depression in humans. [ABSTRACT FROM AUTHOR]

This study evaluated the association between medication for opioid use disorder (MOUD) and health care utilization over time among a sample of treatment-seeking individuals with opioid use disorder. In contrast to previous studies, this study used a novel measure of MOUD adherence, more comprehensive utilization data, and analyses that controlled for detailed individual and social determinants of health. This study was a secondary analysis of a comparative effectiveness trial (N=570) of extended-release naltrexone versus buprenorphine-naloxone. The outcome of interest was usage of nonstudy acute care, inpatient and outpatient addiction services, and other outpatient services across 36 weeks of assessment. Adherence (percentage of days taking MOUD) was defined as low (<20%), medium (≥20% but <80%), or high (≥80%). A two-part model evaluated the probability of utilizing a resource and the quantity (utilization days) of the resource consumed. A time-varying approach was used to examine the effect of adherence in a given month on utilization in the same month, with analyses controlling for a wide range of person-level characteristics. Participants with high adherence (vs. low) were significantly less likely to use inpatient addiction (p<0.001) and acute care (p<0.001) services and significantly more likely to engage in outpatient addiction (p=0.045) and other outpatient (p=0.042) services. These findings reinforce the understanding that greater MOUD adherence is associated with reduced usage of high-cost health services and increased usage of outpatient care. The results further suggest the need for enhanced access to MOUD and for interventions that improve adherence. [ABSTRACT FROM AUTHOR]

Background and Objectives: Posttraumatic stress disorder (PTSD) is highly comorbid with substance use disorders (SUD) and can impede SUD recovery. Residential SUD treatment is a crucial opportunity to address PTSD. However, PTSD treatment is lacking in residential SUD care. Methods: We conducted a nonrandomized feasibility study of Written Exposure Therapy (WET), a brief, evidence‐based treatment for PTSD, with patients in residential SUD treatment. We assessed attitudes towards treatment (Credibility and Expectancy Questionnaire, Barriers to Treatment Participation Scale) and mental health indicators (PTSD Checklist for DSM‐5, Trauma Coping Self‐Efficacy, Difficulties in Emotion Regulation‐Short Form, and Brief Assessment of Recovery Capital). Results: Thirty of 49 eligible participants completed WET (61%) and 92% (n = 45) attended at least one WET session. Paired sample t‐tests revealed significant posttreatment improvement across all mental health indicators, with medium to large effect sizes. Discussion and Conclusions: Attendance and completion rates compared favorably to prior exposure‐based treatment for PTSD in SUD settings. Although causality cannot be inferred without a randomized controlled trial, mental health indicators, including PTSD, improved significantly following WET. Scientific Significance: These findings provide evidence that PTSD can be successfully treated in short‐term residential care using brief exposure‐based interventions, which is a crucial clinical need that has been minimally studied in the past. [ABSTRACT FROM AUTHOR]

Background: Evidence-based interventions for treating opioid use disorder (OUD) in youth are limited and little is known about specific and general mechanisms of OUD treatments and how they promote abstinence. Methods: The present study used data from the NIDA-CTN-0010 trial to evaluate the mediating effects of psychosocial treatment-related variables (therapy dose and therapeutic alliance) on end-of-treatment opioid abstinence in a sample of youth with OUD (n = 152, 40% female, mean age = 19.7 years) randomized to receive either 12-weeks of treatment with Bup/Nal ("Bup-Nal") or up to 2 weeks of Bup/Nal detoxification ("Detox") with both treatment arms receiving weekly individual and group drug counseling +/- family therapy. Results: Participants in the Bup-Nal group attended more therapy sessions (16 vs 6 sessions), had increased therapeutic alliance at week-4, and had less opioid use by week-12 compared to those in the Detox group. In both treatment arms, youth who attended more therapy sessions were less likely to have a week-12 opioid positive urine. In a multiple mediator model, therapy dose mediated the association between treatment arm and opioid abstinence. Conclusions: These findings provide preliminary support for a "dose-response" effect of addiction-focused therapy on abstinence in youth OUD. Further, the results identified a mediating effect of therapy dose on the relationship between treatment assignment and opioid treatment outcomes, suggesting that extended Bup-Nal treatment may enhance abstinence, in part, through a mechanism of therapy facilitation, by increasing therapy dose during treatment. Highlights * Therapy dose is associated with lower opioid use in youth treated for OUD with buprenorphine and psychosocial interventions, regardless of the length of buprenorphine medication treatment (ie, 2-week detoxification vs 12-week maintenance dosing). * Participants receiving extended buprenorphine medication treatment attended more therapy sessions and had higher therapeutic alliance than those receiving short-term buprenorphine during a 2-week detoxification. * Therapy dose mediates the relationship between extended vs short-term buprenorphine medication treatment and end-of-treatment opioid use outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up. Design: A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014-17. Setting: Eight community addiction treatment programs in the United States. Participants: English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%). Intervention(s): Participants were treated with daily sublingual buprenorphine-naloxone (BUP-NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use. Measurements: Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP-NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant. Findings: We estimated that increasing BUP-NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = -32.17, -6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6. Conclusions: In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine-naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2. [ABSTRACT FROM AUTHOR]

The article focuses on the opioid crisis in Maryland and the available treatments for opioid use disorder (OUD). Topics include the increase in access to treatment in Maryland, the success of primary care treatment, and the role of telehealth in treating OUD. The article also highlights the intersection between addiction and involvement in the criminal justice system and the resistance to uptake of OUD treatment in detention centers.

The article focuses on the opioid use disorder (OUD) problem in adolescents and young adults highlighting their developmental vulnerability to substance use disorders (SUD). Topics include developmental vulnerability and prevention, standard treatment, and innovative models such as the Youth Opioid Recovery Support (YORS) model that aims to address barriers to treatment engagement in young adults including difficulties with medication adherence.

AbstractObjective: Adverse Childhood Events (ACEs) are associated with increased vulnerability for posttraumatic stress disorder (PTSD), but not everyone who experiences ACEs develops PTSD. Impulsivity has gained interest as a potential mediator between ACEs and PTSD, given that both PTSD and ACEs have been closely related to impulsivity. However, less is known about the relationship within the context of substance use disorder (SUD), a population highly vulnerable to co-occurring PTSD. This study examined whether impulsivity mediates the relationship between ACEs and PTSD symptoms in adults seeking residential treatment for substance use disorder (SUD). Methods: N = 134 consenting adults in residential treatment for SUD completed questionnaires measuring impulsivity (UPPS-P), ACEs (ACEs Scale), and PTSD symptoms (PCL-5). Regression models tested our hypotheses that ACEs would predict PTSD symptoms and that impulsivity would mediate this relationship. Results: Two-thirds of participants met the PCL-5 score threshold for a provisional diagnosis of PTSD. ACEs score and impulsivity were significant direct predictors of PTSD symptoms (coeff = 2.23, p < .001; coeff = 1.03, p < .001). Among UPPS-P subconstructs, only lack of premeditation emerged as a partial mediator (z = 2.14, p = 0.032). Conclusions: Individuals with SUD experience adverse and traumatic events at alarming rates and are at increased risk for PTSD. Our mediation finding suggests that impulsivity and especially lack of premeditation may be clinically relevant in the development or maintenance of PTSD symptoms among individuals with SUD. [ABSTRACT FROM AUTHOR]

This article introduces the Relationship-Oriented Recovery System for Youth (RORSY) protocol, which is designed to increase uptake of Medications for Opioid Use Disorder (MOUD) and related services among adolescents and young adults. Youth exhibit alarmingly poor rates of MOUD initiation and adherence, OUD services involvement and long-term recovery success. RORSY attends to three developmentally unique recovery needs of this age group: assess and bolster youth recovery capital, prioritize involvement of concerned significant others, and use digital direct-to-consumer recovery supports. RORSY contains five evidence-informed intervention modules that can be flexibly tailored to meet the individual and relationship needs of a given youth: Relational Orientation, Youth Recovery Management Planning, Relational Recovery Management Planning, Relationship Skills Building, and Digital Recovery Support Planning. The article concludes with practice and policy recommendations for making relationship-building a top clinical priority for addressing youth OUD.