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The μ-opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk=0.76, 95% confidence intervals=0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058. Luciferase assays indicated miR-95-3p decreased reporter activity of constructs containing the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect. These findings suggest that selection of a medication for opioid dependence based on rs10485058 genotype might improve outcomes in this ethnic group.

Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted.

BACKGROUND: Patients presenting for treatment of substance use disorders (SUDs) often exhibit medical comorbidities that affect functional health status and healthcare costs. Providing primary care within addictions clinics (onsite care) may improve medical and SUD treatment outcomes in this population. OBJECTIVE: The objective of this study was to compare outcomes among Veterans' Administration (VA) patients who receive medical care within the SUD clinic and those referred to a general medicine clinic at the same facility. METHODS: Veterans entering SUD treatment with a chronic medical condition and no current primary care were randomized to receive primary medical care: 1) onsite in the VA SUD clinic (n = 358), or 2) in the VA general internal medicine clinic (n = 362). Subjects were assessed at baseline and at 3, 6, and 12 months postrandomization. Intention-to-treat analyses used random-effects regression. MEASURES: Measures included SF-36 Physical and Mental Component Summaries (PCS, MCS), VA service utilization, SUD treatment retention, Addiction Severity Index (ASI) scores, 30-day abstinence, and total VA healthcare costs. RESULTS: Over the study year, patients assigned to onsite care were more likely to attend primary care (adjusted odds ratio [OR] = 2.20; 95% confidence interval [CI] = 1.53-3.15) and to remain engaged in SUD treatment at 3 months (adjusted OR = 1.36; 1.00-1.84). Overall, outcomes on the MCS (but not the PCS) and the ASI improved significantly over time but did not differ by treatment condition. Total VA healthcare costs did not differ reliably across conditions. CONCLUSIONS: Compared with referral care, providing primary care within a VA addiction clinic increased primary care access and initial SUD treatment retention but showed no effect on overall health status or costs. [ABSTRACT FROM AUTHOR]

Methamphetamine-dependent inpatients (N = 51) were screened for childhood attention deficit hyperactivity disorder (ADHD) using the Wender Utah Rating Scale upon admission to 30-day inpatient treatment. Baseline assessments included neuropsychological tests of executive function, memory, information processing, verbal fluency, attention, motor skills, and the Brief Symptom Inventory (BSI), a measure of psychiatric symptomatology. The thirty-six participants (70.6%) screening positive for ADHD reported significantly more frequent methamphetamine use prior to baseline. Baseline cognitive functioning was similar between groups, but the presumptive ADHD participants exhibited significantly worse psychiatric symptomatology. At three-week follow- up, 41 participants (80.4%) repeated the neuropsychological battery and BSI. All 10 non-completers screened positive for ADHD. The entire sample improved with abstinence in most neuropsychological domains except memory. The presumptive ADHD group failed to improve on tests of attention. All participants demonstrated significant reductions in psychiatric symptoms with abstinence. Methamphetamine-dependent individuals with ADHD symptoms are common and pose a significant treatment challenge. [ABSTRACT FROM AUTHOR]

We evaluated whether the Alcohol Use Disorders Identification Test (AUDIT) predicted clinically meaningful alcohol withdrawal syndrome (AWS) in 118 alcohol dependent patients without a history of seizures. Patients were monitored by serial administration of the revised Clinical Institute Withdrawal Assessment Scale for Alcohol (CIWA-Ar) during inpatient detoxification. Patients (N = 55) who reached threshold level of AWS for receiving medication (CIWA-Ar > 9) scored significantly higher (p <.001) on the AUDIT total score, the dependence sub-scale, and the single item on morning drinking. Sensitivity, specificity, positive and negative predictive power, and screening efficiency showed the value of the AUDIT for identifying patients who developed AWS. The AUDIT should be explored alone and in combination with other parameters to improve screening for clinically meaningful AWS in other settings. [ABSTRACT FROM AUTHOR]

Objectives: To test the efficacy of providing brief motivational feedback to increase post-incarceration substance use disorders (SUD) treatment contact.Design: Randomized clinical trial (feedback vs. control) with a 2-month post-incarceration follow-up.Participants: Veterans (N = 73) incarcerated in a county jail system who met SUD diagnostic criteria.Measures: Baseline assessment included the Addiction Severity Index, the Form-90 assessment of recent alcohol use, and a DSM-IV SUD criteria checklist. The primary outcome was Veterans Administration (VA) appointments. Secondary outcomes were the Addiction Severity Index-Followup and the Treatment Services Review.Intervention: All participants received baseline assessment. The feedback condition received personalized feedback and encouragement to explore ambivalence about change and treatment in a single interview.Results: Participants receiving feedback were more likely to schedule appointments at a VA addictions clinic within 60 days of their jail release dates (67 vs. 41%; P < 0.03). Though differences were not statistically significant, more feedback participants attended addictions clinic appointments (47 vs. 32%; ns) and were retained in addictions treatment at 90 days (31 vs. 14%; P < 0.08). Treatment appointments were more likely when intervention occurred close to release. Loss of participants to post-release follow-up interviews was >50%, limiting power to detect significant differences by self-report.Conclusion: Brief motivational feedback shows promise as a way to link incarcerated individuals to SUD treatment services. [ABSTRACT FROM AUTHOR]

The two articles presented previously in this volume provide state-of-the-art reviews of the etiology, epidemiology, screening and treatment of substance use disorder (SUD). This article identifies next steps in research and development for understanding and treating SUD in Operation Enduring Freedom/Operation Iraqi Freedom service members and veterans. Four promising areas are reviewed: advances in psychopharmacological treatment of SUD, innovations in behavioral treatments, the use of technological advances for the screening and treatment of SUD, and integration of treatment services. Future directions are explored and suggestions for research, development and implementation of each of these trends are discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although the Veterans Affairs and Department of Defense (VA/DoD) clinical guidelines for management of posttraumatic stress disorder (PTSD) recommend against routine benzodiazepine use, little is known about the trends and clinical and prescription profiles of benzodiazepine use since these guidelines were released in 2004. METHODS: This retrospective study included 64,872 patients with a PTSD diagnosis received from care at facilities in VA Northwest Veterans Integrated Service Network (VISN 20) during 2003-2010. Annual prevalence of any use was defined as any prescription for benzodiazepines, and long-term use was defined as >90 days' supply, in a year. Gender-specific logistic regressions were fit to estimate any and long-term benzodiazepine use, test for linear trends over 8-years and explore factors associated with trends. RESULTS: The trend of age-adjusted benzodiazepine use over 8-years rose significantly from 25.0 to 26.8% among men and 31.2 to 38.8% among women. Long-term use in men and women increased from 15.4 to 16.4% and 18.0 to 22.7%, respectively. Comorbid psychiatric and alcohol use disorders (AUD) were associated with a greater increase in long-term use of benzodiazepines. In 2010, 61% of benzodiazepine users received >90 days' supply. Among those prescribed benzodiazepines long-term, 11% had AUD and 47% were also prescribed opioids long-term. CONCLUSION: Despite VA/DoD clinical guidelines recommending against routine use of benzodiazepines for PTSD, the adjusted prevalence of long-term use increased among men and women with PTSD in VISN 20. Widespread concomitant use of benzodiazepines and opioids suggests risk management systems and research on the efficacy and safety of these medications are needed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Amidst increasing opioid-related overdoses in the USA, opioid use disorder (OUD) treatment has seen few novel treatments emerge. High-potency synthetic opioids (HPSOs) have altered clinical approaches, prompting evaluation of existing medications for opioid use disorder (MOUD) and interest in slow-release oral morphine (SROM) as another therapeutic option. Here we survey addiction specialists on the influence of HPSOs on clinical practice, views on current MOUD regulations, and openness to novel therapies such as SROM., Methods: Anonymous, online survey conducted at a national conference of addiction specialists (N = 91). Pearson χ 2 tests and Fisher's exact tests to compare respondent characteristics., Results: Approximately 89% of respondents (N = 91) acknowledge that HPSOs shifted addiction treatment in recent years, with 86% modifying their MOUD prescribing accordingly. Moreover, 84% report having patients who could benefit from other full opioid agonists beyond methadone for OUD management. Many report off-label prescribing of full agonist opioids other than methadone for withdrawal symptoms or initiating MOUD. Eighty percent reported being in favor of incorporating SROM as a third-line monotherapy for OUD., Discussion and Conclusion: This sample of addiction specialists supports innovative alternatives for MOUD in the USA to combat the challenges posed by fentanyl and related HPSOs. Future work should further addiction specialists' opinions on barriers to OUD treatment and exploration of these international strategies in the USA., Scientific Significance: This appears to be the first study exploring addiction specialists' perspectives on regulatory barriers to OUD treatment and their willingness to uptake internationally adopted strategies such as SROM., (© 2024 The Author(s). The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry (AAAP).)

Introduction: Engagement is a critical component of successful treatment for opioid use disorder (OUD). However, rates of patient engagement in OUD treatment, especially in outpatient settings, are variable and often low. Little is known about the specific strategies members of primary care teams use to initiate and encourage ongoing participation in OUD treatment. In a national cohort of primary care clinics in the U.S., we explored the perspectives of primary care team members on the meaning of and approaches to OUD treatment engagement., Methods: We conducted semi-structured interviews with 35 providers from multidisciplinary primary care teams in an existing national cohort of 13 clinics across seven states. Teams were delivering OUD treatment via the Collaborative Care Model, a model that combines primary care providers (PCP), behavioral health care managers (BHCM) and consulting psychiatric providers (CPP) in a structured way to provide patient-centered, team-based, and measurement-based care. Interview participants included 14 PCPs, 13 BHCMs, and 8 CPPs. Interviews asked open-ended questions about provider experiences and practices that aided or hindered patient engagement in OUD treatment. Interview transcripts were double-coded by trained qualitative researchers and analyzed using a combination of deductive and inductive approaches to identify themes., Results: Two themes emerged that describe provider perspectives on the meaning of engagement: 1) qualifying engagement by the volume of contact with patients, and 2) the need for more multidimensional measures of engagement. Six themes emerged that characterized provider engagement practices: 1) creating an environment of disclosure, 2) normalizing OUD treatment, 3) offering gentle but persistent outreach, 4) providing human connection and encouragement, 5) tailoring treatment to patient needs, and 6) avoiding stigmatizing responses. Analysis identified multiple replicable strategies that providers used to support these engagement practices., Conclusions: Providers consistently apply a range of strategies when trying to engage patients in OUD treatment. Specific engagement strategies used embodied compassion and pragmatism, hallmarks of patient-centered care. Further research is needed to understand the impact of scaling engagement approaches across all care settings., Competing Interests: Declaration of competing interest The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work. The authors did not work with or were otherwise influenced by any external sponsors for this work. Dr. Saxon has received travel support from Alkermes, Inc., consulting fees from Indivior, Inc., and royalties from UpToDate, Inc. Anna Ratzliff, MD, PhD receives royalties from Wiley for her book on integrated care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The gold-standard treatment for opioid use disorder (OUD) is medication for OUD (MOUD). However, less than a quarter of people with OUD initiate MOUD. Expanding the Collaborative Care Model (CoCM) to include primary care patients with OUD could improve access to and initiation of MOUD. This paper presents the methods and baseline sample characteristics of a Hybrid Type 2a trial comparing the effectiveness of CoCM for OUD and co-occurring mental health symptoms (MHS) to CoCM for MHS only., Method: 42 primary care clinics were cluster randomized and 254 primary care patients with OUD and elevated MHS were enrolled. Recruitment was terminated early by the Data and Safety Monitoring Board for futility. Participants completed research assessments at baseline, 3 months, and 6 months. The multiple primary outcomes were past-month number of days of nonmedical opioid use and SF12 Mental Health Component Summary (MCS) scores., Results: MCS scores were over a standard deviation below the national mean (M = 34.5). Nearly half (47.6 %) of participants had previously overdosed in their lifetimes. Three quarters (76.0 %) were already being prescribed MOUD at baseline, only 30.4 % reported non-medical use of opioids, and only 33.9 % reported being bothered by opioid cravings., Conclusion: The unexpectedly high proportion of enrollees already prescribed MOUD at baseline indicates that most patients were in the maintenance rather than acute phase of treatment. Challenges identifying and enrolling patients in the acute phase of OUD treatment implies that intervention effectiveness will depend on its success preventing the discontinuation of MOUD rather than initiating MOUD., Competing Interests: Declaration of competing interest The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work. Dr. Saxon has received travel support from Alkermes, Inc., consulting fees from Indivior, Inc., and royalties from UpToDate, Inc. Dr. Ratzliff receives royalties from Wiley for her book on integrated care., (Published by Elsevier Inc.)

Abstract: The directors of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have proposed new efforts to enable earlier identification and intervention for harmful substance use and its consequences. As editors of The ASAM Principles of Addiction Medicine, we fully support this goal. The word "preaddiction" has been suggested as a diagnostic label to describe individuals who would be targeted for early intervention. In this commentary, we offer that "unhealthy substance use" would be a better descriptor than "preaddiction" and review several potential barriers to be addressed in order to maximize the impact of introducing this new paradigm., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Introduction: Opioid and alcohol use disorders are increasingly being addressed in primary care, yet how medications to treat these disorders are prescribed in rural regions is unknown., Methods: We determined prevalence, types, and duration of medication prescription for opioid and/or alcohol use disorder among adult patients in rural primary clinics. The sample included 1874 adult patients who visited one of six rural primary care sites in the Northeastern and Northwestern United States at least once from October 2019 to January 2021 and had a diagnosis code for opioid use disorder (OUD), alcohol use disorder (AUD), or co-occurring opioid and alcohol use disorder (OUD + AUD) during that time., Results: Patients with OUD + AUD were more likely to be prescribed medication for at least one of these disorders (85.3 %) than patients with OUD only (63.7 %) or AUD only (10.3 %). Further, the OUD + AUD group had the highest number of days on medication (M = 264.7), followed by OUD only (M = 220.5), then the AUD only group (M = 62.5). Only 8.8 % of patients with OUD + AUD were prescribed naltrexone or medication for OUD + AUD to treat both substance use disorders., Conclusions: Medications for treating AUD as well as OUD are available, but few patients with OUD + AUD and even fewer with AUD received pharmacological treatment for AUD. The current work highlights the need for rural clinicians to consider medications for AUD as an important treatment method for patients with AUD only or OUD + AUD., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: There is a growing interest in practice-based implementation research, yet too often research prioritizes and is most successful in academic settings. During a national implementation trial to evaluate the effectiveness of Collaborative Care for co-occurring opioid use and mental health disorders, we lost three of our 11 participating implementation sites, all representing community sites., Method: To better understand needed supports for implementation trial participation, we conducted exit interviews ( n  = 5) with key staff at these community sites. Interview transcripts were double-coded and analyzed using Rapid Assessment Process. Qualitative themes were iteratively reviewed by the study team., Results: Three themes emerged characterizing challenges for community sites, including that: (1) research threatens sites' most precious resource-staff; (2) staff lack comfort with and skills for research; and (3) research participation in its current form does not offer a clear return on investment., Conclusions: Learnings from this work illuminate some of the barriers community sites face when trying to participate in multisite implementation research. An undercurrent of participant perspectives was the belief that community sites like theirs are just not set up to successfully participate in clinical trial research, including population-based implementation trials. Future implementation trials should consider strategies that disrupt traditional approaches, increasing the equitable inclusion of diverse practice settings in implementation research., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work. The authors did not work with or were otherwise influenced by any external sponsors for this work. Andrew J. Saxon has received travel support from Alkermes, Inc., consulting fees from Indivior, Inc., and royalties from UpToDate, Inc. Anna D. Ratzliff, MD, PhD, receives royalties from Wiley for her book on integrated care., (© The Author(s) 2024.)

Background: Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial., Methods: This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts., Results: Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53 % female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95 % CI 4.7, 59.7) more days of OUD treatment relative to usual care., Conclusions: Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment., Competing Interests: Declaration of Competing Interest All authors reviewed and approved the final article. Jennifer F. Bobb has no disclosures. Andrea Altschuler has no disclosures. Hongxiang Qiu has no disclosures. Abigail G. Matthews has no disclosures. Jennifer McCormack has no disclosures. Dr. Campbell has received support managed through her institution from the Industry PMR Consortium, a consortium of companies conducting post marketing studies required by the Food and Drug Administration that assess risks related to opioid analgesic use. Outside of this study, Paige Wartko received funding in the past year from a contract awarded to the Harvard Department of Population Medicine from GlaxoSmithKline to assess medication use in pregnancy and funding from a research contract awarded to Kaiser Permanente Washington Health Research Institute from Syneos Health to conduct Food and Drug Administration-mandated post-marketing research on the risks of opioid analgesic use. Dr. Saxon has received an honorarium from Indivior, Inc., travel support from Alkermes, Inc., and royalties from UpToDate. Onchee Yu received research grant funded by Bayer. Jeffrey Samet has no disclosures. Dr. Boudreau previously received funding from a research contract awarded to Kaiser Permanente Washington Health Research Institute (KPWHRI) from Syneos Health to conduct Food and Drug Administration-mandated post-marketing research on the risks of opioid analgesic use. Dr. Boudreau was an employee of KPWHRI at the time the study was conducted but is now an employee of Genentech, Inc. Amy K. Lee has no disclosures Dr. Glass reports that Pear Therapeutics Inc provided digital therapeutic prescriptions at no cost to Kaiser Permanente Washington during a quality improvement pilot study that he led. Kathrine A. Bradley has no disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Opioid use disorder (OUD) care engagement rates in primary care (PC) settings are often low. Little is known about PC team experiences when delivering OUD treatment and potential factors that influence their capacity to engage patients in treatment. Exploring PC team experiences may inform needed supports that can optimize OUD care delivery and improve outcomes for patients with OUD., Objective: We explored multidisciplinary PC team perspectives on barriers and facilitators to engaging patients in OUD treatment., Design: Qualitative study using in-depth interviews., Participants: Primary care clinical teams., Approach: We conducted semi-structured interviews (n = 35) with PC team members involved in OUD care delivery, recruited using a combination of criterion and maximal variation sampling. Data collection and analysis were informed by existing theoretical literature about patient engagement, specifically that patient engagement is influenced by factors across individual (patient, provider), interpersonal (patient-provider), and health system domains. Interviews were professionally transcribed and doubled-coded using a coding schema based on the interview guide while allowing for emergent codes. Coding was iteratively reviewed using a constant comparison approach to identify themes and verified with participants and the full study team., Key Results: Analysis identified five themes that impact PC team ability to engage patients effectively, including limited patient contact (e.g., phone, text) in between visits, varying levels of provider confidence to navigate OUD treatment discussions, structural factors (e.g., schedules, productivity goals) that limited provider time, the role of team-based approaches in lessening discouragement and feelings of burnout, and lack of shared organizational vision for reducing harms from OUD., Conclusions: While the capacity of PC teams to engage patients in OUD care is influenced across multiple levels, some of the most promising opportunities may involve addressing system-level factors that limit PC team time and collaboration and promoting organizational alignment on goals for OUD treatment., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Aims: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone., Methods: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD)., Results: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial., Conclusion: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial., (Published by Oxford University Press on behalf of Medical Council on Alcohol 2024.)

Background: Substance use disorders (SUDs) are prevalent in the USA yet remain dramatically undertreated. To address this care gap, the Accreditation Council for Graduate Medical Education (ACGME) approved revisions to the Program Requirements for Graduate Medical Education (GME) in Internal Medicine, effective July 1, 2022, requiring addiction medicine training for all internal medicine (IM) residents. The Veterans Health Administration (VHA) is a clinical training site for many academic institutions that sponsor IM residencies. This focus group project evaluated VHA IM residency site directors' perspectives about providing addiction medical education within VHA IM training sites., Objective: To better understand the current state, barriers to, and facilitators of IM resident addiction medicine training at VHA sites., Design: This was a qualitative evaluation based on semi-structured video-based focus groups., Participants: Participants were VHA IM site directors based at a VHA hospital or clinic throughout the USA., Approach: Focus groups were conducted using a semi-structured group interview guide. Two investigators coded each focus group independently, then met to create a final adjudicated coding scheme. Thematic analysis was used to identify key themes., Key Results: Forty-three participants from 38 VHA sites participated in four focus groups (average size: 11 participants). Six themes were identified within four pre-defined categories. Current state of training: most VHA sites offered no formal training in addiction medicine for IM residents. Barriers: addiction experts are often located outside of IM settings, and ACGME requirements were non-specific. Facilitators: clinical champions help support addiction training. Desired next steps: participants desired incentives to train or hire local champions and a pre-packaged didactic curriculum., Conclusions: Developing competent clinical champions and leveraging VHA addiction specialists from non-IM settings would create more addiction training opportunities for IM trainees at VHA sites. These insights can likely be applied to IM training at non-VHA sites., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Medication treatment for opioid use disorder (MOUD) is effective and recommended for outpatient settings. We implemented and evaluated the SUpporting Primary care Providers in Opioid Risk reduction and Treatment (SUPPORT) Center-a quality improvement partnership to implement stepped care for MOUD in 2 Veterans Health Administration (VA) primary care (PC) clinics., Methods: SUPPORT provided a dedicated clinical team (nurse practitioner prescriber and social worker) and stepped care ([1] identification, assessment, referral; [2] MOUD induction; [3] stabilization; and [4] maintenance supporting PC providers [PCPs] to initiate and/or sustain treatment) coupled with ongoing internal facilitation (consultation, trainings, informatics support). Qualitative interviews with stakeholders (PCPs and patients) and meeting notes identified barriers and facilitators to implementation. Electronic health record and patient tracking data measured reach, adoption, and implementation outcomes descriptively., Results: SUPPORT's implementation barriers included the need for an X-waiver, VA's opioid tapering policies, patient and PCP knowledge gaps and PCP discomfort, and logistical compatibility and sustainability challenges for clinics. SUPPORT's dedicated clinical staff, ongoing internal facilitation, and high patient and PCP satisfaction were key facilitators. SUPPORT (January 2019 to September 2021) trained 218 providers; 63 received X-waivers, and 23 provided MOUD (10.5% of those trained). SUPPORT provided care to 167 patients, initiated MOUD for 33, and provided education and naloxone to 72 (all = 0 in year before launch)., Conclusions: SUPPORT reached many PCPs and patients and resulted in small increases in MOUD prescribing and high levels of stakeholder satisfaction. Dedicated clinical staff was key to observed successes. Although resource-intensive, SUPPORT offers a potential model for outpatient MOUD provision., Competing Interests: AJS has received travel support from Alkermes, Inc, and served on an Advisory Board for Indivior, Inc. He receives ongoing royalties from UpToDate, Inc. The other authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Objectives: Buprenorphine, a medication for opioid use disorder (OUD), is underutilized in general medical settings. Further, it is inequitably received by racialized groups and persons with comorbidities. The Veterans Health Administration launched an initiative to increase buprenorphine receipt in primary care. The project's objective was to identify patient-related factors associated with buprenorphine receipt and retention in primary care clinics (n = 18) participating in the initiative., Methods: Retrospective cohort quality improvement evaluation of patients 18 years or older with 2 or more primary care visits in a 1-year period and an OUD diagnosis in the year before the first primary care visit (index date). Buprenorphine receipt was the proportion of patients with OUD who received 1 or more buprenorphine prescriptions from primary care providers during the post-index year and retention the proportion who received buprenorphine for 180 days or longer., Results: Of 2880 patients with OUD seen in primary care, 11.7% (95% confidence interval [CI], 10.6%-12.9%) received buprenorphine in primary care, 58.2% (95% CI, 52.8%-63.3%) of whom were retained on buprenorphine for 180 days or longer. Patients with alcohol use disorder (adjusted odds ratio [AOR], 0.39; 95% CI, 0.27-0.57), nonopioid drug use disorder (AOR, 0.64; 95% CI, 0.45-0.93), and serious mental illness (AOR, 0.60; 95% CI, 0.37-0.97) had lower buprenorphine receipt. Those with an anxiety disorder had higher buprenorphine receipt (AOR, 1.42; 95% CI, 1.04-1.95). Buprenorphine receipt (AOR, 0.55; 95% CI, 0.35-0.87) and 180-day retention (AOR, 0.40; 95% CI, 0.19-0.84) were less likely among non-Hispanic Black patients., Conclusions: Further integration of addiction services in primary care may be needed to enhance buprenorphine receipt for patients with comorbid substance use disorders, and interventions are needed to address disparities in receipt and retention among non-Hispanic Black patients., (Copyright © 2024 American Society of Addiction Medicine.)

Background: Co-occurring substance use disorders (SUDs) among individuals with opioid use disorder (OUD) are associated with additional impairment, overdose, and death. This study examined characteristics of patients who have OUD with and without co-occurring SUDs in rural primary care clinics., Methods: Secondary analysis used electronic health record (EHR) data from six rural primary care clinics, including demographics, diagnoses, encounters, and prescriptions of medication for OUD (MOUD), as well as EHR data from an external telemedicine vendor that provided MOUD to some clinic patients. The study population included all adult patients who had a visit to the participating clinics from October 2019 to January 2021., Results: We identified 1164 patients with OUD; 72.6 % had OUD only, 11.5 % had OUD and stimulant use disorder (OUD + StUD), and 15.9 % had OUD and other non-stimulant substance use disorder (OUD + Other). The OUD + StUD group had the highest rates of hepatitis C virus (25.4 % for OUD + StUD, 17.8 % for OUD + Other, and 7.5 % for OUD Only; p < 0.001) and the highest rates of mental health disorders (78.4 %, 69.7 %, and 59.9 %, respectively; p < 0.001). Compared to the OUD Only group, patients in the OUD + StUD and OUD + Other groups were more likely to receive telehealth services provided by clinic staff, in-clinic behavioral health services, and in-clinic MOUD. The OUD + StUD group had the highest proportion of referrals to the external telemedicine vendor., Conclusions: More than 27 % of patients with OUD in rural primary care clinics had other co-occurring SUDs, and these patients received more healthcare services than those with OUD only. Future studies should examine variations in outcomes associated with these other services among patients with OUD and co-occurring SUDs., Competing Interests: Declaration of competing interest Authors disclosing relevant financial interests, activities, relationships, and affiliations are: A.J.S. receives royalties as a section editor for UpToDate, received travel support from Alkermes, Inc. and consultant fees from Indivior, Inc. L.J.M. receives research support from Aelis Pharma. All other authors report no financial or other possible conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The prevalence and associated overdose death rates from opioid use disorder (OUD) have dramatically increased in the last decade. Despite more available treatments than 20 years ago, treatment access and high discontinuation rates are challenges, as are personalized medication dosing and making timely treatment changes when treatments fail. In other fields such as depression, brief measures to address these tasks combined with an action plan-so-called measurement-based care (MBC)-have been associated with better outcomes. This workgroup aimed to determine whether brief measures can be identified for using MBC for optimizing dosing or informing treatment decisions in OUD., Methods: The National Institute on Drug Abuse Center for the Clinical Trials Network (NIDA CCTN) in 2022 convened a small workgroup to develop consensus about clinically usable measures to improve the quality of treatment delivery with MBC methods for OUD. Two clinical tasks were addressed: (1) to identify the optimal dose of medications for OUD for each patient and (2) to estimate the effectiveness of a treatment for a particular patient once implemented, in a more granular fashion than the binary categories of early or sustained remission or no remission found in The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)., Discussion: Five parameters were recommended to personalize medication dose adjustment: withdrawal symptoms, opioid use, magnitude (severity and duration) of the subjective effects when opioids are used, craving, and side effects. A brief rating of each OUD-specific parameter to adjust dosing and a global assessment or verbal question for side-effects was viewed as sufficient. Whether these ratings produce better outcomes (e.g., treatment engagement and retention) in practice deserves study. There was consensus that core signs and symptoms of OUD based on some of the 5 DSM-5 domains (e.g., craving, withdrawal) should be the basis for assessing treatment outcome. No existing brief measure was found to meet all the consensus recommendations. Next steps would be to select, adapt or develop de novo items/brief scales to inform clinical decision-making about dose and treatment effectiveness. Psychometric testing, assessment of acceptability and whether the use of such scales produces better symptom control, quality of life (QoL), daily function or better prognosis as compared to treatment as usual deserves investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Cannabis use disorder diagnoses are increasing among U.S. adults and are more prevalent among people with comorbid psychiatric disorders. Recent changes in cannabis laws, increasing cannabis availability, and higher-potency cannabis may have placed people with cannabis use and psychiatric disorders at disproportionately increasing risk for cannabis use disorder. The authors used Veterans Health Administration (VHA) data to examine whether trends in cannabis use disorder prevalence among VHA patients differ by whether they have psychiatric disorders., Methods: VHA electronic health records from 2005 to 2019 (N range, 4,332,165-5,657,277) were used to identify overall and age-group-specific (<35, 35-64, and ≥65 years) trends in prevalence of cannabis use disorder diagnoses among patients with depressive, anxiety, posttraumatic stress, bipolar, or psychotic spectrum disorders and to compare these to corresponding trends among patients without any of these disorders. Given transitions in ICD coding, differences in trends were tested within two periods: 2005-2014 (ICD-9-CM) and 2016-2019 (ICD-10-CM)., Results: Greater increases in prevalence of cannabis use disorder diagnoses were observed among patients with psychiatric disorders compared to those without (difference in prevalence change, 2005-2014: 1.91%, 95% CI=1.87-1.96; 2016-2019: 0.34%, 95% CI=0.29-0.38). Disproportionate increases in cannabis use disorder prevalence among patients with psychiatric disorders were greatest among those under age 35 between 2005 and 2014, and among those age 65 or older between 2016 and 2019. Among patients with psychiatric disorders, the greatest increases in cannabis use disorder prevalences were observed among those with bipolar and psychotic spectrum disorders., Conclusions: The findings highlight disproportionately increasing disparities in risk of cannabis use disorder among VHA patients with common psychiatric disorders. Greater public health and clinical efforts are needed to monitor, prevent, and treat cannabis use disorder in this population., Competing Interests: Dr. Saxon receives royalties from UpToDate. Dr. Hasin has received support from Syneos Health.The other authors report no financial relationships with commercial interests.

Background and Aims: International Classification of Diseases (ICD) diagnosis codes are often used in research to identify patients with opioid use disorder (OUD), but their accuracy for this purpose is not fully evaluated. This study describes application of ICD-10 diagnosis codes for opioid use, dependence and abuse from an electronic health record (EHR) data extraction using data from the clinics' OUD patient registries and clinician/staff EHR entries., Design: Cross-sectional observational study., Setting: Four rural primary care clinics in Washington and Idaho, USA., Participants: 307 patients., Measurements: This study used three data sources from each clinic: (1) a limited dataset extracted from the EHR, (2) a clinic-based registry of patients with OUD and (3) the clinician/staff interface of the EHR (e.g. progress notes, problem list). Data source one included records with six commonly applied ICD-10 codes for opioid use, dependence and abuse: F11.10 (opioid abuse, uncomplicated), F11.20 (opioid dependence, uncomplicated), F11.21 (opioid dependence, in remission), F11.23 (opioid dependence with withdrawal), F11.90 (opioid use, unspecified, uncomplicated) and F11.99 (opioid use, unspecified with unspecified opioid-induced disorder). Care coordinators used data sources two and three to categorize each patient identified in data source one: (1) confirmed OUD diagnosis, (2) may have OUD but no confirmed OUD diagnosis, (3) chronic pain with no evidence of OUD and (4) no evidence for OUD or chronic pain., Findings: F11.10, F11.21 and F11.99 were applied most frequently to patients who had clinical diagnoses of OUD (64%, 89% and 79%, respectively). F11.20, F11.23 and F11.90 were applied to patients who had a diagnostic mix of OUD and chronic pain without OUD. The four clinics applied codes inconsistently., Conclusions: Lack of uniform application of ICD diagnosis codes make it challenging to use diagnosis code data from EHR to identify a research population of persons with opioid use disorder., (© 2023 Society for the Study of Addiction.)

Importance: No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder., Objective: To develop an individual-level prediction tool for risk of return to use in opioid use disorder., Design, Setting, and Participants: This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities., Intervention: All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone., Main Outcomes and Measures: Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment., Results: The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84)., Conclusions and Relevance: The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

Purpose: To investigate the prevalence of opioid use disorder (OUD) and medication treatment for OUD (MOUD) receipt in rural primary care settings and identify characteristics associated with MOUD among patients with OUD., Methods: Secondary analyses based on electronic health records of all adult patients who visited 1 of the 6 rural primary care clinic sites from October 2019 to January 2021. Mixed effects logistic regression was conducted to assess MOUD receipt (Y/N) in relation to patient characteristics (eg, demographics, other substance use disorders [SUDs], mental health disorders, and chronic pain) and the number of MOUD prescribers per clinic., Findings: The prevalence of OUD varied from 0.7% to 8.2% (Mean [SD] = 3.3% [95% CI: 0.4, 6.1]) among 36,762 primary care patients across 6 clinic sites. Among 1,164 patients with OUD, on average 50.1% received MOUD (95% CI: 28.0, 72.3). Patients in clinics with more than 3 MOUD prescribers had more than 3 times the odds of receiving MOUD (OR = 3.42; 95% CI, 1.22-9.62) as those in clinics with fewer than 3 prescribers. MOUD was positively associated with younger age (18-30 [OR = 6.97; 95% CI, 3.37-14.42], 31-64 [OR = 5.03; 95% CI, 2.64-9.57], relative to those 65 and older), having other co-occurring SUDs (OR = 3.77; 95% CI, 2.57-5.52), being male (OR = 1.50; 95% CI, 1.12-2.01), and negatively associated with having chronic pain disorders (OR = 0.69; 95% CI, 0.50-0.94)., Conclusions: The prevalence of OUD and MOUD are high but vary considerably across rural primary care clinics; primary care MOUD prescribers play a key role on MOUD access in rural settings., (© 2023 National Rural Health Association.)

Introduction: Opioid overdose deaths are increasing rapidly in the United States. Medications for opioid use disorder (MOUD) are effective and can be delivered in primary care, but uptake has been limited in rural communities. Referral to and coordination with an external telemedicine (TM) vendor by rural primary care clinics for MOUD (TM-MOUD) may increase MOUD access for rural patients, but we know little about perspectives on this model among key stakeholders. As part of a TM-MOUD feasibility study, we explored TM-MOUD acceptability and feasibility among personnel and patients from seven rural primary care clinics and a TM-MOUD vendor., Methods: We conducted virtual interviews or focus groups with clinic administrators (n = 7 interviews), clinic primary care and behavioral health providers (8 groups, n = 30), other clinic staff (9 groups, n = 37), patients receiving MOUD (n = 16 interviews), TM-MOUD vendor staff (n = 4 interviews), and vendor-affiliated behavioral health and prescribing providers (n = 17 interviews). We asked about experiences with and acceptability of MOUD (primarily buprenorphine) and telemedicine (TM) and a TM-MOUD referral and coordination model. We conducted content analysis to identify themes and participants quantitatively rated acceptability of TM-MOUD elements on a 4-item scale., Results: Perceived benefits of vendor-based TM-MOUD included reduced logistical barriers, more privacy and less stigma, and access to services not available locally (e.g., counseling, pain management). Barriers included lack of internet or poor connectivity in patients' homes, limited communication and trust between TM-MOUD and clinic providers, and questions about the value to the clinic of TM-MOUD referral to external vendor. Acceptability ratings for TM-MOUD were generally high; they were lowest among frontline staff., Conclusions: Rural primary care clinic personnel, TM-MOUD vendor personnel, and patients generally perceived referral from primary care to a TM-MOUD vendor to hold potential for increasing access to MOUD in rural communities. Increasing TM-MOUD uptake requires buy-in and understanding among staff of the TM-MOUD workflow, TM services offered, requirements for patients, advantages over clinic-based or TM services from clinic providers, and identification of appropriate patients. Poverty, along with patient hesitation to initiate treatment, creates substantial barriers to MOUD treatment generally; insufficient internet availability creates a substantial barrier to TM-MOUD., Competing Interests: Declaration of competing interest None., (Copyright © 2023 RAND Corporation. Published by Elsevier Inc. All rights reserved.)

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments., Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization., Design, Setting, and Participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after., Intervention: The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine., Main Outcomes and Measures: The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up., Results: During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70)., Conclusions and Relevance: The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD., Trial Registration: ClinicalTrials.gov Identifier: NCT03407638.

Background: Cannabis use disorder is associated with considerable comorbidity and impairment in functioning, and prevalence is increasing among adults with chronic pain. We aimed to assess the effect of introduction of medical cannabis laws (MCL) and recreational cannabis laws (RCL) on the increase in cannabis use disorder among patients in the US Veterans Health Administration (VHA)., Methods: Data from patients with one or more primary care, emergency, or mental health visit to the VHA in 2005-19 were analysed using 15 repeated cross-sectional VHA electronic health record datasets (ie, one dataset per year). Patients in hospice or palliative care were excluded. Patients were stratified as having chronic pain or not using an American Pain Society taxonomy of painful medical conditions. We used staggered-adoption difference-in-difference analyses to estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed cannabis use disorder and associations with presence of chronic pain, accounting for the year that state laws were enacted. We did this by fitting a linear binomial regression model stratified by pain, with time-varying cannabis law status, fixed effects for state, categorical year, time-varying state-level sociodemographic covariates, and patient covariates (age group [18-34 years, 35-64 years, and 65-75 years], sex, and race and ethnicity)., Findings: Between 2005 and 2019, 3 234 382-4 579 994 patients were included per year. Among patients without pain in 2005, 5·1% were female, mean age was 58·3 (SD 12·6) years, and 75·7%, 15·6%, and 3·6% were White, Black, and Hispanic or Latino, respectively. In 2019, 9·3% were female, mean age was 56·7 (SD 15·2) years, and 68·1%, 18·2%, and 6·5% were White, Black, and Hispanic or Latino, respectively. Among patients with pain in 2005, 7·1% were female, mean age was 57·2 (SD 11·4) years, and 74·0%, 17·8%, and 3·9% were White, Black, and Hispanic or Latino, respectively. In 2019, 12·4% were female, mean age was 57·2 (SD 13·8) years, and 65·3%, 21·9%, and 7·0% were White, Black, and Hispanic or Latino, respectively. Among patients with chronic pain, enacting MCL led to a 0·135% (95% CI 0·118-0·153) absolute increase in cannabis use disorder prevalence, with 8·4% of the total increase in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·188% (0·160-0·217) absolute increase in cannabis use disorder prevalence, with 11·5% of the total increase in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in cannabis use disorder prevalence (MCL: 0·037% [0·027-0·048], 5·7% attributable to MCL; RCL: 0·042% [0·023-0·060], 6·0% attributable to RCL). Overall, associations of MCL and RCL with cannabis use disorder were greater in patients with chronic pain than in patients without chronic pain., Interpretation: Increasing cannabis use disorder prevalence among patients with chronic pain following state legalisation is a public health concern, especially among older age groups. Given cannabis commercialisation and widespread public beliefs about its efficacy, clinical monitoring of cannabis use and discussion of the risk of cannabis use disorder among patients with chronic pain is warranted., Funding: NIDA grant R01DA048860, New York State Psychiatric Institute, and the VA Centers of Excellence in Substance Addiction Treatment and Education., Competing Interests: Declaration of interests DSH receives support from Syneos Health for an unrelated project. JLG reports consulting fees from Hoffman-La Roche, a patent pending (use of glecaprevir and pibrentasvir for the treatment of post-traumatic stress disorder), and participation on a data safety monitoring board or advisory board for National Institute of Mental Health (using machine learning to optimise user engagement and clinical response to digital mental health interventions). SSM serves on the Board of Directors for the College on Problems of Drug Dependence. AJS has received consulting fees from Indivior, travel support from Alkermes, research support from MedicaSafe, and royalties from UpTo-Date. KMK has served as an expert witness in litigation. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to examine trends in cannabis-positive urine drug screens (UDSs) among emergency department (ED) patients from 2008 to 2019 using data from the Veterans Health Administration (VHA) health care system, and whether these trends differed by age group (18-34, 35-64, and 65-75 years), sex, and race, and ethnicity., Method: VHA electronic health records from 2008 to 2019 were used to identify the percentage of unique VHA patients seen each year at an ED, received a UDS, and screened positive for cannabis. Trends in cannabis-positive UDS were examined by age, race and ethnicity, and sex within age groups., Results: Of the VHA ED patients with a UDS, the annual prevalence positive for cannabis increased from 16.42% in 2008 to 27.2% in 2019. The largest increases in cannabis-positive UDS were observed in the younger age groups. Male and female ED patients tested positive for cannabis at similar levels. Although the prevalence of cannabis-positive UDS was consistently highest among non-Hispanic Black patients, cannabis-positive UDS increased in all race and ethnicity groups., Discussion: The increasing prevalence of cannabis-positive UDS supports the validity of previously observed population-level increases in cannabis use and cannabis use disorder from survey and administrative records. Time trends via UDS results provide additional support that previously documented increases in self-reported cannabis use and disorder from surveys and claims data are not spuriously due to changes in patient willingness to report use as it becomes more legalized, or due to greater clinical attention over time., (Copyright © 2023 American Society of Addiction Medicine.)

Background: Cocaine use disorder (CUD) is a significant public health issue for which there is no Food and Drug Administration-approved pharmacotherapy. Depressive disorders are common psychiatric comorbidity amongst individuals with CUD., Methods: A retrospective cohort study was conducted among 161,544 patients diagnosed with CUD and depression to evaluate the effectiveness of 13 antidepressants on CUD remission. For any antidepressant found to be associated with CUD remission that had an additional indication, we conducted an additional analysis to evaluate the effectiveness of the candidate drug in patients with CUD with that indication. We then analyzed publicly genomic and functional databases to identify potential explanatory mechanisms of action of the candidate drug in the treatment of CUD., Results: Among these antidepressants, bupropion was associated with higher rates of CUD remission compared to propensity-score matched patients prescribed other antidepressants: hazard ratio (HR) and 95% confidence interval (CI) 1.57 (95% CI: 1.27-1.94). Bupropion is also approved for smoking cessation. We identified CUD patients with co-occurring nicotine dependence and observed that patients prescribed bupropion displayed a higher rate of CUD remission compared to matched individuals prescribed other drugs for nicotine dependence: 1.38 (95% CI: 1.11-1.71). Genetic and functional analyses revealed that bupropion interacts with four protein-encoding genes (COMT, DRD2, SLC6A3, and SLC6A4) which are also associated with CUD and targets CUD-associated pathways including serotonergic synapses, cocaine addiction, and dopaminergic synapses., Conclusions: Our findings suggest that bupropion might be considered a treatment for improving CUD remission in patients with CUD and co-occurring depression or nicotine dependence., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1369.

Objective: Patients in treatment with medications for opioid use disorder (MOUD) often report use of other substances in addition to opioids. Few studies exist that examine the relationship between use at treatment entry and early non-opioid use in opioid treatment outcome., Methodology: We combined and harmonized three randomized, controlled MOUD clinical trials from the National Institutes of Drug Abuse (NIDA) Clinical Trials Network (CTN) (N=2197) and investigated the association of non-opioid substance use at treatment entry and during early treatment with a return to opioid use. The trials compared MOUD treatment (buprenorphine, methadone, extended-release naltrexone) in populations with opioid use disorder (OUD). Non-opioid substances were identified through harmonizing self-reported use. The primary outcomes were markers of return to opioid use by 12 weeks., Results: When treatment cohorts were adjusted, no association between self-reported treatment entry use of non-opioid substances and week-12 opioid use was detected. During the first month of treatment, higher use of cocaine (OR 1.41 [1.18-1.69]) and amphetamine (OR 1.70 [1.27-2.26]) was found to be associated with higher likelihood of illicit opioid use by week 12. Exploratory analyses of potential treatment cohort-by-predictor interactions showed that those with heavier cocaine use had a lower rate of returning to opioid use in the extended-release naltrexone group than in the methadone group., Conclusion: Substance use other than opioids at treatment entry is not associated with relapse. Use of cocaine or amphetamines during the first few weeks of MOUD treatment may signal a worse outcome, suggesting a need for additional interventions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FC: No known competing financial interests or personal relationships, MCH: No known competing financial interests or personal relationships, YL: No known competing financial interests or personal relationships, RRB: No known competing financial interests or personal relationships, RDW: Alkermes, Inc, JR: Alkermes, Indivior, Braeburn, Pear Therapeutics, Chess Health, and Data Cubed, EVN: Alkermes, Indivior, Braeburn, Pear Therapeutics, Chess Health, Brainsway, and Camurus, AJS: Alkermes, Indivior, and UpToDate, DJF: No known competing financial interests or personal relationships, SXL: No known competing financial interests or personal relationships., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose of Review: Veterans are a large population that is disproportionately affected by various physical and mental health conditions. The primary aim of this review is to provide a concise overview of recent literature on the prevalence of cannabis use and cannabis use disorder (CUD) among US Veterans, and associations with mental and physical health conditions. We also addressed gaps in the literature by investigating associations between CUD and mental and physical health conditions in 2019 data from the Veterans Health Administration (VHA; N=5,657,277)., Recent Findings: In total, 25 studies were reviewed. In 2019, the prevalence of Veteran cannabis use ranged from 11.9%-18.7%. Cannabis use and CUD were associated with bipolar disorders, psychotic disorders, suicidality, pain conditions, and other substance use, but less consistently associated with depressive disorders, anxiety disorders, and posttraumatic stress disorder. Analyses of 2019 VHA data indicated that CUD was strongly associated with a broad array of physical and mental health conditions and mortality., Summary: Cannabis use and CUD are prevalent and highly comorbid with other conditions among US Veterans. Harm reduction methods tailored to these populations are needed.

Abstract: In the United States, cannabis is increasingly used to manage chronic pain. Veterans Health Administration (VHA) patients are disproportionately affected by pain and may use cannabis for symptom management. Because cannabis use increases the risk of cannabis use disorders (CUDs), we examined time trends in CUD among VHA patients with and without chronic pain, and whether these trends differed by age. From VHA electronic health records from 2005 to 2019 (∼4.3-5.6 million patients yearly), we extracted diagnoses of CUD and chronic pain conditions ( International Classification of Diseases [ ICD ]- 9-CM , 2005-2014; ICD-10-CM , 2016-2019). Differential trends in CUD prevalence overall and age-stratified (<35, 35-64, or ≥65) were assessed by any chronic pain and number of pain conditions (0, 1, or ≥2). From 2005 to 2014, the prevalence of CUD among patients with any chronic pain increased significantly more (1.11%-2.56%) than those without pain (0.70%-1.26%). Cannabis use disorder prevalence increased significantly more among patients with chronic pain across all age groups and was highest among those with ≥2 pain conditions. From 2016 to 2019, CUD prevalence among patients age ≥65 with chronic pain increased significantly more (0.63%-1.01%) than those without chronic pain (0.28%-0.47%) and was highest among those with ≥2 pain conditions. Over time, CUD prevalence has increased more among VHA patients with chronic pain than other VHA patients, with the highest increase among those age ≥65. Clinicians should monitor symptoms of CUD among VHA patients and others with chronic pain who use cannabis, and consider noncannabis therapies, particularly because the effectiveness of cannabis for chronic pain management remains inconclusive., (Copyright © 2023 International Association for the Study of Pain.)

Purpose: The use of telemedicine (TM) has accelerated in recent years, yet research on the implementation and effectiveness of TM-delivered medication treatment for opioid use disorder (MOUD) has been limited. This study investigated the feasibility of implementing a care coordination model involving MOUD delivered via an external TM provider for the purpose of expanding access to MOUD for patients in rural settings., Methods: The study tested a care coordination model in 6 rural primary care sites by establishing referral and coordination between the clinic and a TM company for MOUD. The intervention spanned approximately 6 months from July/August 2020 to January 2021, coinciding with the peak of the COVID-19 pandemic. Each clinic tracked patients with OUD in a registry during the intervention period. A pre-/post-intervention design (N = 6) was used to assess the clinic-level outcome as patient-days on MOUD based on patient electronic health records., Findings: All clinics implemented critical components of the intervention, with an overall TM referral rate of 11.7% among patients in the registry. Five of the 6 sites showed an increase in patient-days on MOUD during the intervention period compared to the 6-month period before the intervention (mean increase per 1,000 patients: 132 days, P = .08, Cohen's d = 0.55). The largest increases occurred in clinics that lacked MOUD capacity or had a greater number of patients initiating MOUD during the intervention period., Conclusions: To expand access to MOUD in rural settings, the care coordination model is most effective when implemented in clinics that have negligible or limited MOUD capacity., (© 2023 The Authors. The Journal of Rural Health published by Wiley Periodicals LLC on behalf of National Rural Health Association.)

Introduction: The Brief Addiction Monitor-Revised (BAM-R) is a widely used, 17-item assessment of substance use, risk, and protective factors associated with recovery from substance use disorders. Despite wide adoption in the U.S. Department of Veterans Affairs (VA) and recommendations for use in measurement-based care (MBC), administration may not be feasible in many MBC settings due to time constraints. The purpose of this study was to derive a shortened version of the BAM-R for use in fast-paced healthcare settings., Methods: BAM-R data from 32,002 Veterans were obtained through the VA's Corporate Data Warehouse. We used logistic regression models to identify items for removal based on prediction of two clinical outcomes (90-day substance use disorder (SUD) treatment retention and 12-month mortality) and item-level sensitivity to change during substance use treatment., Results: Although no intake BAM-R items predicted SUD treatment retention or mortality, effect sizes for item-level sensitivity to change during substance use treatment varied from small to large. Seven items were judged as relevant for MBC of SUD. Among all BAM-R items, Heavy Alcohol Use, Self-Help, Drug Use, Craving, and Mood items demonstrated the greatest magnitude of sensitivity to change., Conclusions: Although additional research is recommended before a shortened BAM-R can be implemented in non-specialty MBC settings, we identified 5 BAM-R items with perceived clinical utility and scores that demonstrated evidence of sensitivity to change. Shortening the BAM-R increases feasibility of use, though more work is needed to optimize measurement for SUD MBC., Competing Interests: None of the authors have any conflicts of interest to report. The views expressed in this article are those of these authors only and do not reflect the position or policies of any of the affiliated agencies., (© 2023 The Authors. Published by Elsevier B.V.)

Introduction: Although methamphetamine use is rising in the United States, its impacts on patient outcomes among persons undergoing treatment for opioid use disorder (OUD) remain unclear. This study aims to assess the association between baseline methamphetamine/amphetamine (MA/A) use and subsequent illicit opioid use among patients with OUD initiating buprenorphine in an office-based setting., Methods: We conducted a secondary analysis of a pilot randomized controlled trial of a behavioral mobile health intervention for buprenorphine adherence conducted over a 12-week study period at two clinic sites. The study defined baseline MA/A use by a positive urine drug test (UDT) and/or self-report of use within the past 30-days. Separate Poisson regression models with robust standard errors evaluated associations between MA/A and: i) illicit opioid use measured by weekly UDT (primary) and ii) self-reported past 30-day use at end of study (secondary). Other secondary outcomes included buprenorphine positive UDTs throughout the study and retention in OUD treatment at both weeks 12 and 24 post-randomization., Results: At baseline, 28 (36%) of the 78 participants had MA/A use and use was associated with a statistically significant increase in risk of testing positive for illicit opioids on UDT during the study follow-up period (adjusted relative risk (aRR)=1.54; 95% CI=1.09-2.17; p=0.015), as well as an increased risk for reported past 30-day illicit opioid use at week 12 (aRR=3.86; 95% CI=1.47-10.18; P=0.006). The study found no significant associations between MA/A use and buprenorphine positive UDT or retention in OUD treatment., Conclusions: In this sample of patients initiating buprenorphine, methamphetamine/amphetamine use at baseline was associated with illicit opioid use over a 12-week period. These findings demonstrate how co-use of methamphetamine can impede attainment of ideal OUD treatment outcomes., Competing Interests: Competing Interests: None

Importance: Medication for opioid use disorder (MOUD) (eg, buprenorphine and naltrexone) can be offered in primary care, but barriers to implementation exist., Objective: To evaluate an implementation intervention over 2 years to explore experiences and perspectives of multidisciplinary primary care (PC) teams initiating or expanding MOUD., Design, Setting, and Participants: This survey-based and ethnographic qualitative study was conducted at 12 geographically and structurally diverse primary care clinics that enrolled in a hybrid effectiveness-implementation study from July 2020 to July 2022 and included PC teams (prescribing clinicians, nonprescribing behavioral health care managers, and consulting psychiatrists). Survey data analysis was conducted from February to April 2022., Exposure: Implementation intervention (external practice facilitation) to integrate OUD treatment alongside existing collaborative care for mental health services., Measures: Data included (1) quantitative surveys of primary care teams that were analyzed descriptively and triangulated with qualitative results and (2) qualitative field notes from ethnographic observation of clinic implementation meetings analyzed using rapid assessment methods., Results: Sixty-two primary care team members completed the survey (41 female individuals [66%]; 1 [2%] American Indian or Alaskan Native, 4 [7%] Asian, 5 [8%] Black or African American, 5 [8%] Hispanic or Latino, 1 [2%] Native Hawaiian or Other Pacific Islander, and 46 [4%] White individuals), of whom 37 (60%) were between age 25 and 44 years. An analysis of implementation meetings (n = 362) and survey data identified 4 themes describing multilevel factors associated with PC team provision of MOUD during implementation, with variation in their experience across clinics. Themes characterized challenges with clinical administrative logistics that limited the capacity to provide rapid access to care and patient engagement as well as clinician confidence to discuss aspects of MOUD care with patients. These challenges were associated with conflicting attitudes among PC teams toward expanding MOUD care., Conclusions and Relevance: The results of this survey and qualitative study of PC team perspectives suggest that PC teams need flexibility in appointment scheduling and the capacity to effectively engage patients with OUD as well as ongoing training to maintain clinician confidence in the face of evolving opioid-related clinical issues. Future work should address structural challenges associated with workload burden and limited schedule flexibility that hinder MOUD expansion in PC settings.

Background: Methadone, a cornerstone of opioid use disorder treatments for many decades, is an essential tool for combatting the opioid epidemic. However, requirements for observing methadone dosing in person through direct observed therapy (DOT) impose significant barriers for many patients. Digital technology can facilitate remote DOT, which could reduce barriers to methadone treatment. Currently, there are limited data on the usability of such technology among patients and counselors in methadone treatment settings., Objective: The primary objective of this study was to assess the workload, usability, and engagement of a video-based DOT mobile app for patients with opioid use disorder receiving methadone treatment. The secondary objective was to assess the workload, usability, and engagement of the provider-facing app portal used by counselors., Methods: Patients (n=12) and counselors (n=3) who previously tried video DOT for methadone through a smartphone app in an opioid treatment program participated in usability testing sessions. Participants completed essential tasks for video DOT, then provided ratings of workload (NASA Task Load Index), usability (modified System Usability Scale), and engagement (modified Engagement Scale) with the core features of the video DOT program., Results: Patients and counselors reported low mental, physical, and temporal demands, successful performance, low effort, and low frustration associated with activities. Patients reported high usability (mean 85, SD 9.5) and engagement (mean 3.8, SD 1.1); counselors reported moderate usability (mean 43.3, SD 17.7) and engagement (mean 2.81, SD 0.63)., Conclusions: A mobile health app that facilitates video-based DOT for methadone required a low workload for patients and counselors and was highly usable for patients in an opioid treatment program; however, there are opportunities to improve usability and engagement for the counselor-facing portal., (©Bulat Idrisov, Kevin A Hallgren, Alyssa Michaels, Sean Soth, James Darnton, Paul Grekin, Steve Woolworth, Andrew J Saxon, Judith I Tsui. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 13.07.2023.)

Background: In the United States, methamphetamine-related overdoses have tripled from 2015 to 2020 and continue to rise. However, efficacious treatments such as contingency management (CM) are often unavailable in health systems., Objective: We conducted a single-arm pilot study to evaluate the feasibility, engagement, and usability of a fully remotely delivered mobile health CM program offered to adult outpatients who used methamphetamine and were receiving health care within a large university health system., Methods: Participants were referred by primary care or behavioral health clinicians between September 2021 and July 2022. Eligibility criteria screening was conducted by telephone and included self-reported methamphetamine use on ≥5 out of the past 30 days and a goal of reducing or abstaining from methamphetamine use. Eligible participants who agreed to take part then completed an initial welcome phase that included 2 videoconference calls to register for and learn about the CM program and 2 "practice" saliva-based substance tests prompted by a smartphone app. Participants who completed these welcome phase activities could then receive the remotely delivered CM intervention for 12 consecutive weeks. The intervention included approximately 24 randomly scheduled smartphone alerts requesting a video recording of themselves taking a saliva-based substance test to verify recent methamphetamine abstinence, 12 weekly calls with a CM guide, 35 self-paced cognitive behavioral therapy modules, and multiple surveys. Financial incentives were disbursed via reloadable debit cards. An intervention usability questionnaire was completed at the midpoint., Results: Overall, 37 patients completed telephone screenings, with 28 (76%) meeting the eligibility criteria and consenting to participate. Most participants who completed a baseline questionnaire (21/24, 88%) self-reported symptoms consistent with severe methamphetamine use disorder, and most had other co-occurring non-methamphetamine substance use disorders (22/28, 79%) and co-occurring mental health disorders (25/28, 89%) according to existing electronic health records. Overall, 54% (15/28) of participants successfully completed the welcome phase and were able to receive the CM intervention. Among these participants, engagement with substance testing, calls with CM guides, and cognitive behavioral therapy modules varied. Rates of verified methamphetamine abstinence in substance testing were generally low but varied considerably across participants. Participants reported positive opinions about the intervention's ease of use and satisfaction with the intervention., Conclusions: Fully remote CM can be feasibly delivered within health care settings lacking existing CM programs. Although remote delivery may help reduce barriers to treatment access, many patients who use methamphetamine may struggle to engage with initial onboarding. High rates of co-occurring psychiatric conditions in the patient population may also contribute to uptake and engagement challenges. Future efforts could leverage greater human-to-human connection, more streamlined onboarding procedures, larger incentives, longer durations, and the incentivization of non-abstinence-based recovery goals to increase uptake and engagement with fully remote mobile health-based CM., (©Kevin A Hallgren, Mark H Duncan, Matthew D Iles-Shih, Eliza B Cohn, Connor J McCabe, Yanni M Chang, Andrew J Saxon. Originally published in JMIR Formative Research (https://formative.jmir.org), 06.07.2023.)