The Impact of High-Potency Synthetic Opioids on Pharmacotherapies for Opioid Use Disorder: A Scoping Review.

BACKGROUND: The clinical implications of high potency synthetic opioids (HPSO) on medications for opioid use disorder (MOUDs) are not well understood. Although pharmacological interactions are plausible, the clinical significance of such interaction has not been systematically elucidated. This scoping review investigates the relationship between HPSO exposure and various MOUD treatment outcomes. METHODS: We followed PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews) for scoping reviews with extensive a priori search strategy of databases: MEDLINE, EMBASE, PsycINFO, Web of Science, CINAHL, and Cochrane. RESULTS: From 9149 studies, 34 fulfilled the inclusion criteria. Synthesized data reveal several critical insights: First, there is a variable but high occurrence (38%-80%) of HPSO usage among individuals with MOUDs. Second, MOUDs are linked to a decreased risk of overdoses and deaths associated with HPSO. Third, HPSO consumption is correlated with the risk of precipitated withdrawal when starting buprenorphine. Fourth, low-dose buprenorphine is being recognized as one method to avoid moderate withdrawal symptoms prior to treatment. Lastly, significant gaps exist in human experimental data concerning the effects of HPSO on key factors critical for treating OUD-craving, withdrawal symptoms, and pain. CONCLUSIONS: Current evidence supports MOUD safety and effectiveness in reducing nonmedical opioid use. Further research is needed to explore HPSO's influence on the acute factors preceding nonmedical opioid use, such as cravings, withdrawal symptoms, and pain. This research could inform the optimization of MOUD dosing strategies. Achieving consensus and harmonizing data across clinical and research protocols could diminish variability, enhancing our understanding of HPSOs effect on MOUD treatment outcomes.

Prenatal opioid exposure significantly impacts placental protein kinase C (PKC) and drug transporters, leading to drug resistance and neonatal opioid withdrawal syndrome.

Background: Neonatal Opioid Withdrawal Syndrome (NOWS) is a consequence of in-utero exposure to prenatal maternal opioids, resulting in the manifestation of symptoms like irritability, feeding problems, tremors, and withdrawal signs. Opioid use disorder (OUD) during pregnancy can profoundly impact both mother and fetus, disrupting fetal brain neurotransmission and potentially leading to long-term neurological, behavioral, and vision issues, and increased infant mortality. Drug resistance complicates OUD and NOWS treatment, with protein kinase regulation of drug transporters not fully understood. Methods: DNA methylation levels of ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, along with protein kinase C (PKC) genes, were assessed in 96 placental samples using the Illumina Infinium MethylationEPIC array (850K). Samples were collected from three distinct groups: 32 mothers with infants prenatally exposed to opioids who needed pharmacological intervention for NOWS, 32 mothers with prenatally opioid-exposed infants who did not necessitate NOWS treatment, and 32 mothers who were not exposed to opioids during pregnancy. Results: We identified 69 significantly differentially methylated SLCs, with 24 hypermethylated and 34 hypomethylated, and 11 exhibiting both types of methylation changes including SLC13A3, SLC15A2, SLC16A11, SLC16A3, SLC19A2, and SLC26A1. We identified methylation changes in 11 ABC drug transporters (ABCA1, ABCA12, ABCA2, ABCB10, ABCB5, ABCC12, ABCC2, ABCC9, ABCE1, ABCC7, ABCB3): 3 showed hypermethylation, 3 hypomethylation, and 5 exhibited both. Additionally, 7 PKC family genes (PRKCQ, PRKAA1, PRKCA, PRKCB, PRKCH, PRKCI, and PRKCZ) showed methylation changes. These genes are associated with 13 pathways involved in NOWS, including ABC transporters, bile secretion, pancreatic secretion, insulin resistance, glutamatergic synapse, and gastric acid secretion. Conclusion: We report epigenetic changes in PKC-related regulation of drug transporters, which could improve our understanding of clinical outcomes like drug resistance, pharmacokinetics, drug-drug interactions, and drug toxicity, leading to maternal relapse and severe NOWS. Novel drugs targeting PKC pathways and transporters may improve treatment outcomes for OUD in pregnancy and NOWS.

Facilitation and Preferred Models for Delivering Substance Use Disorder Treatment in HIV Clinics: Results From a Multisite Randomized Trial.

BACKGROUND: Integrated addiction treatment in HIV clinics is associated with improved outcomes, yet it is offered inconsistently and with variable models of care. We sought to evaluate the impact of Implementation Facilitation ("Facilitation") on clinician and staff preference for provision of addiction treatment in HIV clinics with on-site resources (all trained or designated on-site specialist) versus outside resources (outside specialist or refer out). METHODS: From July 2017 to July 2020, surveys assessed clinician and staff preferences for addiction treatment models during control (ie, baseline), intervention, evaluation, and maintenance phases in 4 HIV clinics in the Northeast United States. RESULTS: During the control phase, among 76 respondents (response rate, 58%), the proportions who preferred treatment with on-site resources for opioid use disorder (OUD), alcohol use disorder (AUD), and tobacco use disorder (TUD) were 63%, 55%, and 63%, respectively. Compared with control, there were no significant differences in preferred model during the intervention and evaluation phases except for AUD where there was an increased preference for treatment with on-site resources in the intervention versus control phase. Compared with control, during the maintenance phase, a higher proportion of clinicians and staff preferred providing addiction treatment with on-site resources versus outside resources: OUD, 75% (odds ratio [OR; 95% confidence interval {CI}], 1.79 [1.06-3.03]); AUD, 73% (OR [95% CI], 2.23 [1.36-3.65]), and TUD, 76% (OR [95% CI], 1.88 [1.11-3.18]). CONCLUSIONS: The findings from this study lend support for "Facilitation" as a strategy to enhance clinician and staff preference for integrated addiction treatment in HIV clinics with on-site resources.

Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome.

Introduction: The neonate exposed to opioids in utero faces a constellation of withdrawal symptoms postpartum commonly called neonatal opioid withdrawal syndrome (NOWS). The incidence of NOWS has increased in recent years due to the opioid epidemic. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. Epigenetic variations in microRNAs (miRNAs) and their impact on addiction-related processes is a rapidly evolving area of research. Methods: The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls. Results: The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis. Conclusion: This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well.

Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons.

Background: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights. Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications. Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers. Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances. Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment.

Effect of Implementation Facilitation to Promote Adoption of Medications for Addiction Treatment in US HIV Clinics: A Randomized Clinical Trial.

Importance: Medications for addiction treatment (MAT) are inconsistently offered in HIV clinics. Objective: To evaluate the impact of implementation facilitation (hereafter referred to as "facilitation"), a multicomponent implementation strategy, on increasing provision of MAT for opioid use disorder (MOUD), alcohol use disorder (MAUD), and tobacco use disorder (MTUD). Design, Setting, and Participants: Conducted from July 26, 2016, through July 25, 2020, the Working with HIV Clinics to adopt Addiction Treatment using Implementation Facilitation (WHAT-IF?) study used an unblinded, stepped wedge design to sequentially assign each of 4 HIV clinics in the northeastern US to cross over from control (ie, baseline practices) to facilitation (ie, intervention) and then evaluation and maintenance periods every 6 months. Participants were adult patients with opioid, alcohol, or tobacco use disorder. Data analysis was performed from August 2020 to September 2022. Interventions: Multicomponent facilitation. Main Outcomes and Measures: Outcomes, assessed using electronic health record data, were provision of MAT among patients with opioid, alcohol, or tobacco use disorder during the evaluation (primary outcome) and maintenance periods compared with the control period. Results: Among 3647 patients, the mean (SD) age was 49 (12) years, 1814 (50%) were Black, 781 (22%) were Hispanic, and 1407 (39%) were female; 121 (3%) had opioid use disorder, 126 (3%) had alcohol use disorder, and 420 (12%) had tobacco use disorder. Compared with the control period, there was no increase in provision of MOUD with facilitation during the evaluation period (243 patients [27%; 95% CI, 22%-32%] vs 135 patients [28%; 95% CI, 22%-35%]; P = .59) or maintenance period (198 patients [29%; 95% CI, 22%-36%]; P = .48). The change in provision of MAUD from the control period to the evaluation period was not statistically significant (251 patients [8%; 95% CI, 5%-12%] vs 112 patients [13%; 95% CI, 8%-21%]; P = .11); however, the difference increased and became significant during the maintenance period (180 patients [17%; 95% CI, 12%-24%]; P = .009). There were significant increases in provision of MTUD with facilitation during both the evaluation (810 patients [33%; 95% CI, 30%-36%] vs 471 patients [40%; 95% CI, 36%-45%]; P = .005) and maintenance (643 patients [38%; 95% CI, 34%-41%]; P = .047) periods. Conclusions and Relevance: In this randomized clinical trial, facilitation led to increased provision of MTUD, delayed improvements in MAUD, and no improvements in MOUD in HIV clinics. Enhanced strategies, potentially including clinic and patient incentives, especially for MOUD, may be needed to further increase provision of MAT in HIV clinics. Trial Registration: ClinicalTrials.gov Identifier: NCT02907944.

Patients' perspectives of medications for addiction treatment in HIV clinics: A qualitative study.

BACKGROUND: While substance use disorders (SUD) disproportionately impact people with HIV (PWH), HIV clinics inconsistently provide evidence-based medications for addiction treatment (MAT). Patient receptivity to MAT is critical to enhance addiction treatment in these settings. However, we know little from patients about how to best integrate MAT into HIV clinics. METHODS: This qualitative study used four focus groups informed by the Promoting Action on Research Implementation in Health Services framework to identify barriers and facilitators to receiving opioid, alcohol, and tobacco use disorder care in HIV clinics. The study population included 28 patients with HIV and SUD receiving care at one of four HIV clinics in the northeastern United States. Focus groups were recorded and transcribed for content analysis. The study also performed a brief survey assessing demographics and behaviors. RESULTS: Focus groups revealed several major themes related to MAT in HIV clinics. Barriers included stigma around MAT, knowledge deficits about available MAT options and the impact of substance use on PWH, concerns about medication side effects, substance use screening without adequate clinician follow-up, and peers who discouraged MAT. Facilitators included recognition of substance use as a threat to overall health, integrated care from HIV clinicians, and support for addiction treatment from peers with lived experience. CONCLUSIONS: Efforts to enhance MAT in HIV clinics should include patient education to help them recognize addiction as a chronic disease with available medication treatment options; clinician and staff training to promote integrated, multidisciplinary screening and treatment; and thoughtful inclusion of peers with lived experience.

Maternal opioid use disorder: Placental transcriptome analysis for neonatal opioid withdrawal syndrome.

Excessive prenatal opioid exposure may lead to the development of Neonatal Opioid Withdrawal Syndrome (NOWS). RNA-seq was done on 64 formalin-fixed paraffin-embedded placental tissue samples from 32 mothers with opioid use disorder, with newborns with NOWS that required treatment, and 32 prenatally unexposed controls. We identified 93 differentially expressed genes in the placentas of infants with NOWS compared to unexposed controls. There were 4 up- and 89 downregulated genes. Among these, 7 genes CYP1A1, APOB, RPH3A, NRXN1, LINC01206, AL157396.1, UNC80 achieved an FDR p-value of <0.01. The remaining 87 genes were significant with FDR p-value <0.05. The 4 upregulated, CYP1A1, FP671120.3, RAD1, RN7SL856P, and the 10 most significantly downregulated genes were RNA5SP364, GRIN2A, UNC5D, DMBT1P1, MIR3976HG, LINC02199, LINC02822, PANTR1, AC012178.1, CTNNA2. Ingenuity Pathway Analysis identified the 7 most likely to play an important role in the etiology of NOWS. Our study expands insights into the genetic mechanisms of NOWS development.

The effect of varenicline on smoking and drinking outcomes among Black and White adults with alcohol use disorder and co-occurring cigarette smoking: A secondary analysis of two clinical trials.

INTRODUCTION: Varenicline is an FDA-approved medication for smoking cessation and has demonstrated promise in reducing alcohol use. This study sought to compare the efficacy of varenicline in reducing smoking and drinking among Black and White people seeking alcohol treatment. METHODS: Linear mixed modeling was conducted using data from two multi-site placebo-controlled randomized clinical trials examining the effects of varenicline for treatment of Alcohol Use Disorder (AUD; O'Malley et al., 2018; Litten et al., 2013) among Black and White adults with AUD and co-occurring cigarette smoking. The primary analyses were conducted in a sample of 117 adults (O'Malley trial: 29.1% female, 55.2% Black), and replicated in an independent sample of 73 adults (Litten trial: 23.3% female, 45.2% Black). RESULTS: Black participants smoked fewer cigarettes per day compared to White participants (O'Malley trial: F1,116 = 8.95, p = .003; Litten trial: F1,68.9 = 4.74p = .03). Linear mixed models revealed a marginal effect of varenicline on reducing cigarettes smoked per day regardless of race in the O'Malley trial (F1,109 = 3.34, p = .07), which was replicated in the Litten trial (F1,67.1 = 20.77p < .0001). Participants reduced the number of drinks consumed regardless of treatment condition or race in both trials (O'Malley trial: F1,98 = 131.69, p < .0001; Litten trial:F1,69 = 60.36, p < .0001). CONCLUSIONS: Our adjusted model findings suggest varenicline reduced smoking among Black and White people with AUD and co-occurring cigarette smoking. However, these findings should be replicated in a larger sample.

Readiness to Provide Medications for Addiction Treatment in HIV Clinics: A Multisite Mixed-Methods Formative Evaluation.

BACKGROUND: We sought to characterize readiness, barriers to, and facilitators of providing medications for addiction treatment (MAT) in HIV clinics. SETTING: Four HIV clinics in the northeastern United States. METHODS: Mixed-methods formative evaluation conducted June 2017-February 2019. Surveys assessed readiness [visual analog scale, less ready (0-<7) vs. more ready (≥7-10)]; evidence and context ratings for MAT provision; and preferred addiction treatment model. A subset (n = 37) participated in focus groups. RESULTS: Among 71 survey respondents (48% prescribers), the proportion more ready to provide addiction treatment medications varied across substances [tobacco (76%), opioid (61%), and alcohol (49%) treatment medications (P values < 0.05)]. Evidence subscale scores were higher for those more ready to provide tobacco [median (interquartile range) = 4.0 (4.0, 5.0) vs. 4.0 (3.0, 4.0), P = 0.008] treatment medications, but not significantly different for opioid [5.0 (4.0, 5.0) vs. 4.0 (4.0, 5.0), P = 0.11] and alcohol [4.0 (3.0, 5.0) vs. 4.0 (3.0, 4.0), P = 0.42] treatment medications. Median context subscale scores ranged from 3.3 to 4.0 and generally did not vary by readiness status (P values > 0.05). Most favored integrating MAT into HIV care but preferred models differed across substances. Barriers to MAT included identification of treatment-eligible patients, variable experiences with MAT and perceived medication complexity, perceived need for robust behavioral services, and inconsistent availability of on-site specialists. Facilitators included knowledge of adverse health consequences of opioid and tobacco use, local champions, focus on quality improvement, and multidisciplinary teamwork. CONCLUSIONS: Efforts to implement MAT in HIV clinics should address both gaps in perspectives regarding the evidence for MAT and contextual factors and may require substance-specific models.

Placental DNA methylation profiles in opioid-exposed pregnancies and associations with the neonatal opioid withdrawal syndrome.

Opioid abuse during pregnancy can result in Neonatal Opioid Withdrawal Syndrome (NOWS). We investigated genome-wide methylation analyses of 96 placental tissue samples, including 32 prenatally opioid-exposed infants with NOWS who needed therapy (+Opioids/+NOWS), 32 prenatally opioid-exposed infants with NOWS who did not require treatment (+Opioids/-NOWS), and 32 prenatally unexposed controls (-Opioids/-NOWS, control). Statistics, bioinformatics, Artificial Intelligence (AI), including Deep Learning (DL), and Ingenuity Pathway Analyses (IPA) were performed. We identified 17 dysregulated pathways thought to be important in the pathophysiology of NOWS and reported accurate AI prediction of NOWS diagnoses. The DL had an AUC (95% CI) =0.98 (0.95-1.0) with a sensitivity and specificity of 100% for distinguishing NOWS from the +Opioids/-NOWS group and AUCs (95% CI) =1.00 (1.0-1.0) with a sensitivity and specificity of 100% for distinguishing NOWS versus control and + Opioids/-NOWS group versus controls. This study provides strong evidence of methylation dysregulation of placental tissue in NOWS development.

Multiple Psychiatric Morbidity and Continued Use of Naltrexone for Alcohol Use Disorder.

BACKGROUND AND OBJECTIVES: Despite substantial evidence of the efficacy of naltrexone in treating alcohol use disorder (AUD), naltrexone is used infrequently and often for short durations. Understanding factors related to the initiation and continued use of naltrexone could identify targets for improving its use in clinical practice. METHODS: We used the Fiscal year 2012 national data from the Veterans Health Administration to identify the proportion of veterans diagnosed with AUD who initiated and then continued to receive naltrexone for AUD over a 6-month period (N = 67,788). We further examined correlates of any use and continued use, and patterns of use in inpatient and outpatient mental health services and psychotropic prescription fills. Comparisons were made using bivariate analyses and multinomial logistic regression. RESULTS: Among the veterans diagnosed with AUD, 2.02% initiated treatment with naltrexone. Naltrexone initiation was associated with recent homelessness, concurrent psychiatric disorders, receipt of psychiatric outpatient services, psychotropic prescription fills, residential treatment, and psychiatric and medical-surgical hospitalization. Of the 1,366 patients initiating naltrexone, 43.2% (590) received 2 to 5 prescriptions and 16.3% (223) received more than 5 prescriptions for naltrexone. Use of naltrexone beyond one prescription was associated with homelessness, major depressive disorder, schizophrenia, psychotropic medication use, and psychiatric hospitalization. CONCLUSION: Veterans with AUD who used and continued naltrexone were primarily those with multimorbidity and extensive involvement in psychiatric treatment. SCIENTIFIC SIGNIFICANCE: Prior studies examined the correlates of initiation of naltrexone but retention in treatment has received less attention. This study identified the frequency and important patient and service correlates of continued use of naltrexone. (Am J Addict 2021;30:55-64).

Working with HIV clinics to adopt addiction treatment using implementation facilitation (WHAT-IF?): Rationale and design for a hybrid type 3 effectiveness-implementation study.

BACKGROUND: Tobacco, alcohol and opioid misuse are associated with substantial morbidity and mortality among people with HIV (PWH). Despite existence of evidence-based counseling and medications for addiction, these treatments are infrequently offered in HIV clinics. The Working with HIV clinics to adopt Addiction Treatment using Implementation Facilitation (WHAT-IF?) study was conducted to address this implementation challenge. The study's goals were to conduct a formative evaluation of barriers to and facilitators of implementing addiction treatment for PWH followed by an evaluation of the impact of Implementation Facilitation (IF) on promoting adoption of addiction treatments and clinical outcomes. METHODS: The study was conducted at four HIV clinics in the northeast United States, using a hybrid type 3 effectiveness-implementation stepped wedge design and guided by the Promoting Action on Research Implementation in Health Services Research (PARiHS) framework. A mixed-methods approach was used to identify evidence, context, and facilitation-related barriers to and facilitators of integration of addiction treatments into HIV clinics and to help tailor IF for each clinic. An evaluation was then conducted of the impact of IF on implementation outcomes, including provision of addiction treatment (primary outcome), organizational and clinician and staff readiness to adopt addiction treatment, and changes in organizational models of care used to deliver addiction treatment. The evaluation also included IF's impact on effectiveness outcomes, specifically HIV-related outcomes among patients eligible for addiction treatment. CONCLUSIONS: Results will generate important information regarding the impact of IF as a reproducible strategy to promote addiction treatment in HIV clinics.

Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline.

BACKGROUND: The alcohol cue reactivity paradigm is increasingly used to screen medications for the treatment of alcohol use disorder (AUD) and other substance use disorders. Yet, its prospective association with craving and naturalistic drinking outcomes in clinical trials remains unknown. This study embedded repeated human laboratory assessments of alcohol cue reactivity within the context of a randomized controlled trial to examine the effects of varenicline tartrate (Chantix® ), a partial agonist of α4ß2 nicotinic acetylcholine receptors, on alcohol craving among treatment-seeking heavy drinkers with AUD. Our main objectives were to test whether varenicline, as compared to placebo, blunts alcohol cue-elicited craving and test whether alcohol cue reactivity observed in the human laboratory predicts subsequent alcohol craving and use during the remainder of the trial. DESIGN AND METHODS: This double-blind, randomized, 2-site study compared the effects of varenicline (up to 2 mg/d) and placebo on responses to in vivo alcohol cue and affective picture cue exposure in the human laboratory. Forty-seven volunteers (18 females, 29 males), ages 23 to 67 years (M = 43.7, SD = 11.5), were recruited from the community via advertisements to participate in a clinical trial designed to study the effects of varenicline on alcohol use. Participants were randomized to either varenicline or placebo for 6 weeks. RESULTS: Varenicline did not attenuate cue-induced alcohol craving relative to placebo, but craving captured during the cue reactivity paradigm significantly predicted subsequent alcohol use in real-world settings during the clinical trial. Higher craving predicted heavier alcohol use. CONCLUSIONS: Our results are among the first to show alcohol cue-induced craving captured during a human laboratory paradigm predicts drinking outcomes in the context of a clinical trial.

Stitching a solution to the addiction epidemic: A longitudinal addiction curricular thread across four years of medical training.

BACKGROUND: Despite the enormous burden and public health impact, addiction continues to be one of the most under-treated chronic diseases primarily because of the lack of adequately trained work force of medical providers. To address this issue, medical schools should greatly expand education on addiction. Methods: The six-step Kern model of curriculum development was used as a framework to create an addiction curriculum which includes didactic activities, workshop exercises, practice-based learning activities, clinical simulations, and clinical experiences. Results: The authors and other members of the addiction thread committee conducted a comprehensive needs assessment, developed curriculum goals and objectives, and worked with course and clerkship directors to develop and enhance educational strategies and implement a longitudinal curricular thread woven across all four years of medical school curriculum. Conclusion: Development and implementation of a comprehensive addiction curriculum is feasible, and this model could lay the ground work for implementation at other institutions.

Medications for Maintenance Treatment of Opioid Use Disorder in Adolescents: A Narrative Review and Assessment of Clinical Benefits and Potential Risks.

OBJECTIVE: Methadone, buprenorphine, and naltrexone are evidence-based treatments for opioid use disorder (OUD). A large body of evidence supports their effectiveness in adults with OUD. However, few studies have tested their efficacy in adolescents. This study summarizes the clinical benefits and risks of three medications for the treatment of OUD in adolescents. METHOD: We review and synthesize the published evidence about the efficacy and potential risks (including safety concerns) associated with methadone, buprenorphine, or naltrexone for the treatment of OUD in adolescents and compare their benefits and risks with that of no treatment or treatment without medications. We also discuss adolescent-specific treatment needs and strategies to overcome potential challenges in prescribing medications for adolescents with OUD. RESULTS: Methadone appears to be effective in promoting treatment retention among adolescents with heroin use disorder. Data from three randomized controlled trials suggest that buprenorphine treatment improves the likelihood of opioid abstinence and treatment retention. Although these medications have a potential risk of overdose when misused or used illegally, evidence suggests this risk is much lower for buprenorphine than methadone. Emerging data also suggest that naltrexone is a safe and feasible option for adolescents. Vast evidence demonstrates that the risks of untreated OUD far outweigh the risks of any of the previously discussed medications. CONCLUSIONS: Little published evidence specifically examines the efficacy and safety of using medications for OUD in adolescents, and more research is needed. It is essential for healthcare professionals to determine whether their adolescent patients may benefit from medications for the treatment of OUD.

Randomized Clinical Trial of Computerized and Clinician-Delivered CBT in Comparison With Standard Outpatient Treatment for Substance Use Disorders: Primary Within-Treatment and Follow-Up Outcomes.

OBJECTIVE: Previous trials have demonstrated the efficacy and durability of computer-based cognitive-behavioral therapy (CBT4CBT) as an add-on to standard outpatient care in a range of treatment-seeking populations. In this study, the authors evaluated the efficacy and safety of CBT4CBT as a virtual stand-alone treatment, delivered with minimal clinical monitoring, and clinician-delivered cognitive-behavioral therapy (CBT) compared with treatment as usual in a heterogeneous sample of treatment-seeking outpatients with substance use disorders. METHOD: This was a randomized clinical trial in which 137 individuals who met DSM-IV-TR criteria for current substance abuse or dependence were randomly assigned to receive treatment as usual, weekly individual CBT, or CBT4CBT with brief weekly monitoring. RESULTS: Rates of treatment exposure differed by group, with the best retention in the CBT4CBT group and the poorest in the individual CBT group. Participants who received CBT or CBT4CBT reduced their frequency of substance use significantly more than those who received treatment as usual. Six-month follow-up outcomes indicated continuing benefit of CBT4CBT (plus monitoring) over treatment as usual, but not for clinician-delivered CBT over treatment as usual. Analysis of secondary outcomes indicated that participants in the CBT4CBT group demonstrated the best learning of cognitive and behavioral concepts, as well as the highest satisfaction with treatment. CONCLUSIONS: This first trial of computerized CBT as a virtual stand-alone intervention delivered in a clinical setting to a diverse sample of patients with current substance use disorders indicated that it was safe, effective, and durable relative to standard treatment approaches and was well-liked by participants. Clinician-delivered individual CBT, while efficacious within the treatment period, was unexpectedly associated with a higher dropout rate and lower effects at follow-up.

An Innovative Use of Case Conference to Teach Future Educators in Addiction Psychiatry.

Objective An innovative course was developed for fellows enrolled in the Yale School of Medicine Addiction Psychiatry program to educate them in key principles of adult learning, apply these principles in a case conference presentation, and to improve skills in providing and receiving feedback. Methods An initial training module on educational skills was followed by individual mentorship to prepare a case presentation. A feedback module provided space to learn and practice skills in feedback delivery. Results The program showed positive results and improved confidence levels of the participants in presenting and providing/receiving feedback. Conclusions Implementing a course designed to improve teaching and feedback skills is feasible in a 1-year Addiction Psychiatry fellowship.