Identification and biophysical characterization of a novel domain-swapped camelid antibody specific for fentanyl.

Opioid use disorders (OUD) and overdoses are ever-evolving public health threats that continue to grow in incidence and prevalence in the United States and abroad. Current treatments consist of opioid receptor agonists and antagonists, which are safe and effective but still suffer from some limitations. Murine and humanized monoclonal antibodies (mAb) have emerged as an alternative and complementary strategy to reverse and prevent opioid-induced respiratory depression. To explore antibody applications beyond traditional heavy-light chain mAbs, we identified and biophysically characterized a novel single-domain antibody specific for fentanyl from a camelid variable-heavy-heavy (VHH) domain phage display library. Structural data suggested that VHH binding to fentanyl was facilitated by a unique domain-swapped dimerization mechanism, which accompanied a rearrangement of complementarity-determining region loops leading to the formation of a fentanyl-binding pocket. Structure-guided mutagenesis further identified an amino acid substitution that improved the affinity and relaxed the requirement for dimerization of the VHH in fentanyl binding. Our studies demonstrate VHH engagement of an opioid and inform on how to further engineer a VHH for enhanced stability and efficacy, laying the groundwork for exploring the in vivo applications of VHH-based biologics against OUD and overdose.

Glial modulators as novel therapeutics for comorbid pain and opioid use disorder.

Chronic pain and opioid use disorder (OUD) are major public health problems, with rising opioid-related overdose deaths linked to increased opioid prescriptions for pain management. Novel treatment approaches for these commonly comorbid disorders are needed. Growing evidence supports a role for glial activation for both chronic pain and substance use disorders, including OUD. This review provides an overview of glial modulators as a novel treatment approach for comorbid pain and OUD. We aim to synthesize clinical studies investigating the efficacy of glial modulators in treating these comorbid disorders. We conducted a literature search of PubMed and Google Scholar databases in October 2023 to identify relevant clinical trials. The included studies varied in terms of patient population, study methodology and outcomes assessed, and were often limited by small sample sizes and other methodological issues. Additionally, several glial modulators have yet to be studied for chronic pain and OUD. Despite these limitations, these studies yielded positive signals that merit further investigation. Both chronic pain and OUD remain significant public health problems, with many treatment challenges. Glial modulators continue to hold promise as novel therapeutics for comorbid pain and OUD, given positive indications that they can improve pain measures, and reduce addiction-related outcomes. As our understanding of the mechanisms underlying the contributions of glial modulators to pain and addiction behaviours deepens, we will be better equipped to identify more specific therapeutic targets for chronic pain and OUD.

From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder.

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.

Does cannabis use substitute for opioids? A preliminary exploratory survey in opioid maintenance patients.

Various studies showed that people with substance use disorder use cannabis to reduce withdrawal or dose of their main drug. Using a questionnaire about their cannabis use, 118 participants in an opioid maintenance treatment (OMT) in Germany were examined regarding this strategy. 60% reported to use cannabis. Of those, 72% were using cannabis in the suggested way. Cannabis was used to substitute for, e.g., heroin (44.8%) and benzodiazepines (16.4%). We also asked for an estimation of how good cannabis was able to substitute for several substances (in German school grades (1 till 6)); heroin average grade: 2.6 ± 1.49. Besides that we asked about the idea of cannabis as "self-medication", e.g., to reduce pain (47%) and about negative consequences from cannabis use. Our results suggest to consider the use of cannabis by patients in OMT rather as a harm reduction strategy to reduce the intake of more dangerous drugs.

Withdrawal catastrophizing scale: initial psychometric properties and implications for the study of opioid use disorder and hyperkatifeia.

Background: Discovery of modifiable factors influencing subjective withdrawal experience might advance opioid use disorder (OUD) research and precision treatment. This study explores one factor - withdrawal catastrophizing - a negative cognitive and emotional orientation toward withdrawal characterized by excessive fear, worry or inability to divert attention from withdrawal symptoms.Objectives: We define a novel concept - withdrawal catastrophizing - and present an initial evaluation of the Withdrawal Catastrophizing Scale (WCS).Methods: Prospective observational study (n = 122, 48.7% women). Factor structure (exploratory factor analysis) and internal consistency (Cronbach's α) were assessed. Predictive validity was tested via correlation between WCS and next-day subjective opiate withdrawal scale (SOWS) severity. The clinical salience of WCS was evaluated by correlation between WCS and withdrawal-motivated behaviors including risk taking, OUD maintenance, OUD treatment delay, history of leaving the hospital against medical advice and buprenorphine-precipitated withdrawal.Results: WCS was found to have a two-factor structure (distortion and despair), strong internal consistency (α = .901), and predictive validity - Greater withdrawal catastrophizing was associated with next-day SOWS (rs (99) = 0.237, p = .017). Withdrawal catastrophizing was also correlated with risk-taking behavior to relieve withdrawal (rs (119) = 0.357, p < .001); withdrawal-motivated OUD treatment avoidance (rs (119) = 0.421, p < .001), history of leaving the hospital against medical advice (rs (119) = 0.373, p < .001) and buprenorphine-precipitated withdrawal (rs (119) = 0.369, p < .001).Conclusion: This study provides first evidence of withdrawal catastrophizing as a clinically important phenomenon with implications for the future study and treatment of OUD.

Withdrawal interference scale: a novel measure of withdrawal-related life disruption in opioid use disorder and alcohol use disorder.

Background: Hyperkatifeia describes amplified emotional and motivational withdrawal due to addiction-related sensitization of brain-stress-systems. Hyperkatifeia has been proposed as a target for addiction treatment development. However, translation of basic research in this area will require new tools designed to measure hyperkatifeia and related phenomena outside of laboratory settings.Objectives: We define a novel concept, withdrawal interference, and introduce a new tool - the Withdrawal Interference Scale (WIS) - which measures the impact of withdrawal on daily life among individuals with OUD or AUD.Methods: Described are the combined results of three separate cross-sectional studies. The structural validity, convergent validity, construct validity, trans-diagnostic (AUD/OUD) configural, metric, and scalar invariance, internal consistency, and composite reliability of WIS was tested among three independent samples of 1) treatment-seeking adults with OUD (n = 132), 2) treatment-seeking adults with AUD (n = 123), and 3) non-treatment-seeking adults with OUD (n = 140). Males numbered 218 and females were 163.Results: WIS exhibited structural validity (1 factor), convergent validity (average variance extracted .670-.676), construct validity, trans-diagnostic configural (χ2/df = 2.10), metric (Δχ2 = 5.70, p = .681), and scalar invariance (Δχ2 = 12.34, p = .338), internal consistency (α .882-928), and composite reliability (.924-.925).Conclusion: These results suggest WIS is a valid and reliable instrument for measuring withdrawal-related life disruption in AUD and OUD. Further, given our findings of transdiagnostic measurement invariance, WIS scores of individuals with AUD and OUD can be meaningfully compared in future statistical analyses.

The Perceived Role of Withdrawal in Maintaining Opioid Addiction among Adults with Untreated Opioid Use Disorder: A Survey of Syringe Exchange Program Participants.

Background: Withdrawal is believed to play a central role in the brain disease model of addiction. However, little research describes withdrawal-motives among untreated individuals in community settings. Methods: This cross-sectional study surveyed syringe exchange program participants (n = 139) with untreated opioid use disorder (OUD) in Columbus, Ohio from January 10th to March 25th, 2023, to assess their perceptions of the role of withdrawal in OUD maintenance, treatment delay, and OUD's refractoriness to buprenorphine. Participants responded to a survey including DSM-5 OUD criteria, demographics, and questions about substance use and opioid withdrawal. Participant ages ranged from 21 to 65 years with a mean age of 37.5 years and standard deviation of 8.1. The racial distribution of the sample was as follows: 81% White/Caucasian, 12% Black/African American, 3% Native American or Alaskan Native. Results: Sixty-six percent of participants agreed, or strongly agreed that opioid withdrawal was "the most important reason" they had been unable to stop using opioids. Almost seventy-one percent agreed, or strongly agreed that worry about opioid withdrawal had caused them to "put off or delay" OUD treatment. Although all participants had active, untreated OUD at the time of recruitment, most (85%) had previously tried buprenorphine, and the majority (78%) reported having experienced buprenorphine-precipitated withdrawal. Conclusions: Among this community sample of individuals with untreated OUD, withdrawal was perceived to have an important role in maintaining OUD, including by motivating OUD treatment delay. Prior buprenorphine-precipitated withdrawal was common, suggesting aversion to withdrawal might possibly be associated with OUD's refractoriness to buprenorphine.

Psychotherapies in opioid use disorder: toward a step-care model.

Opioid use disorder (OUD) is characterized by a lack of control in opioid use, resulting in psychological distress and deficits in interpersonal and social functioning. OUD is often associated with psychiatric comorbidities that increase the severity of the disorder. The consequences of OUD are dramatic in terms of increased morbi-mortality. Specific medications and psychotherapies are essential tools not only in the treatment of OUD but also in the prevention of suicide and overdoses. In our review, we assess the different types of psychotherapies (counseling, motivational interviewing, contingency management, cognitive-behavioral therapy, and dialectical-behavior therapy) that are delivered to opioid users, either associated or un-associated with OUD medications and/or medications for psychiatric disabilities. We describe the application of these therapies first to adult opioid users and then to adolescents. This work led us to propose a stepped-care model of psychotherapies for OUD which provided information to assist clinicians in decision-making regarding the selection of psychotherapeutic strategies according to patients' OUD severity.

Impact of Stigma on Clinician Training for Opioid Use Disorder Care: A Qualitative Study in a Primary Care Learning Collaborative.

PURPOSE: We undertook a study to examine how stigma influences the uptake of training on medication for opioid use disorder (MOUD) in primary care academic programs. METHODS: We conducted a qualitative study of 23 key stakeholders responsible for implementing MOUD training in their academic primary care training programs that were participants in a learning collaborative in 2018. We assessed barriers to and facilitators of successful program implementation and used an integrated approach to develop a codebook and analyze the data. RESULTS: Participants represented the family medicine, internal medicine, and physician assistant fields, and they included trainees. Most participants described clinician and institutional attitudes, misperceptions, and biases that enabled or hindered MOUD training. Perceptions included concerns that patients with OUD are "manipulative" or "drug seeking." Elements of stigma in the origin domain (ie, beliefs by primary care clinicians or the community that OUD is a choice and not a disease), the enacted domain (eg, hospital bylaws banning MOUD and clinicians declining to obtain an X-Waiver to prescribe MOUD), and the intersectional domain (eg, inadequate attention to patient needs) were perceived as major barriers to MOUD training by most respondents. Participants described strategies that improved the uptake of training, including giving attention to clinician concerns, clarifying the biology of OUD, and ameliorating clinician fears of being ill equipped to provide care for patients. CONCLUSIONS: OUD-related stigma was commonly reported in training programs and impeded the uptake of MOUD training. Potential strategies to address stigma in the training context, beyond providing content on effective evidence-based treatments, include addressing the concerns of primary care clinicians and incorporating the chronic care framework into OUD treatment.

Oral oxycodone self-administration leads to features of opioid misuse in male and female mice.

Use of prescription opioids, particularly oxycodone, is an initiating factor driving the current opioid epidemic. There are several challenges with modelling oxycodone abuse. First, prescription opioids including oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl, which have been more commonly used in rodent research. This oral route of administration determines the pharmacokinetic profile, which then influences the establishment of drug-reinforcement associations in animals. Moreover, the pattern of intake and the environment in which addictive drugs are self-administered are critical determinants of the levels of drug intake, of behavioural sensitization and of propensity to relapse behaviour. These are all important considerations when modelling prescription opioid use, which is characterized by continuous drug access in familiar environments. Thus, to model features of prescription opioid use and the transition to abuse, we designed an oral, homecage-based oxycodone self-administration paradigm. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and the majority exhibit preference for oxycodone, escalation of intake, physical signs of dependence and reinstatement of seeking after withdrawal. In addition, a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model is therefore translationally relevant and useful for studying the neurobiological substrates of prescription opioid abuse.

Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study.

The opioid and cannabinoid receptor systems are inextricably linked-overlapping at the anatomical, functional and behavioural levels. Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD). We conducted an experimental study to investigate the acute effects of the delta-9-tetrahydrocannabinol (THC) among persons receiving methadone therapy for OUD. Using a within-subject, crossover, human laboratory design, 25 persons on methadone therapy for OUD (24% women) were randomly assigned to receive single oral doses of THC (10 or 20 mg, administered as dronabinol) or placebo, during three separate 5-h test sessions. Measures of experimental and self-reported pain sensitivity, abuse potential, cognitive performance and physiological effects were collected. Mixed-effects models examined the main effects of THC dose and interactions between THC (10 and 20 mg) and methadone doses (low-dose methadone defined as <90 mg/day; high dose defined as >90 mg/day). Results demonstrated that, for self-reported rather than experimental pain sensitivity measures, 10 mg THC provided greater relief than 20 mg THC, with no substantial evidence of abuse potential, and inconsistent dose-dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses. Collectively, these results provide valuable insights for future studies aiming to evaluate the risk-benefit profile of cannabinoids to relieve pain among individuals receiving opioid agonist therapy for OUD, a timely endeavour amidst the opioid crisis.

Baseline characteristics of people experiencing homelessness with a recent drug overdose in the PHOENIx pilot randomised controlled trial.

BACKGROUND: Drug-related deaths in Scotland are the highest in Europe. Half of all deaths in people experiencing homelessness are drug related, yet we know little about the unmet health needs of people experiencing homelessness with recent non-fatal overdose, limiting a tailored practice and policy response to a public health crisis. METHODS: People experiencing homelessness with at least one non-fatal street drug overdose in the previous 6 months were recruited from 20 venues in Glasgow, Scotland, and randomised into PHOENIx plus usual care, or usual care. PHOENIx is a collaborative assertive outreach intervention by independent prescriber NHS Pharmacists and third sector homelessness workers, offering repeated integrated, holistic physical, mental and addictions health and social care support including prescribing. We describe comprehensive baseline characteristics of randomised participants. RESULTS: One hundred and twenty-eight participants had a mean age of 42 years (SD 8.4); 71% male, homelessness for a median of 24 years (IQR 12-30). One hundred and eighteen (92%) lived in large, congregate city centre temporary accommodation. A quarter (25%) were not registered with a General Practitioner. Participants had overdosed a mean of 3.2 (SD 3.2) times in the preceding 6 months, using a median of 3 (IQR 2-4) non-prescription drugs concurrently: 112 (87.5%) street valium (benzodiazepine-type new psychoactive substances); 77 (60%) heroin; and 76 (59%) cocaine. Half (50%) were injecting, 50% into their groins. 90% were receiving care from Alcohol and Drug Recovery Services (ADRS), and in addition to using street drugs, 90% received opioid substitution therapy (OST), 10% diazepam for street valium use and one participant received heroin-assisted treatment. Participants had a mean of 2.2 (SD 1.3) mental health problems and 5.4 (SD 2.5) physical health problems; 50% received treatment for physical or mental health problems. Ninety-one per cent had at least one mental health problem; 66% had no specialist mental health support. Participants were frail (70%) or pre-frail (28%), with maximal levels of psychological distress, 44% received one or no daily meal, and 58% had previously attempted suicide. CONCLUSIONS: People at high risk of drug-related death continue to overdose repeatedly despite receiving OST. High levels of frailty, multimorbidity, unsuitable accommodation and unmet mental and physical health care needs require a reorientation of services informed by evidence of effectiveness and cost-effectiveness. Trial registration UK Clinical Trials Registry identifier: ISRCTN 10585019.

Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use.

Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal-striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.

Interleukin-1 receptor-associated kinase 4 (IRAK4) in the nucleus accumbens regulates opioid-seeking behavior in male rats.

Opioid addiction remains a severe health problem. While substantial insights underlying opioid addiction have been yielded from neuron-centric studies, the contribution of non-neuronal mechanisms to opioid-related behavioral adaptations has begun to be recognized. Toll-like receptor 4 (TLR4), a pattern recognition receptor, has been widely suggested in opioid-related behaviors. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a kinase essential for TLR4 responses, However, the potential role of IRAK4 in opioid-related responses has not been examined. Here, we explored the role of IRAK4 in cue-induced opioid-seeking behavior in male rats. We found that morphine self-administration increased the phosphorylation level of IRAK4 in the nucleus accumbens (NAc) in rats; the IRAK4 signaling remained activated after morphine extinction and cue-induced reinstatement test. Both systemic and local inhibition of IRAK4 in the NAc core attenuated cue-induced morphine-seeking behavior without affecting the locomotor activity and cue-induced sucrose-seeking. In addition, inhibition of IRAK4 also reduced the cue-induced reinstatement of fentanyl-seeking. Our findings suggest an important role of IRAK4 in opioid relapse-like behaviors and provide novel evidence in the association between innate immunity and drug addiction.

Effects of Substance Use, Recovery, and Non-Drug-Related Online Community Participation on the Risk of a Use Episode During Remission From Opioid Use Disorder: Longitudinal Observational Study.

BACKGROUND: Opioid addiction is currently one of the most pressing public health issues. Despite several treatment options for opioid addiction, the recurrence of use episodes during remission remains high. Research indicates that meaningful membership in various social groups underpins the successful transition from addiction to long-term remission. However, much of the current literature focuses on online peer-support groups for individuals in remission from substance use, sometimes also called recovery groups, a term we will use in line with the terminology used by the online community we studied. In contrast, online group memberships that promote substance use and groups that are unrelated to substance use and remission (non-drug-related groups) are rarely studied. OBJECTIVE: This study aims to understand whether engagement with a variety of Reddit subforums (subreddits) provides those in remission from opioid use disorder (OUD) with social capital, thereby reducing their risk of a use episode over several years. More specifically, it aims to examine the different effects of engagement with substance use, recovery, and non-drug-related subreddits. METHODS: A data set of 457 individuals in remission from OUD who posted their remission start date on Reddit was collected, of whom 219 (47.9%) indicated at least one use episode during the remission period. Using a Cox proportional hazards model, the effects of the number of non-drug-related, recovery, and substance use subreddits an individual had engaged with on the risk of a use episode were tested. Group engagement was assessed both in terms of the absolute number of subreddits and as a proportion of the total number of subreddits in which an individual had posted. RESULTS: Engagement with a larger number of non-drug-related online communities reduced the likelihood of a use episode irrespective of the number of posts and comments made in these forums. This was true for both the absolute number of non-drug-related communities (P<.001) and the proportion of communities with which a person engaged (P<.001). The findings were less conclusive for recovery support and substance use groups; although participating in more recovery support subreddits reduced the risk of a use episode (P<.001), being part of a higher proportion of recovery support groups relative to other subreddits increased the risk (P=.01). A higher proportion of substance use subreddits marginally increased the risk of a use episode (P=.06); however, the absolute number of substance use subreddits significantly reduced the risk of a use episode (P=.002). CONCLUSIONS: Our work indicates that even minimal regular engagement with several non-drug-related online forums may provide those in remission from OUD with an opportunity to grow their social capital and reduce the risk of a use episode over several years.

Hyperbaric Oxygen Therapy for Pain, Opioid Withdrawal, and Related Symptoms: A Pilot Randomized Controlled Trial.

BACKGROUND: Pain, drug cravings, and opioid withdrawal symptoms can interfere with substance use disorder or opioid tapering treatment goals. AIM: This pilot study investigated the feasibility of a protocol designed to test opioid withdrawal symptom relief relative to a sham condition after two consecutive days of hyperbaric oxygen therapy (HBOT) for adults prescribed daily methadone for opioid use disorder. METHOD: Using a double-blind protocol, eight adults were randomized to receive either a full 90-minute HBOT dose in a pressurized chamber with 100% oxygen at 2.0 atmospheres absolute (ATA) or a sham condition receiving 21% oxygen (equivalent to room air within the chamber) at a minimal pressure of ≤1.3 ATA. Measures included study retention, treatment satisfaction, and pre- and post-intervention effects for opioid withdrawal symptoms, drug cravings, pain intensity and interference, sleep quality, and mood. RESULTS: Study retention and treatment satisfaction was high. All measurements improved more, on average, for participants receiving full-dose HBOT treatment than among participants receiving sham treatments except for clinically observed withdrawal symptoms. The largest positive effects were observed in measurements of pain intensity and drug craving. CONCLUSIONS: These pilot results provide evidence to support a fully powered study of HBOT as a potential treatment adjunct for adults receiving methadone for opioid use disorder. Trends towards symptom improvements were detected from pre- to post-HBOT in the full treatment arm versus sham condition. More research into novel non-pharmacologic options to relieve distressing symptoms related to pain and opioid use disorder is essential to improve clinical outcomes.

Comparing Perceptions of Addiction Treatment between Professionals and Individuals in Recovery.

Background: The purpose of this qualitative study was to compare and contrast the differing perspectives of service users and professionals regarding the current substance use disorders (SUD) services provided in Summit County, Ohio. Seven focus groups were conducted with 44 participants (52.3% male, mean age 46 years), including 15 individuals in recovery, 16 direct service providers, and 13 executive directors. The participants were asked about three areas: (1) effective treatment for SUD, (2) challenges for persons with SUD, and (3) suggestions for improving SUD treatment outcomes. The data were analyzed and coded according to major themes. Results: While there were numerous emergent themes that were concordant between service use and professionals, several differing themes between the groups were also identified. First, participants disagreed on the effectiveness of medication-assisted treatment/Medications for Opioid Use Disorder. Second, professionals identified trauma, stigma, "one-size-fits-all" approach to treatment, and limitations set by managed care act as barriers to treatment, whereas individuals in recovery reported difficulty dealing with feelings, feeling of being rushed into recovery, and the lack of long-term recovery plans as the most significant barriers. Lastly, in order to improve treatment outcomes, professionals emphasized the importance of education unlike individuals in recovery who identified sober supports as the most important factor. Conclusion: This study identified challenges in SUD recovery and highlights essential areas for consideration when developing and implementing SUD treatment. The findings can be used as guidelines to provide better services to individuals with SUDs.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2022.2058706 .

A national survey of barriers and facilitators to medications for opioid use disorder among legal-involved veterans in the Veterans Health Administration.

Background: Medications for opioid use disorder (MOUD) are clinically effective at treating OUD among legal-involved populations. However, research shows that legal-involved veterans who receive care through the VHA have lower rates of MOUD use compared to non-legal-involved veterans. Education may be a key factor in intervention strategies to improve MOUD access. This study was a national survey of VHA staff to identify barriers to and facilitators of MOUD, as well as MOUD-related education needs for VHA staff, community partners, criminal justice partners, and legal-involved veterans. Method: A 98-item online survey was conducted to examine VHA staff perspectives (N = 218) around needed education, barriers to, and facilitators of MOUD for legal-involved veterans. Descriptive statistics were conducted and linear regression analyses were used to evaluate differences in perceptions by respondents' current position at the VHA and their VHA facility's rate of provision of MOUD among legal-involved veterans. Results: Respondents endorsed a need for education in all areas of MOUD (e.g., existing medications for the treatment of OUD) for VHA staff and providers, community partners, criminal justice partners, and legal-involved veterans. VHA staff perceived barriers to MOUD for legal-involved veterans to include stigma and complicated guidelines around MOUD and OUD treatment. Facilities with low rates of MOUD use highlighted barriers including MOUD conflicting with the philosophy of the local VHA facility and provider stigma toward patients with OUD. Perceptions of efficacy of MOUD differed by respondents' current position at the VHA such that substance use disorder treatment providers perceived buprenorphine and methadone as more effective compared to Veterans Justice Specialists. Conclusion: The results of this study suggest a need for an educational intervention emphasizing the evidence supporting use of MOUD as a lack of knowledge about these medications was considered a barrier to access, whereas gaining education about MOUD was a facilitator to access. Education strategies specifically tailored to address VHA facility-level differences may help address barriers to MOUD experienced by legal-involved veterans.

Risk factors associated with recent opioid-related hospitalizations in children: a nationwide analysis.

PURPOSE: Identifying at-risk children can provide a crucial opportunity for preventative measures to avoid opioid addiction. This study sought to determine at-risk pediatric patients that were previously hospitalized due to other causes prior to their opioid-related admission. METHODS: The Nationwide Readmissions Database (2010-2014) was queried for children 1-18 years old with an opioid-related hospitalization. Previous admissions (up to 1 year prior) and associated diagnoses were compared. Results were weighted for national estimates. RESULTS: 51,349 opioid-related hospitalizations were identified with an overall in-hospital mortality of 0.8%. Seventeen percent had a previous admission during the same calendar year of which 44% had > 1 and 11% had ≥ 5 prior admissions. Only 4% of prior admissions occurred at a different hospital. Males and females were equally represented, and 82% were ≥ 13 years old. Only 16% of previously admitted patients underwent a major surgical procedure during a previous hospitalization. The most common concomitant diagnoses for patients with prior hospitalizations were drug abuse (37%), chronic pulmonary disease (18%), and depression (10%). CONCLUSION: Opioid-related hospitalizations often occur among children with multiple recent admissions, usually to the same hospital. Most patients do not have a history of cancer or recent surgery to account for their opioid use.

Impaired working memory performance in opioid-dependent patients is related to reduced insula gray matter volume: a voxel-based morphometric study.

Opioid-dependent patients frequently show deficits in multiple cognitive domains that might impact on their everyday life performance and interfere with therapeutic efforts. To date, the neurobiological underpinnings of those deficits remain to be determined. We investigated working memory performance and gray matter volume (GMV) differences in 17 patients on opioid maintenance treatment (OMT) and 17 healthy individuals using magnetic resonance imaging and voxel-based morphometry. In addition, we explored associations between substance intake, gray matter volume, and working memory task performance. Patients on OMT committed more errors during the working memory task than healthy individuals and showed smaller insula and putamen GMV. The duration of heroin use prior to OMT was associated with working memory performance and insula GMV in patients. Neither the substitution agent (methadone and buprenorphine) nor concurrent abuse of illegal substances during the 3 months prior to the experiment was significantly associated with GMV. Results indicate that impaired working memory performance and structural deficits in the insula of opioid-dependent patients are related to the duration of heroin use. This suggests that early inclusion into OMT or abstinence-oriented therapies that shorten the period of heroin abuse may limit the impairments to GMV and cognitive performance of opioid-dependent individuals.