Functional Domains of Substance Use and their Implications to Trauma: A Systematic Review of Neuroimaging Studies.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

Narrative review: Revised Principles and Practice Recommendations for Adolescent Substance Use Treatment and Policy.

OBJECTIVE: In 2014, the U.S. National Institute on Drug Abuse released the "Principles of Adolescent Substance Use Disorder Treatment," summarizing previously established evidence and outlining principles of effective assessment, treatment, and aftercare for substance use disorders (SUD). Winters et al. (2018) updated these principles to be developmentally appropriate for adolescents. This review builds on that formative work and recommends updated adolescent assessment, treatment, and aftercare principles and practices. METHOD: The Cochrane, MEDLINE-PubMed, and PsychInfo databases were searched for relevant studies with new data about adolescent substance use services. This article updates the 13 original principles; condenses the 8 original modalities into 5 practices; and highlights implications for public policy approaches, future funding, and research. RESULTS: Key recommendations from the principles include integrating care for co-occurring mental health disorders and SUDs, improving service accessibility including through the educational system, maintaining engagement, and addressing tension between agencies when collaborating with other youth service systems. Updates to the treatment practices include adoption of Screening, Brief Intervention and Referral to Treatment (SBIRT), investment in social programs and family involvement in treatment, expanding access to behavioral therapies and medications, increasing funding to harm reduction services, supporting reimbursement for continuing care services, and increasing investment in research. CONCLUSION: These revised principles of adolescent assessment, treatment, and aftercare approaches and practices aim to establish guidance and evidence-based practices for treatment providers, while encouraging necessary support from policymakers and funding agencies to improve the standard of care for adolescent SUD services.

Noninvasive Vagal Nerve Stimulation for Opioid Use Disorder.

Background: Opioid Use Disorder (OUD) is an escalating public health problem with over 100,000 drug overdose-related deaths last year most of them related to opioid overdose, yet treatment options remain limited. Non-invasive Vagal Nerve Stimulation (nVNS) can be delivered via the ear or the neck and is a non-medication alternative to treatment of opioid withdrawal and OUD with potentially widespread applications. Methods: This paper reviews the neurobiology of opioid withdrawal and OUD and the emerging literature of nVNS for the application of OUD. Literature databases for Pubmed, Psychinfo, and Medline were queried for these topics for 1982-present. Results: Opioid withdrawal in the context of OUD is associated with activation of peripheral sympathetic and inflammatory systems as well as alterations in central brain regions including anterior cingulate, basal ganglia, and amygdala. NVNS has the potential to reduce sympathetic and inflammatory activation and counter the effects of opioid withdrawal in initial pilot studies. Preliminary studies show that it is potentially effective at acting through sympathetic pathways to reduce the effects of opioid withdrawal, in addition to reducing pain and distress. Conclusions: NVNS shows promise as a non-medication approach to OUD, both in terms of its known effect on neurobiology as well as pilot data showing a reduction in withdrawal symptoms as well as physiological manifestations of opioid withdrawal.

Association Between Clinician-Level Factors and Patient Outcomes in Virtual and In-Person Outpatient Treatment for Substance Use Disorders: Multilevel Analysis.

BACKGROUND: The use of virtual treatment services increased dramatically during the COVID-19 pandemic. Unfortunately, large-scale research on virtual treatment for substance use disorder (SUD), including factors that may influence outcomes, has not advanced with the rapidly changing landscape. OBJECTIVE: This study aims to evaluate the link between clinician-level factors and patient outcomes in populations receiving virtual and in-person intensive outpatient services. METHODS: Data came from patients (n=1410) treated in a virtual intensive outpatient program (VIOP) and an in-person intensive outpatient program (IOP), who were discharged between January 2020 and March 2021 from a national treatment organization. Patient data were nested by treatment providers (n=58) examining associations with no-shows and discharge with staff approval. Empathy, comfort with technology, perceived stress, resistance to change, and demographic covariates were examined at the clinician level. RESULTS: The VIOP (ß=-5.71; P=.03) and the personal distress subscale measure (ß=-6.31; P=.003) were negatively associated with the percentage of no-shows. The VIOP was positively associated with discharges with staff approval (odds ratio [OR] 2.38, 95% CI 1.50-3.76). Clinician scores on perspective taking (ß=-9.22; P=.02), personal distress (ß=-9.44; P=.02), and male clinician gender (ß=-6.43; P=.04) were negatively associated with in-person no-shows. Patient load was positively associated with discharge with staff approval (OR 1.04, 95% CI 1.02-1.06). CONCLUSIONS: Overall, patients in the VIOP had fewer no-shows and a higher rate of successful discharge. Few clinician-level characteristics were significantly associated with patient outcomes. Further research is necessary to understand the relationships among factors such as clinician gender, patient load, personal distress, and patient retention.

Utility of the Global Appraisal of Individual Needs Recommendation and Referral Report for Substance Use Diagnosis, Treatment Planning, and Placement.

OBJECTIVES: This study aims to evaluate the utility of the Global Appraisal of Individual Needs Recommendation and Referral Report (GRRS) as guided by American Psychiatric Association diagnosis criteria and American Society of Addiction Medicine guidelines for treatment planning and placement. METHODS: Global Appraisal of Individual Needs data were gathered between March 2018 and June 2020 from a total of 82 agencies and 245 clinicians as part of a program evaluation of agencies receiving public funding through the Mid-State Health Network under contract with the Michigan Department of Health and Human Services and the Office of Recovery Oriented Systems of Care. Of the 1395 patients 18 years or older, 1027 GRRS reports were produced by clinical staff. κ And ρ analyses were used to measure rates of clinician agreement with the recommendations produced by the GRRS report based on patient interviews. RESULTS: Clinicians agreed with the GRRS preliminary diagnostic recommendations 88% to 100% of the time, with κ scores indicating excellent agreement by ranging from 0.6 to 0.9. For an average patient, 41 of 46 treatment planning statements generated by the GRRS were used by clinicians, with moderate to high correlation indicated by ρ scores ranging from 0.62 to 0.82. The percent agreement for all American Society of Addiction Medicine dimension ratings was greater than 99%, with κ scores of 0.98 and higher. CONCLUSIONS: This study demonstrates the utility and efficiency of the GRRS as a clinical decision support system to support diagnosis, treatment, and placement in routine practice.

Substance use severity as a predictor for receiving medication for opioid use disorder among adolescents: An analysis of the 2019 TEDS.

BACKGROUND: Medication for opioid use disorder (MOUD) is vastly underutilized in adolescents. Existing treatment guidelines for OUD largely focus on adults, providing limited guidance for pediatric populations. Limited information is known about use of MOUD in adolescents based on substance use severity. METHODS: This secondary data analysis examined how patient-level variables influenced the receipt of MOUD in adolescents aged 12-17 (n = 1866) using the Treatment Episode Data Set (TEDS) 2019 Discharge data set. A crosstabulation and chi-square statistic evaluated the relationship between a proxy for clinical need based on high-risk opioid use (either reporting daily opioid use within the past 30 days and/or history of injection opioid use) for MOUD in states with and without adolescents receiving MOUD (n = 1071). A two-step logistic regression analysis in states with any adolescents receiving MOUD examined the explanatory power of demographic, treatment intake, and substance use characteristics. RESULTS: Completion of 12th grade, a GED, or beyond, decreased the likelihood of receiving MOUD (odds ratio [OR]= 0.38, p = 0.017), as did being female (OR = 0.47, p = .006). None of the remaining clinical criteria were significantly associated with MOUD, although a history of one or more arrests increased the likelihood of MOUD (OR = 6.98, p = 0.06). Only 13% of individuals who met criteria for clinical need received MOUD. CONCLUSIONS: Lower education could serve as a proxy for substance use severity. Guidelines and best practices are needed to ensure the proper distribution of MOUD to adolescents based on clinical need.

Demographic and socioeconomic correlates to buprenorphine access in pharmacies.

BACKGROUND: Research has focused on buprenorphine prescribing with limited attention to the role of pharmacy access to buprenorphine for opioid use disorder. OBJECTIVE: This study examines demographic and socioeconomic correlates to buprenorphine access in Georgia pharmacies. METHODS: A 5-question (12 potential subqueries) telephone administered survey was used to investigate access and stocking patterns of specific dosages and formulations of buprenorphine in Georgia pharmacies (n = 119). Descriptive statistics characterized physician and pharmacy demographics and buprenorphine stocking practices. Correlations between various factors including buprenorphine stocking practices, geographic, and sociodemographic characteristics were identified using nonlinear regression models. RESULTS: The majority of pharmacies stocked the most commonly prescribed 8/2 mg dosage strength of buprenorphine/naloxone films and tablets (69.0% and 63.0%, respectively). Other strengths were less likely to be readily available. Pharmacies in Suburban Census tracts were 77.0% more likely to stock any type of buprenorphine monotherapy [odds ratio (OR) = 1.77, t = 2.37, P < 0.05] and 58.1% more likely to stock the 8 mg buprenorphine monotherapy formulation [OR = 1.58, t = 2.15, P < 0.05] than Urban tracts. Pharmacies in areas with above-average non-White populations were 29.6% more likely to stock a monotherapy product [OR = 1.30, t = 2.16, P < 0.05], and those in areas with above-average poverty rates were more likely to stock the 8 mg/2 mg buprenorphine/naloxone tablets [OR = 1.04, t = 2.02, P < 0.05]. There were no additional differences across the sample in formulation or dosage strengths. Pharmacists who endorsed challenges dispensing buprenorphine (23.3%) cited issues around insurance coverage, payment difficulty, prior authorization issues, and low stock of specific formulations. CONCLUSIONS: Results suggest that low availability of certain dosages or formulations of buprenorphine in local pharmacies could obstruct access for patients. Future research should address barriers to supplying buprenorphine and collaborative measures between pharmacists and prescribers to improve access.

Validating the primary care posttraumatic stress disorder screen for DSM-5 (PC-PTSD-5) in a substance misusing, trauma-exposed, socioeconomically vulnerable population.

The co-occurrence of substance use disorder (SUD) and posttraumatic stress disorder (PTSD) is common, and is associated with greater severity of symptoms, poorer treatment prognosis, and increased risk of return to substance use following treatment. Screening for PTSD is not routinely implemented in substance use treatment programs, despite clinical relevance. Identifying screening tools that minimize patient burden and allow for comprehensive treatment in this patient population is critical. The current study examined the utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) in identifying probable PTSD in a predominantly Black sample of 81 socioeconomically disadvantaged substance misusing hospital patients. The majority of the sample (75.3 %; n = 61) were found to meet criteria for probable PTSD using a suggested clinical cut score of 33 on the PTSD Checklist for DSM-5 (PCL-5). Diagnostic utility analyses were completed and determined a cut-score of 5 for the PC-PTSD-5 to demonstrate the best performance (SE = 0.62, κ(1) = 0.22; SP =.80, κ(0) = 0.61; EEF = 0.67, κ(0.5) = 0.32) in this sample. Results provide preliminary support for the use of the PC-PTSD-5 as a brief screening tool for probable PTSD in substance misusing patient populations. Routine use of the PC-PTSD-5 during assessment may be beneficial when treatment planning with those undergoing treatment for SUD because comprehensive assessment and treatment will provide a better chance of long-term recovery.

Leveraging Accelerometry as a Prognostic Indicator for Increase in Opioid Withdrawal Symptoms.

Treating opioid use disorder (OUD) is a significant healthcare challenge in the United States. Remaining abstinent from opioids is challenging for individuals with OUD due to withdrawal symptoms that include restlessness. However, to our knowledge, studies of acute withdrawal have not quantified restlessness using involuntary movements. We hypothesized that wearable accelerometry placed mid-sternum could be used to detect withdrawal-related restlessness in patients with OUD. To study this, 23 patients with OUD undergoing active withdrawal participated in a protocol involving wearable accelerometry, opioid cues to elicit craving, and non-invasive Vagal Nerve Stimulation (nVNS) to dampen withdrawal symptoms. Using accelerometry signals, we analyzed how movements correlated with changes in acute withdrawal severity, measured by the Clinical Opioid Withdrawal Scale (COWS). Our results revealed that patients demonstrating sinusoidal-i.e., predominantly single-frequency oscillation patterns in their motion almost exclusively demonstrated an increase in the COWS, and a strong relationship between the maximum power spectral density and increased withdrawal over time, measured by the COWS (R = 0.92, p = 0.029). Accelerometry may be used in an ambulatory setting to indicate the increased intensity of a patient's withdrawal symptoms, providing an objective, readily-measurable marker that may be captured ubiquitously.

Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal.

Over 100,000 individuals in the United States lost their lives secondary to drug overdose in 2021, with opioid use disorder (OUD) being a leading cause. Pain is an important component of opioid withdrawal, which can complicate recovery from OUD. This study's objectives were to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS), a technique shown to reduce sympathetic arousal in other populations, on pain during acute opioid withdrawal and to study pain's relationships with objective cardiorespiratory markers. Twenty patients with OUD underwent opioid withdrawal while participating in a two-hour protocol. The protocol involved opioid cues to induce opioid craving and neutral conditions for control purposes. Adhering to a double-blind design, patients were randomly assigned to receive active tcVNS (n = 9) or sham stimulation (n = 11) throughout the protocol. At the beginning and end of the protocol, patients' pain levels were assessed using the numerical rating scale (0-10 scale) for pain (NRS Pain). During the protocol, electrocardiogram and respiratory effort signals were measured, from which heart rate variability (HRV) and respiration pattern variability (RPV) were extracted. Pre- to post- changes (denoted with a Δ) were computed for all measures. Δ NRS Pain scores were lower (P = 0.045) for the active group (mean ± standard deviation: -0.8 ± 2.4) compared to the sham group (0.9 ± 1.0). A positive correlation existed between Δ NRS pain scores and Δ RPV (Spearman's ρ = 0.46; P = 0.04). Following adjustment for device group, a negative correlation existed between Δ HRV and Δ NRS Pain (Spearman's ρ = -0.43; P = 0.04). This randomized, double-blind, sham-controlled pilot study provides the first evidence of tcVNS-induced reductions in pain in patients with OUD experiencing opioid withdrawal. This study also provides the first quantitative evidence of an association between breathing irregularity and pain. The correlations between changes in pain and changes in objective physiological markers add validity to the data. Given the clinical importance of reducing pain non-pharmacologically, the findings support the need for further investigation of tcVNS and wearable cardiorespiratory sensing for pain monitoring and management in patients with OUD.

Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study.

BACKGROUND: Opioid Use Disorder (OUD) is a serious public health problem, and the behavioral and physiological effects of opioid withdrawal can be a major impediment to recovery. Medication for OUD is currently the mainstay of treatment; however, it has limitations and alternative approaches are needed. OBJECTIVE: The purpose of this study was to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on behavioral and physiological manifestations of acute opioid withdrawal. METHODS: Patients with OUD undergoing acute opioid withdrawal were randomly assigned to receive double blind active tcVNS (N = 10) or sham stimulation (N = 11) while watching neutral and opioid cue videos. Subjective opioid withdrawal, opioid craving, and anxiety were measured using a Visual Analogue Scale (VAS). Distress was measured using the Subjective Units of Distress Scale (SUDS), and pain was measured using the Numerical Rating Scale (NRS) for pain. Electrocardiogram signals were measured to compute heart rate. The primary outcomes of this initial phase of the clinical trial (ClinicalTrials.gov NCT04556552) were heart rate and craving. RESULTS: tcVNS compared to sham resulted in statistically significant reductions in subjective opioid withdrawal (p = .047), pain (p = .045), and distress (p = .004). In addition, tcVNS was associated with lower heart rate compared to sham (p = .026). Craving did not significantly differ between groups (p = .11). CONCLUSIONS: tcVNS reduces behavioral and physiological manifestations of opioid withdrawal, and should be evaluated in future studies as a possible non-pharmacologic, easily implemented approach for adjunctive OUD treatment.

Attitudes and beliefs among Georgia addiction treatment staff about medication for opioid use disorder in adolescents, young adults, and adults: a multi-mixed methods study.

Background: Adverse consequences, including non-fatal overdose and death, are prevalent in adolescents and young adults with opioid use disorder (OUD). Barriers toward medication for opioid use disorder (MOUD) have been identified in adult populations but are poorly understood in youth.Objective: This exploratory multi-mixed methods study examines beliefs and attitudes of addiction treatment program staff about the use of MOUD in youth.Methods: A 40-item survey was distributed electronically to 299 addiction treatment programs in Georgia from May 2020 to January 2021. Participant (N = 215; 74% female) attitudes regarding the use of MOUD in three age groups (adolescents (aged 16-17), young adults (aged 18-25), and adults (aged 26+) on a 6-point Likert scale were compared using paired samples t-tests. A series of one-way ANOVA analyses examined differences in attitudes and beliefs across participant characteristics. Verbatim responses to qualitative survey questions were analyzed using a coding reliability approach to thematic analysis.Results: Participants were less likely to support MOUD in adolescents (M = 3.68, SD 1.5) compared with young (M = 4.38, SD 1.36, t = 8.19, p < .001, d = .51) and older adults (M = 4.64, SD 1.3, t = 9.83, p < .001 d = .74). Participants endorsed higher response rates for the use of both naltrexone and buprenorphine over methadone in young adults. A total of 1,412 text responses were reviewed. Participants highlighted barriers to acceptance and use of MOUD in adolescents including safety concerns and impact on brain development.Conclusions: The results support a comprehensive approach to reducing the barriers to using medications to treat OUDs in adolescent populations. Formal and focused continuing education to correct attitudes and beliefs about MOUD treatment for adolescents is necessary.

In-Person Versus Telehealth Setting for the Delivery of Substance Use Disorder Treatment: Ecologically Valid Comparison Study.

BACKGROUND: The COVID-19 pandemic has profoundly transformed substance use disorder (SUD) treatment in the United States, with many web-based treatment services being used for this purpose. However, little is known about the long-term treatment effectiveness of SUD interventions delivered through digital technologies compared with in-person treatment, and even less is known about how patients, clinicians, and clinical characteristics may predict treatment outcomes. OBJECTIVE: This study aims to analyze baseline differences in patient demographics and clinical characteristics across traditional and telehealth settings in a sample of participants (N=3642) who received intensive outpatient program (IOP) substance use treatment from January 2020 to March 2021. METHODS: The virtual IOP (VIOP) study is a prospective longitudinal cohort design that follows adult (aged ≥18 years) patients who were discharged from IOP care for alcohol and substance use-related treatment at a large national SUD treatment provider between January 2020 and March 2021. Data were collected at baseline and up to 1 year after discharge from both in-person and VIOP services through phone- and web-based surveys to assess recent substance use and general functioning across several domains. RESULTS: Initial baseline descriptive data were collected on patient demographics and clinical inventories. No differences in IOP setting were detected by race (χ22=0.1; P=.96), ethnicity (χ22=0.8; P=.66), employment status (χ22=2.5; P=.29), education level (χ24=7.9; P=.10), or whether participants presented with multiple SUDs (χ28=11.4; P=.18). Significant differences emerged for biological sex (χ22=8.5; P=.05), age (χ26=26.8; P<.001), marital status (χ24=20.5; P<.001), length of stay (F2,3639=148.67; P<.001), and discharge against staff advice (χ22=10.6; P<.01). More differences emerged by developmental stage, with emerging adults more likely to be women (χ23=40.5; P<.001), non-White (χ23=15.8; P<.001), have multiple SUDs (χ23=453.6; P<.001), have longer lengths of stay (F3,3638=13.51; P<.001), and more likely to be discharged against staff advice (χ23=13.3; P<.01). CONCLUSIONS: The findings aim to deepen our understanding of SUD treatment efficacy across traditional and telehealth settings and its associated correlates and predictors of patient-centered outcomes. The results of this study will inform the effective development of data-driven benchmarks and protocols for routine outcome data practices in treatment settings.

Telehealth Services for Substance Use Disorders During the COVID-19 Pandemic: Longitudinal Assessment of Intensive Outpatient Programming and Data Collection Practices.

BACKGROUND: The onset of the COVID-19 pandemic necessitated the rapid transition of many types of substance use disorder (SUD) treatments to telehealth formats, despite limited information about what makes treatment effective in this novel format. OBJECTIVE: This study aims to examine the feasibility and effectiveness of virtual intensive outpatient programming (IOP) treatment for SUD in the context of a global pandemic, while considering the unique challenges posed to data collection during an unprecedented public health crisis. METHODS: The study is based on a longitudinal study with a baseline sample of 3642 patients who enrolled in intensive outpatient addiction treatment (in-person, hybrid, or virtual care) from January 2020 to March 2021 at a large substance use treatment center in the United States. The analytical sample consisted of patients who completed the 3-month postdischarge outcome survey as part of routine outcome monitoring (n=1060, 29.1% response rate). RESULTS: No significant differences were detected by delivery format in continuous abstinence (χ22=0.4, P=.81), overall quality of life (F2,826=2.06, P=.13), financial well-being (F2,767=2.30, P=.10), psychological well-being (F2,918=0.72, P=.49), and confidence in one's ability to stay sober (F2,941=0.21, P=.81). Individuals in hybrid programming were more likely to report a higher level of general health than those in virtual IOP (F2,917=4.19, P=.01). CONCLUSIONS: Virtual outpatient care for the treatment of SUD is a feasible alternative to in-person-only programming, leading to similar self-reported outcomes at 3 months postdischarge. Given the many obstacles presented throughout data collection during a pandemic, further research is needed to better understand under what conditions telehealth is an acceptable alternative to in-person care.

Transcutaneous Cervical Vagus Nerve Stimulation Reduces Respiratory Variability in the Context of Opioid Withdrawal.

Opioid withdrawal's physiological effects are a major impediment to recovery from opioid use disorder (OUD). Prior work has demonstrated that transcutaneous cervical vagus nerve stimulation (tcVNS) can counteract some of opioid withdrawal's physiological effects by reducing heart rate and perceived symptoms. The purpose of this study was to assess the effects of tcVNS on respiratory manifestations of opioid withdrawal - specifically, respiratory timings and their variability. Patients with OUD (N = 21) underwent acute opioid withdrawal over the course of a two-hour protocol. The protocol involved opioid cues to induce opioid craving and neutral conditions for control purposes. Patients were randomly assigned to receive double-blind active tcVNS (n = 10) or sham stimulation (n = 11) throughout the protocol. Respiratory effort and electrocardiogram-derived respiration signals were used to estimate inspiration time (Ti), expiration time (Te), and respiration rate (RR), along with each measure's variability quantified via interquartile range (IQR). Comparing the active and sham groups, active tcVNS significantly reduced IQR(Ti) - a variability measure - compared to sham stimulation (p = .02). Relative to baseline, the active group's median change in IQR(Ti) was 500 ms less than the sham group's median change in IQR(Ti). Notably, IQR(Ti) was found to be positively associated with post-traumatic stress disorder symptoms in prior work. Therefore, a reduction in IQR(Ti) suggests that tcVNS downregulates the respiratory stress response associated with opioid withdrawal. Although further investigations are necessary, these results promisingly suggest that tcVNS - a non-pharmacologic, non-invasive, readily implemented neuromodulation approach - can serve as a novel therapy to mitigate opioid withdrawal symptoms.

Trends and age-related disparities in opioid use disorder treatment admissions for adolescents and young adults.

BACKGROUND: Treatment of opioid use disorder (OUD) in adolescents and young adults is imperative to reduce the risk of overdose and other opioid-related harms. Limited information has been published about national trends in health disparities including utilization, access to medication for opioid use disorder (MOUD), and treatment retention of adolescents and young adults with OUD. METHODS: This secondary data analysis tested for trends and age-related disparities in national OUD treatment admissions, as well as length of stay (defined as continuous enrollment in some form of treatment at a program) and planned use of MOUD for adolescents (age 12-17) and young adults (age 18-24) using the Treatment Episode Data Set from 2008 to 2017. The study also used data from the National Survey on Drug Use and Health to identify population prevalence of OUD and presentation to OUD treatment in adolescents and young adults compared to older adults (age 25+). RESULTS: OUD treatment admissions significantly decreased over the decade by 63% (z = 2.61, p < .01) for adolescents and 13% (z = 2.25, p < .01) for young adults. The rate of planned MOUD at intake increased from 1.1% to 3.0% for adolescents but did not achieve significance. MOUD was more commonly recommended in young adults across the time period (13.5 to 21.8%, z = 2.24, p < .01). Treatment length of stay did not change significantly for adolescents, but did increase for young adults from 2008 to 2017 in the 91+ (19.9-23.9%, z = 2.22, p < .01) and 181+ days (9.7-12.5%, z = 2.26, p < .01) categories. Relative to older adults, the percent of people with OUD presenting for OUD treatment is significantly lower for adolescents (44.6% vs. 3.6%, OR = 0.05, p < .05) and young adults (44.6% vs. 22.2%, OR = 0.36, p < .05). Among those who initiated treatment, lower rates occurred of planned MOUD for adolescents (93% vs. 2%, OR = 0.002, p < .05) and young adults (93% vs. 56%, OR = 0.10, p < .05). CONCLUSIONS: A significant unmet need exists for OUD treatment and recommendation of MOUD in adolescents and young adults with OUD. These trends are concerning given increasing rates of opioid-related emergency room admissions and deaths during the same time period. Federal and state funders should examine adolescent and young adult's services separately from older adults (25+) to reduce age-related access disparities and ensure adequate MOUD treatment capacity.

Ibrutinib as a potential therapeutic for cocaine use disorder.

Cocaine use presents a worldwide public health problem with high socioeconomic cost. No current pharmacologic treatments are available for cocaine use disorder (CUD) or cocaine toxicity. To explore pharmaceutical treatments for tthis disorder and its sequelae we analyzed gene expression data from post-mortem brain tissue of individuals with CUD who died from cocaine-related causes with matched cocaine-free controls (n = 71, Mage = 39.9, 100% male, 49% with CUD, 3 samples/brain regions). To match molecular signatures from brain pathology with potential therapeutics, we leveraged the L1000 database honing in on neuronal mRNA profiles of 825 repurposable compounds (e.g., FDA approved). We identified 16 compounds that were negatively associated with CUD gene expression patterns across all brain regions (padj < 0.05), all of which outperformed current targets undergoing clinical trials for CUD (all padj > 0.05). An additional 43 compounds were positively associated with CUD expression. We performed an in silico follow-up potential therapeutics using independent transcriptome-wide in vitro (neuronal cocaine exposure; n = 18) and in vivo (mouse cocaine self-administration; n = 12-15) datasets to prioritize candidates for experimental validation. Among these medications, ibrutinib was consistently linked with the molecular profiles of both neuronal cocaine exposure and mouse cocaine self-administration. We assessed the therapeutic efficacy of ibrutinib using the Drosophila melanogaster model. Ibrutinib reduced cocaine-induced startle response and cocaine-induced seizures (n = 61-142 per group; sex: 51% female), despite increasing cocaine consumption. Our results suggest that ibrutinib could be used for the treatment of cocaine use disorder.

Adaptation and Pilot Testing of the Women's Recovery Group for Young Adults (WRG-YA).

Gender specific substance use disorder treatment has demonstrated promise in adult women, but is relatively unexplored in young adults. To address the specific needs of young adult females, the manual-based Women's Recovery Group (WRG) was adapted for women ages 18-25. Treatment engagement and retention, group cohesiveness, satisfaction, and substance use outcomes were measured during group treatment and at 1-month follow up. This pilot supports the feasibility and initial acceptability of the adapted form of the WRG for young adults. Data from this study may inform future gender specific treatment approaches for substance use disorders in younger populations.