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Migrants and refugees are considered vulnerable to mental health problems and substance use disorders; and may be particularly affected by service disruptions associated with the COVID-19 pandemic The International Society of Addiction Medicine (ISAM) ran a multi-phased global survey among clinicians and health professional that are actively working in the field of addiction medicine to investigate the impact of the COVID-19 pandemic on substance use and related services. In March 2020, the first month after the announcement of the pandemic by the World Health Organization, 177 informants from 77 countries took part in the global survey, and only 12.9% of them reported their countries’ substance use treatment and harm reduction services for the migrants and refugees with substance use disorders continued as usual. In May 2020, 11.7% of respondents of the second phase reported that the services for refugees and migrants improved in comparison to March 2020; 11.7% reported that these services in their country discontinued. Results suggest that refugee and migrants access to treatment and harm reduction services has been reduced as a result of COVID-19. It can be concluded that it is crucial to improve the visibility of migrants’ needs and exploit appropriate interventions for those with substance use disorders.

IntroductionPost-traumatic stress disorder (PTSD) and substance use disorder frequently co-occur and tend to have their onset during adolescence. Although research has highlighted the importance of treating these disorders in an integrated fashion, there is a dearth of empirically validated integrated treatment options for adolescents with this comorbidity. This paper describes the study protocol for a randomised controlled trial (RCT) examining the efficacy of an integrated trauma-focused cognitive–behavioural treatment for traumatic stress and substance use among adolescents (Concurrent Treatment of PTSD and Substance Use Using Prolonged Exposure - Adolescent (COPE-A)), relative to a supportive counselling control condition (Person-Centred Therapy (PCT)).Methods and analysisA two-arm, parallel, single-blind RCT with blinded follow-up at 4 and 12 months poststudy entry will be conducted in Sydney, Australia. Participants (n~100 adolescents aged 12–18 years) and their caregivers (caregiver participation is optional) will be allocated to undergo either COPE-A or PCT (allocation ratio 1:1) using minimisation. Both therapies will be delivered individually by project psychologists over a maximum of 16 sessions of 60–90 min duration and will include provision of up to four 30 min optional caregiver sessions. The primary outcome will be between-group differences in change in the severity of PTSD symptoms from baseline to 4-month follow-up, as measured by the Clinician-Administered PTSD Scale for Children and Adolescents for DSM-5.Ethics and disseminationEthical approval has been obtained from the human research ethics committees of the Sydney Children’s Hospital Network (HREC/17/SCHN/306) and the University of Sydney (HREC 2018/863). Findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numberACTRN12618000785202; Pre-reults.Protocol versionVersion 1, 31 July 2017.

Background Poorly controlled chronic pain can lead to non-prescription use of opiates, which is a growing crisis in our communities. Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic tool which has emerged as a potential treatment option for these patients. It is still unclear, however, if the dorsolateral prefrontal cortex (DLPFC) or the motor cortex (MC) is a more effective treatment location. The purpose of this study was to directly compare the effects of DLPFC versus MC TMS on pain severity and the urge to use opiates among chronic pain patients. Methods Twenty-two individuals with chronic pain currently using prescription opiates were randomized to receive 10, 3000 pulse sessions of 10 Hz repetitive TMS (rTMS) to the left DLPFC (110% resting motor threshold) or left MC (90% resting motor threshold). Multivariate linear models were used to evaluate the effect of TMS on pain and opiate use, including items from the Brief Pain Inventory (BPI) as well as subjective ratings of pain, distress, and the urge for opiates. Results Twenty participants (91%) completed all 10 treatment sessions and follow up visits. There was a main effect of stimulation site (F7,210 = 3.742, p = 0.001), wherein MC stimulation decreased pain interference significantly more than DLPFC stimulation (F1,216 = 8.447, p = 0.004). While both sites had comparable effect sizes on stress, pain, and discomfort, MC stimulation had larger effects on pain interference (Cohen’s d: 0.7) and urge to use opiates (Cohen’s d: 0.5) than DLPFC stimulation. Conclusion These data suggest that the MC may be a promising target for decreasing opiate dependence and pain interference among chronic pain patients.

Background Emergency department-initiated buprenorphine (EDIB) has been shown to be effective in connecting patients with opioid use disorder (OUD) to outpatient treatment. Five diverse emergency departments (EDs) have successfully implemented EDIB programs. Objectives 1) To measure attendance at the first referral appointment and 30-day retention in treatment rates for patients receiving EDIB; 2) To describe demographic and opioid use characteristics of patients receiving EDIB; and 3) To determine average length of time in treatment after EDIB at the five participating EDs. Methods All patients receiving EDIB at the participating EDs (n = 522) were seen by a peer recovery specialist in the ED and demographic and opioid use characteristics were recorded. Patients were followed prospectively. The referral site was contacted and information regarding attendance at the first referral appointment and 30-day retention in treatment was obtained. All patients still in treatment at 30 days were continually followed at subsequent 30-day intervals until the referral site indicated the patient had ended treatment at their facility. Results The rate of attendance at the first referral appointment was 77.0% for patients receiving EDIB. At 30-day follow-up, 43.1% of patients were retained in treatment. The mean age of patient enrollment was 36.7 years, 58% of enrollees were male, 90.5% were white, and 73.4% had no medical insurance. Seventy-seven percent reported no substance use other than opioids. The mean time in treatment was 158 days. Conclusions EDIB programs across diverse ED settings are effective at promoting attendance at the first referral appointment for OUD treatment; however, additional work is warranted to increase 30-day treatment retention rates, particularly among patients with nonprescription-only use profiles.

Post-traumatic stress disorder (PTSD) and substance use disorders (SUDs) frequently co-occur. Among individuals seeking treatment for SUDs, it is estimated that 30–50% meet criteria for lifetime PTSD. Epidemiologic surveys demonstrate that individuals with PTSD are 4–5 times more likely to have a SUD at some point in their lives compared to individuals who do not have PTSD. Self-medication and susceptibility are two hypotheses that have been proposed to help explain the etiological relationship between PTSD and SUDs. It is also possible that common factors, such as genetic, neurobiological, or environmental factors, contribute to the high rate of PTSD-SUD co-occurrence. Integrated psychotherapeutic approaches for the treatment of patients with both disorders show promise. There are also a number of pharmacotherapeutic agents that have demonstrated preliminary efficacy in the treatment of co-occurring PTSD/SUD, but further investigation is needed. This chapter reviews these and other advances in the study of comorbid PTSD and SUDs, and suggests areas for future research and clinical activity.

The co-occurrence of substance use disorders (SUDs) with other psychiatric disorders has been an area of increasing focus over the past 30 years. This intense focus has increased the knowledge base with regard to the prevalence of co-occurring disorders, the neurobiological interface between substance use and other psychiatric disorders, and pharmacologic and psychotherapeutic treatment options. In addition, a critical focus on workforce training and designing systems of care that can optimally address the treatment needs of individuals with co-occurring disorders is needed. In these efforts, sharing knowledge across cultural and national boundaries is essential.

Over the last 25 years, awareness of the significance of gender differences in addiction has grown exponentially in the United States. International studies of gender differences are scarce but growing in number. Understanding gender differences in epidemiology, etiology, risk and protective factors, clinical presentation, psychiatric comorbidity, course of illness, and treatment outcomes of substance use disorders (SUDs), particularly in developing countries, is critical to the implementation of effective treatment and prevention strategies.

Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. Prolonged Exposure (PE) therapy is one of the most widely used evidence-based treatments for PTSD, but there is substantial room for improvement in outcomes and retention rates. Accumulating data suggest that oxytocin offers a promising pharmacological approach towards achieving this goal. Therefore, the primary objective of this two-site Phase II study is to examine the ability of oxytocin (vs. placebo) administration combined with PE therapy to (1) reduce PTSD symptom severity, (2) accelerate the rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, we will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6month follow-up). Intranasal oxytocin (40IU) will be administered directly prior to each PE therapy session. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the physiological mechanisms underlying PTSD and positive treatment response. ClinicalTrials.gov Identifier: NCT04228289.

OBJECTIVE: A substantial amount of individuals with substance use disorders (SUD) also meet criteria for posttraumatic stress disorder (PTSD). Prolonged exposure (PE) is an effective, evidenced-based treatment for PTSD, but there is limited data on its use among individuals with current alcohol or drug use disorders. This study evaluated the efficacy of an integrated treatment that incorporates PE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure or COPE) among veterans. METHOD: Military veterans (N = 81, 90.1% male) with current SUD and PTSD were randomized to 12 sessions of COPE or Relapse Prevention (RP). Primary outcomes included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist-Military version (PCL-M), and the Timeline Follow-back (TLFB). RESULTS: On average, participants attended 8 out of 12 sessions and there were no group differences in retention. Intent-to-treat analyses revealed that COPE, in comparison to RP, resulted in significantly greater reductions in CAPS (d = 1.4, p

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly prevalent and commonly co-occur. The dual diagnosis of PTSD/AUD is associated with serious negative sequalae and there are currently no effective pharmacological treatments for this comorbidity. Both PTSD and AUD are characterized by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which helps modulate stress reactivity. Oxytocin, a neuropeptide that attenuates HPA axis dysregulation, may be beneficial for individuals with co-occurring PTSD/AUD. Thus, the current study examined the effects of intranasal oxytocin (40 IU) as compared to placebo on stress reactivity (e.g., cortisol) as well as subjective alcohol craving in response to a laboratory stress task (Trier Social Stress Task). Participants were 67 male U.S. military veterans with current PTSD and AUD (oxytocin n=32, placebo n=35; overall mean Age=49.06 years). Baseline cortisol levels were examined as a moderator of outcome. The findings revealed that oxytocin marginally attenuated cortisol reactivity in response to the stress task. Furthermore, oxytocin’s effect was moderated by baseline cortisol level, such that oxytocin mitigated cortisol reactivity to a greater extent among participants with higher, as compared to lower, baseline cortisol. Oxytocin did not reduce craving. Although preliminary, the findings are the first to examine oxytocin in co-occurring PTSD/AUD. The findings from this study contribute to the growing literature examining the potential utility of oxytocin among individuals with psychiatric disorders, such as PTSD and substance use disorders. NCT02058251. Keywords: PTSD; alcohol; craving; comorbidity; oxytocin; social stress

Childhood maltreatment is linked to Posttraumatic Stress Disorder (PTSD) in adulthood. Neural attention network function contributes to resilience against PTSD following maltreatment; oxytocin administration alters functional connectivity differentially among resilient to PTSD groups. The present study examined intrinsic connectivity between ventral and dorsal neural attention networks (VAN and DAN) to clarify the nature of dysfunction versus resilience in the context of maltreatment-related PTSD, and to explore differential dysfunction related to varied aspects of maltreatment. Oxytocin administration was examined as a factor in these relationships. Resting-state functional connectivity data were collected from 39 adults with maltreatment histories, with and without PTSD, who were randomly assigned to receive oxytocin or placebo. We found that PTSD and sexual abuse (SA) were associated with reduced VAN-DAN connectivity. There were no significant effects with regard to physical abuse. Oxytocin was associated with greater VAN-DAN connectivity strength. These preliminary findings suggest dysfunction within attentional systems in PTSD, as well as following SA. Further, oxytocin may help ameliorate attentional neurocircuitry dysfunction in individuals with PTSD and those with maltreatment histories.

Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition for which effective medications are scant and little is known about neural correlates of risk versus resilience. Oxytocin is a hypothalamic neuropeptide that has demonstrated promise in modulating neurobiological and behavioral correlates of PTSD. Cognitive deficits in areas such as working memory and executive control are highly prevalent among individuals with PTSD and oxytocin might modulate these impairments in individuals with PTSD. Using a double-blind, placebo-controlled design, this study employed functional magnetic resonance imaging (fMRI) and the N-back working memory task to examine the effects of oxytocin (24 IU) versus placebo on working memory and dorsolateral prefrontal cortex connectivity among individuals with PTSD (n=16) as compared to a trauma-exposed control group (n=18). Results indicate that individuals with PTSD on oxytocin performed better in the 2-back condition of the N-back task compared to individuals with PTSD on placebo. Results also indicate that connectivity between dorsolateral prefrontal cortex and anterior cingulate increased in the 2-back condition among individuals with PTSD on oxytocin as compared to placebo. These findings provide preliminary evidence of an effect of oxytocin on working memory among individuals with PTSD and insights into the neurobiological mechanisms underlying this association. Future studies are necessary to understand the mechanisms responsible for working memory deficits in PTSD and to examine the potential of oxytocin for use as a treatment for PTSD. NCT01963078

Social stress, especially dyadic conflict among couples, is an important correlate of addiction. Several authors have suggested that the neuropeptide oxytocin (OT) may be useful in the treatment of couples with substance misuse. However, the literature examining OT among couples is scant and has yielded mixed findings. The current study examined the effects of OT versus placebo on emotional (e.g., warmth and anger) and physiological (e.g., skin conductance and heart rate) reactivity to a conflict resolution task in 30 heterosexual couples (N=60) in which one or both members misused substances. Using a randomized, double-blind, placebo-controlled design, both partners within each dyad were randomized to the same treatment condition. Participants completed a standardized conflict resolution task at baseline and 45 minutes following drug self-administration. Physiological measures were examined continuously during the laboratory tasks and emotional reactivity was self-reported at baseline and at 5 time points over the course of 1 hour following the second conflict resolution task. Results of a multi-level growth curve model accounting for baseline scores, gender and drug condition indicate that positive emotional experiences and skin conductance measures increased over the 5 time points. Neither drug condition nor gender was significantly related to outcomes, and no interaction effects were observed. These findings highlight the complexities involved in translational OT research and suggest that the impact of OT on key outcomes requires further exploration in regards to OT's potential therapeutic benefit.

Introduction South Carolina has experienced a surge in fatal overdoses, primarily fueled by opioid-involved overdose deaths. This work aims to quantify the burden of premature mortality due to fatal opioid-involved overdoses in South Carolina while documenting the contribution of synthetic opioids to excess mortality, examining substance specific geographic and demographic patterns of mortality burden, and measuring the effect of fatal opioid and synthetic opioid-involved overdoses on average lifespan. Methods We obtained death certificates for fatalities involving opioids, cocaine, benzodiazepines, and psychostimulants (N = 3,726) in South Carolina from 2014 to 2018. Years of Potential Life Lost (YPLL), was used to examine gender, racial, and geographic disparities in mortality burden. We assessed the contribution of synthetic opioid poisoning to the overall opioid mortality burden over time and calculated the effect of fatal opioid and synthetic opioid-involved overdoses on average lifespan. Results From 2014 to 2018, opioid-involved overdose deaths resulted in 124,451 YPLL. The average age of fatal male and female opioid-involved overdoses decreased 2.8 and 3.9 years, respectively. Synthetic opioids increasingly contributed to opioid YPLL, accounting for 22% in 2014 to 64% in 2018. Mortality burden was not shared equally between races, sexes, or rural/urban counties. The largest change occurred in black male synthetic opioid-involved deaths (2234%). Rural counties comprised 44-48% of the population adjusted YPLL despite containing 34% of the population. Conclusion Opioid-involved overdoses account for a critical cause of mortality in South Carolina, demonstrate significant impact on YPLL and highlight mortality burden disparities in gender, race, and rural/urban settings.

Cocaine dependence is a chronic and relapsing disorder which is particularly resistant to behavioral or pharmacologic treatment, and likely involves multiple dysfunctional frontal-striatal circuits. Through advances in preclinical research in the last decade, we now have an unprecedented understanding of the neural control of drug-taking behavior. In both rodent models and human clinical neuroimaging studies, it is apparent that medial frontal-striatal limbic circuits regulate drug cue-triggered behavior. While non-human preclinical studies can use invasive stimulation techniques to inhibit drug cue-evoked behavior, in human clinical neuroscience, we are pursuing non-invasive theta burst stimulation (TBS) as a novel therapeutic tool to inhibit drug cue-associated behavior. Our laboratory and others have spent the last 7 years systematically and empirically developing a non-invasive, neural circuit-based intervention for cocaine use disorder. Utilizing a multimodal approach of functional brain imaging and brain stimulation, we have attempted to design and optimize a repetitive transcranial magnetic stimulation treatment protocol for cocaine use disorder. This manuscript will briefly review the data largely from our own lab that motivated our selection of candidate neural circuits, and then summarize the results of six studies, culminating in the first double-blinded, sham-controlled clinical trial of TMS as a treatment adjuvant for treatment-engaged cocaine users (10 sessions, medial prefrontal cortex, 110% resting motor threshold, continuous theta burst stimulation, 3600 pulses/session). The intent of this review is to highlight one example of a systematic path for TMS treatment development in patients. This path is not necessarily optimal, exclusive, or appropriate for every neurologic or psychiatric disease. Rather, it is one example of a reasoned, empirically derived pathway which we hope will serve as scaffolding for future investigators seeking to develop TMS treatment protocols.

There are limited data about the extent of DSM-5 substance use disorders (SUDs) among primary care patients.This study analyzed data from a multisite validation study of a substance use screening instrument conducted in a diverse sample of 2000 adults aged ≥18 years recruited from five primary care practices in four states. Prevalence and correlates of 12-month DSM-5 SUDs were examined.Overall, 75.5% of the sample used any substance, including alcohol (62.0%), tobacco (44.1%), or illicit drugs/nonmedical medications (27.9%) in the past 12 months (marijuana 20.8%, cocaine 7.3%, opioids 4.8%, sedatives 4.1%, heroin 3.9%). The prevalence of any 12-month SUD was 36.0% (mild disorder 14.2%, moderate/severe disorder 21.8%): tobacco 25.3% (mild 11.5%, moderate/severe 13.8%); alcohol 13.9% (mild 6.9%, moderate/severe 7.0%); and any illicit/nonmedical drug 14.0% (mild 4.0%, moderate/severe 10.0%). Among past 12-month users, a high proportion of tobacco or drug users met criteria for a disorder: tobacco use disorder 57.4% (26.1% mild, 31.3% moderate/severe) and any drug use disorder 50.2% (14.3% mild, 35.8% moderate/severe); a lower proportion of alcohol users (22.4%) met criteria for alcohol use disorder (11.1% mild, 11.3% moderate/severe). Over 80% of adults with opioid/heroin use disorder met criteria for a moderate/severe disorder. Younger ages, male sex, and low education were associated with increased odds of having SUD.These findings reveal the high prevalence of SUDs in primary care and underscore the need to identify and address them.

OBJECTIVE: Given changes in U.S. marijuana laws, attitudes, and use patterns, individuals with pain may be an emerging group at risk for nonmedical cannabis use and cannabis use disorder. The authors examined differences in the prevalence of nonmedical cannabis use and cannabis use disorder among U.S. adults with and without pain, as well as whether these differences widened over time. METHODS: Data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, 2001–2002; N=43,093) and NESARC-III (2012–2013; N=36,309) were analyzed using logistic regression. Risk differences of past-year nonmedical cannabis use, frequent (at least three times a week) nonmedical use, and DSM-IV cannabis use disorder were estimated for groups with and without moderate to severe pain, and these risk differences were tested for change over time. RESULTS: Any nonmedical cannabis use was more prevalent in respondents with than without pain (2001–2002: 5.15% compared with 3.74%; 2012–2013: 12.42% compared with 9.02%), a risk difference significantly greater in the 2012–2013 data than in the 2001–2002 data. The prevalence of frequent nonmedical cannabis use did not differ by pain status in the 2001–2002 survey, but was significantly more prevalent in those with than without pain in the 2012–2013 survey (5.03% compared with 3.45%). Cannabis use disorder was more prevalent in respondents with than without pain (2001–2002: 1.77% compared with 1.35%; 2012–2013: 4.18% compared with 2.74%), a significantly greater risk difference in the data from 2012–2013 than from 2001–2002. CONCLUSIONS: The results suggest that adults with pain are a group increasingly vulnerable to adverse cannabis use outcomes, warranting clinical and public health attention to this risk. Psychiatrists and other health care providers treating patients with pain should monitor such patients for signs and symptoms of cannabis use disorder.

Background Emergency department-initiated buprenorphine (EDIB) programs have been shown to improve treatment outcomes for patients with opioid use disorders (OUD); however, little is known about how EDIB implementation impacts the patient census at participating hospitals. Objectives To determine if implementation of an EDIB program was associated with changes in the number of patients presenting to the ED seeking treatment for substance use disorder (SUD). Methods We conducted a retrospective evaluation at a single academic ED that began offering EDIB in December 2017. Data span the period of December 2016 to April 2019, All ED visits with a chief complaint of addiction problem, detoxification, drug/alcohol assessment, drug problem, or withdrawal charted by nursing at the time of triage were eligible for inclusion. Charts were reviewed to determine: (1) treatment status and (2) substance(s) for which the patient was seeking treatment. An interrupted time series analysis was used to compare the pre- and post-EDIB rates for all-substance, as well as opioid-specific, treatment-seeking visits. Results For all-substance visits, the predicted level change in the treatment-seeking rate after EDIB was implemented was positive but not significant (0.000497, p = 0.53); the trend change after EDIB was also not significant (−0.00004, p = 0.73). For visits involving opioids, the predicted level change was (0.000638, p = 0.21); and the trend change was (0.000047, p = 0.49). Conclusion Implementation of an EDIB program was not associated with increased rates of presentation by patients requesting treatment for a substance use disorder in the participating ED setting.

Background: Posttraumatic stress disorder (PTSD) related to exposure to abuse and neglect during childhood is associated with particularly severe and persistent deleterious outcomes. Amygdala hyperreactivity has been observed in childhood trauma survivors and implicated in symptoms of PTSD. Objective: The neuropeptide oxytocin holds promise as a potential treatment for PTSD due to its ability to attenuate amygdala response to threat cues. However, the effect of oxytocin on amygdala reactivity in individuals with childhood trauma-related PTSD has not been investigated. Method: We employed a double-blind, randomized, placebo-controlled crossover design to examine the effects of intranasal oxytocin (24 IU) versus placebo on amygdala reactivity to fearful faces among childhood-trauma exposed individuals with PTSD (n = 17) and without PTSD (control group; n = 16). Results: Region-of-interest based amygdala fMRI signal magnitude did not differ by group, drug, or group x drug interaction. Self-report of childhood trauma exposure severity was negatively associated with the oxytocin-related change in left amygdala response in the PTSD group, but not in the control group. Supplementary and exploratory whole-brain analyses conducted separately in each group revealed that left amygdala reactivity to fearful faces was absent on placebo but increased on oxytocin in the control group. The PTSD group showed right amygdala activation to fearful faces in both the oxytocin and placebo conditions, but the left amygdala response observed in the placebo condition was diminished on oxytocin. Conclusions: Findings extend the literature pertaining to the potential for oxytocin to attenuate neural correlates of PTSD to a childhood trauma-related PTSD sample.

Aim The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN), an entity aimed at bridging researchers and community-based substance abuse treatment providers to develop new treatment approaches, has taken an interest in the dissemination of findings from a randomized clinical trial by D'Onofrio demonstrating that initiating buprenorphine in the emergency department (ED) enhances linkage to treatment [JAMA 2015; 313 (16): 1636–1644]. In the Southern Consortium Node of the CTN, the authors have taken an implementation science approach to expand on the D'Onofrio study by implementing an ED-based buprenorphine initiation program in three diverse South Carolina EDs utilizing a predominantly peer recovery coach model. The aim of this pilot program was to foundationally integrate universal screening, brief interventions and referral to treatment (SBIRT) in hospital EDs to identify patients with at-risk substance use. Through brief interventions, patient navigators assessed readiness to change and motivation for treatment of patients. Patients willing to engage in treatment were referred to appropriate community resources. Patients identified to have opioid use disorder (OUD) and willing to engage in treatment were eligible for ED-initiated buprenorphine and peer recovery coaches assisted in arranging next day follow up with a community treatment program or other local provider for ongoing treatment. Method Hospital partner sites included a large academic medical center, a large private hospital, and a small community hospital. Prior to implementing this quality improvement initiative, the authors completed an ED workflow analysis at each site, developed internal planning committees including identification of a “hospital champion,” facilitated electronic health record modifications, educated more than 200 ED nurses and providers, and identified a network of local community “fast-track” providers able to accept patients for next-day appointments. Results Within 14 months, all three sites were fully operationalized and project staff in 3 ED sites screened 6523 patients for substance misuse with 33.0% screened positive for at-risk substance use. Positive screening results were as follows by substance: 907 alcohol, 100 cocaine, 40 methamphetamine, 7 amphetamines, 96 marijuana, 12 benzodiazepines, 3 Ecstasy/MDMA/Molly, 10 other/unknown substance, 274 heroin, 90 prescription opioids, 32 other/unknown opioid, 254 undetermined polysubstance use without opioids, and 331 polysubstance use with opioids. Of the 727 positive screened patients for non-medical opioid use, 70.0% were determined potentially eligible to receive buprenorphine initiation. Two-hundred thirty-one patients were initiated with one dose of 8 mg sublingual buprenorphine or 8-2 mg sublingual buprenorphine/naloxone; 76.6% of those initiated arrived to next-day appointments for continued medications for opioid use disorder (MOUD); and 59.9% of those patients were retained in treatment at 30 days. Of referred patients, payor at time of ED visit were as follows: 71.1% uninsured, 21.4% state Medicaid, 1.6% Medicare, and 5.9% private health insurance. Conclusion With adequate resources and institutional support, implementation of evidence-based quality improvement initiatives focused on OUDs are feasible and enhance linkage to evidence-based treatment in a rural Southern state. Lessons learned from this implementation study can be used to guide future CTN studies focused on ED settings. Project support Financially supported by South Carolina Department of Health and Human Services with consultation and guidance from Mosaic Group and South Carolina Department of Alcohol and Other Drug Services.

Relationship conflict and distress negatively impacts psychological and physical health and is saliently associated with substance misuse (Baucom et al., 1998; McCrady et al., 2016; Schumm, O'Farrell, & Andreas, 2012). Conversely, adaptive couple functioning is central to positive treatment engagement and outcomes for substance use disorders (McCrady et al., 2016; Powers, Vedel, & Emmelkamp, 2008). The neuropeptide oxytocin (OT) has demonstrated beneficial effects on social cognition and prosocial behavior and has shown therapeutic potential in the treatment of various psychiatric conditions including substance use disorders (e.g., Flanagan, Sippel, Wahlquist, Moran-Santa Maria, & Back, 2018b). OT might prove useful as an adjunct treatment for behavioral therapies with couples, including those targeting substance-misusing individuals who are prone to have difficulty managing conflict in intimate relationships (Cranford, Floyd, Schulenberg, & Zucker, 2011) due to OT’s potential to ameliorate stress reactivity and to increase trust, emotional recognition, and cooperation (Bakermans-Kranenburg & van Ijzendoorn, 2013; Ditzen et al., 2009; Keri & Kiss, 2011; Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005; Mitchell, Gillespie, & Abu-Akel, 2015). However, more research is needed given some findings that reveal a seemingly inconsistent effect of OT on social behavior (Bartz, Zaki, Bolger, & Ochsner, 2011b; Mitchell, Arcuni, Weinstein, & Woolley, 2016; Shamay-Tsoory & Abu-Akel, 2016). The social salience hypothesis posits that OT may amplify an individual’s pre-existing social inclinations, rather than universally enhance prosocial behavior and cognition (Shamay-Tsoory & Abu-Akel, 2016). For example, OT’s effects have been found to vary based on person and context (Bartz et al., 2011b), such as familiarity and anticipated threat. Although early evidence suggests beneficial effects of OT on couple functioning (Ditzen et al., 2009), more recent literature suggests that various individual and situational factors modulate social behavior responses to OT (Bartz et al., 2011a; DeWall et al., 2014; Jarnecke, Barden, Back, Brady, & Flanagan, 2018). Thus, OT may not exclusively promote adaptive conflict behaviors among couples, but could potentially increase negative affect and conflict behaviors in the context of specific individual or contextual vulnerabilities. It is necessary, therefore, to examine the contextual relationship factors that may moderate OT response in couples in order to identify for whom and under what circumstances OT is most beneficial. One relationship factor that might influence OT response is infidelity; that is, sexual, romantic, or emotional involvement that breaches the commitment to an exclusive romantic relationship (Glass, 2002). Both emotional infidelity and physical infidelity can cause deleterious relationship and health outcomes (Marin, Christensen, & Atkins, 2014; Whisman, 2016). Infidelity has been identified as the most frequent self-reported cause of divorce (Amato & Previti, 2003) and is associated with depression (Cano & O'Leary, 2000), low self-esteem (Charny & Parnass, 1995), and intimate partner violence (Carbone-Lopez, Kruttschnitt, & Macmillan, 2006; Nemeth, Bonomi, Lee, & Ludwin, 2012). Thus, infidelity may represent a relational vulnerability that modulates reactivity to OT; however no previous studies to date have examined the role of infidelity in OT response. In line with the social salience hypothesis of OT (Shamay-Tsoory & Abu-Akel, 2016), instead of OT generally increasing positive and decreasing negative communication, infidelity may serve as a maladaptive contextual vulnerability that influences OT-related effects on conflict behaviors. The current study is designed to address this gap in the literature. Specifically, we examined whether infidelity moderates the association between OT and dyadic conflict behaviors in a sample of couples with substance misuse. This study extends prior research by examining these associations within a dyadic framework to account for both actor (e.g., how much one’s current behavior is predicted by his/her own behavior) and partner effect (e.g., how much one’s behavior is influence by his/her partner’s behavior). We hypothesized that actor and partner infidelity would (1) be associated with less adaptive conflict behaviors, and (2) moderate the OT response, such that participants randomized to the OT condition, compared to placebo, who report more infidelity would show less adaptive conflict behaviors.

PurposeTo enhance understanding of challenges related to work-life integration in academic medicine and to inform the ongoing implementation of an existing program and the development of other interventions to promote success of physician-scientists.MethodThis study is part of a prospective analysis of the effects of the Fund to Retain Clinical Scientists (FRCS), a national program launched by the Doris Duke Charitable Foundation at 10 U.S. institutions, which provides financial support to physician-scientists facing caregiving challenges. In early 2018, 28 of 33 program awardees participated in semistructured interviews. Questions were about challenges faced by physician-scientists as caregivers and their early perceptions of the FRCS. Multiple analysts reviewed deidentified transcripts, iteratively revised the coding scheme, and interpreted the data using qualitative thematic analysis.ResultsParticipants' rich descriptions illuminated 5 interconnected themes: (1) Time is a critical and limited resource, (2) timing is key, (3) limited time resources and timing conflicts may have a particularly adverse effect on women's careers, (4) flexible funds enable reclamation and repurposing of time resources, and (5) FRCS leaders should be cognizant of time and timing conflicts when developing program-related offerings.ConclusionsPrograms such as the FRCS are instrumental in supporting individuals to delegate time-consuming tasks and to control how they spend their valuable time. Qualitative analysis suggests that access to and command of valuable time resources are crucial to career advancement, research productivity, and work-life flexibility, especially during critical time points along the physician-scientist trajectory.

Cocaine use disorder (CUD) is a major public health concern with devastating social, economic, and mental health implications. A better understanding of the underlying neurobiology and phenotypic variations in individuals with CUD is necessary for the development of effective and targeted treatments. In this study, 39 women and 54 men with CUD completed a 6-min resting-state functional magnetic resonance imaging scan after intranasal oxytocin (OXY) or placebo administration. Graph-theory network analysis was used to quantify functional connectivity changes caused by OXY in striatum, anterior cingulate cortex (ACC), insula, and amygdala nodes of interest. OXY increased connectivity in the right ACC and left amygdala in males, whereas OXY increased connectivity in the right ACC and right accumbens in females. Machine learning was then used to associate treatment response (placebo minus OXY) in nodes of interest with years of cocaine use and severity of childhood trauma separately for males and females. Childhood trauma and years of cocaine use were associated with OXY-induced changes in ACC connectivity for both men and women, but connectivity changes in the amygdala were associated with years of cocaine use in men and connectivity changes in the right insula were associated with years of cocaine use in women. These findings suggest that salience network nodes (ACC and insula) are potential OXY treatment targets in CUD, with the amygdala as a treatment target for men and the accumbens as a treatment target for women.

Opioid use disorder (OUD) has been declared a national crisis, as prevalence of OUD has increased remarkably over the past decade (Jones, 2017). While Medication Assisted Treatment (MAT) is the standard of care for OUDs, several key barriers to implementation have been noted throughout the clinical and research literature (DeFlavio et al., 2015). As a first step toward enhancing implementation and dissemination of MAT across the state of South Carolina, a needs assessment was conducted with key persons from 33 agencies to inform our efforts. Results provided descriptive information regarding medical providers and patients seen within agencies. Of the 33 agencies, 6 agencies (18%) reported having buprenorphine-waivered providers on staff (total of 11 medical providers across the 6 agencies). Agencies reported that they referred a mean of 4.63 patients to other facilities for MAT in the past month. Barriers to providing MAT were identified, with the most significant barrier including the lack of medical staff to prescribe buprenorphine (47%). Overall, the current study reiterates the gap between treatment need and capacity for OUD patients, and highlights factors associated with barriers to MAT adoption in state-funded county drug and alcohol agencies across a southern, predominantly rural state.

SPARCRequest© (Services, Pricing, & Application for Research Centers) is a web-based research management system that provides a modular and adaptable “electronic storefront” for research-related services. Developed by the South Carolina Clinical & Translational Research Institute at the Medical University of South Carolina, it was released as open source (OS) code in 2014. The adoption of SPARCRequest© accelerated in 2016, when, to ensure responsiveness to the needs of partners, its governance also became open. This governance model enables OS partners to suggest and prioritize features for new releases. As a result, the software code has become more modularized and can be easily customized to meet the diverse needs of adopting hubs. This article describes innovative aspects of the OS governance model, including a multi-institutional committee structure to set strategic vision, make operational decisions, and develop technical solutions; a virtual roadmap that ensures transparency and aligns adopters with release-based goals; and a business process model that provides a robust voting mechanism for prioritizing new features while also enabling fast-paced bug fixes. OS software evolves best in open governance environments. OS governance has made SPARCRequest© more responsive to user needs, attracted more adopters, and increased the proportion of code contributed by adopters.

This chapter discusses the primary components of COPE and provides a brief overview of prolonged exposure therapy, and present outcomes to date. COPE provides an integrated, evidence-based treatment to reduce posttraumatic stress disorder (PTSD) and substance use disorders (SUD) severity within the same treatment episode, thereby alleviating the need for clients to first go to one provider for SUD treatment and then go to another provider for PTSD treatment. Providers are encouraged to use their clinical judgment in prioritizing the information and activities during the course of COPE therapy in order to best meet each client’s unique needs. In COPE, imaginal exposure generally lasts 30–45 minutes per session and involves the client revisiting the memory of the trauma and describing it out loud in the present tense and in as much detail as possible. In COPE, cravings as well as anxiety/distress are also assessed before and after imaginal and in vivo exposures.

Introduction: The American Dental Association recommends that dentists use a prescription drug monitoring program (PDMP) prior to prescribing an opioid for acute pain management. Objective: The objective of this study was to examine dentists’ experiences using their state PDMP, as well as the impact that state-mandated registration policies, mandated use policies, and practice characteristics had on the frequency with which dentists used their PDMP. Methods: We conducted a web-based cross-sectional survey among practicing dentist members of the National Dental Practice-Based Research Network ( n = 805). The survey assessed prescribing practices for pain management and implementation of risk mitigation strategies, including PDMP use. Survey data were linked with network Enrollment Questionnaire data to include practitioner demographics and practice characteristics. Results: Nearly half of respondents ( n = 375, 46.6%) reported having never accessed a PDMP, with the most common reasons for nonaccess being lack of awareness ( n = 214, 57.1%) and lack of knowledge regarding registration and use ( n = 94, 25.1%). The majority of PDMP users reported the program to be very helpful (58.1%) or somewhat helpful (31.6%). Dentists reported that PDMP use most often did not change their intended prescribing behavior (40.2%), led them not to prescribe an opioid (33.5%), or led them to prescribe fewer opioid doses (25.5%). Presence of a mandated use policy was significantly associated with increased frequency of PDMP use across a variety of situations, including prior to 1) prescribing any opioid for pain management, 2) issuing refills, 3) prescribing to new patients, and 4) prescribing to patients deemed high risk. Conclusion: Findings suggest that the majority of dentists find PDMPs helpful in informing their opioid-prescribing practices. Whereas the existence of a state-mandated use policy is a consistent predictor of dentists’ PDMP use, outreach and education efforts may overcome key barriers to use identified in this study. Knowledge Transfer Statement: Findings from this national survey suggest that the majority of practicing dentists find PDMPs helpful in informing their opioid-prescribing practices; however, consistent PDMP use was not common. Whereas the existence of a state-mandated use policy is a consistent predictor of dentists’ PDMP use, outreach and education efforts may overcome key barriers to use identified in this study.

BACKGROUND Mental health and alcohol use problems are among the most common causes of disease burden in young Australians, frequently co-occur (comorbidity), and lead to significant lifetime burden. However, comorbidities remain significantly underdetected and undertreated in health settings. Digital mental health tools designed to identify at-risk individuals, encourage help-seeking, or deliver treatment for comorbidity have the potential to address this service gap. However, despite a strong body of evidence that digital mental health programs provide an effective treatment option for a range of mental health and alcohol use problems in young adults, research shows that uptake rates can be low. Thus, it is important to understand the factors that influence treatment satisfaction and quality-of-life outcomes for young adults who access e–mental health interventions for comorbidity. OBJECTIVE In this study, we seek to understand the factors that influence treatment satisfaction and quality-of-life outcomes for young adults who access e–mental health interventions for comorbid alcohol and mood disorders. The aim is to determine the importance of personality (ie, Big Five personality traits and intervention attitudes), affective factors (ie, depression, anxiety, and stress levels), and baseline alcohol consumption in predicting intervention trial engagement at sign-up, satisfaction with the online tool, and quality of life at the end of the iTreAD (Internet Treatment for Alcohol and Depression) trial. METHODS Australian adults (N=411) aged between 18 and 30 years who screened positive for depression and alcohol use problems signed up for the iTreAD project between August 2014 and October 2015. During registration, participants provided information about their personality, current affective state, alcohol use, treatment expectations, and basic demographic information. Subsequent follow-up surveys were used to gauge the ongoing trial engagement. The last follow-up questionnaire, completed at 64 weeks, assessed participants’ satisfaction with web-based treatment and quality-of-life outcomes. RESULTS Multiple linear regression analyses were used to assess the relative influence of predictor variables on trial engagement, treatment satisfaction, and quality-of-life outcomes. The analyses revealed that the overall predictive effects of personality and affective factors were 20% or lower. Neuroticism constituted a unique predictor of engagement with the iTreAD study in that neuroticism facilitated the return of web-based self-assessments during the study. The return of incentivized follow-up assessments predicted treatment satisfaction, and state-based depression predicted variance in quality-of-life reports at study completion. CONCLUSIONS Our findings suggest that traditional predictors of engagement observed in face-to-face research may not be easily transferable to digital health interventions, particularly those aimed at comorbid mental health concerns and alcohol misuse among young adults. More research is needed to identify what determines engagement in this population to optimally design and execute digital intervention studies with multiple treatment aims. CLINICALTRIAL Australian New Zealand Clinical Trials Registry (ACTRN): 12614000310662; http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365137&isReview=true. INTERNATIONAL REGISTERED REPORT RR2-10.1186/s12889-015-2365-2

Background Hospitalization with co-occurring opioid use disorder (OUD) and infections presents a critical time to intervene to improve outcomes for these intertwined epidemics that are typically managed separately. A surge in life-threatening infectious diseases associated with injection drug use, including bacterial and fungal infections, HIV, and HCV accounts for substantial healthcare utilization, morbidity, and mortality. Infectious Disease (ID) specialists manage severe infections that require hospitalization and are a logical resource to engage patients in medication treatment for OUD (MOUD). An injectable long-acting monthly formulation of buprenorphine (LAB) has a potential advantage for initiating MOUD within hospital settings and bridging to treatment after discharge. Methods A randomized multi-site trial tests a new model of care (ID/LAB) in which OUD and infections are managed by ID specialists and hospitalists using LAB coupled with referrals to community resources for long-term MOUD. A sample of 200 adults admitted to three U.S. hospitals for OUD and infections are randomly assigned 1:1 to ID/LAB or treatment as usual (TAU). The primary outcome measure is the proportion of patients enrolled in effective MOUD at 12 weeks after randomization. Secondary outcomes include relapse to opioid use, adherence to infectious disease treatment, infection morbidity and mortality, and drug overdose. Results We describe the design, procedures, statistical analysis, and early implementation issues of this randomized trial. Conclusions Study findings will provide insight into the feasibility and effectiveness of integrated treatment of OUD and serious infections and have the potential to reduce morbidity and mortality in this vulnerable population.

Objectives Posttraumatic stress disorder (PTSD) and substance use disorders are highly comorbid. Effective treatments are largely lacking. This pilot study evaluated the safety and feasibility of a novel intervention, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), in preparation for a randomized controlled trial. Methods Twenty-two treatment-seeking women with current DSM-IV-TR PTSD and alcohol dependence (AD) were recruited. Participants received COPE. Safety and feasibility were evaluated, as were efficacy-related outcomes: PTSD and depression symptom severity, alcohol use, craving, and dependence severity. Results No adverse events occurred. COPE was implemented in routine clinical practice. Among the assessed women, 95.8% were eligible to participate. Treatment attendance and completion were higher than in previous studies. Post treatment, all efficacy-related outcomes, including PTSD and depression symptom severity, alcohol use, craving, and dependence severity, were significantly reduced. Conclusions COPE was safe and feasible to use. Concerns that trauma-focused, exposure-based therapy might promote relapse in this population appear unwarranted. Our findings provide initial evidence suggestive of COPE efficacy for comorbid PTSD and AD in women. These results provide a strong rationale for investigating the efficacy of COPE for comorbid PTSD and AD in women in a randomized controlled trial.

This paper reviews the current literature on clinical guidelines, practitioner training, and government/payer policies that have come forth in response to the national rise in prescription opioid overdoses. A review of clinical opioid prescribing guidelines highlights the need for more research on safe and effective treatment options for chronic pain, improved guidance for the best management of post-operative pain, and evaluation of the implementation and impact of guideline recommendations on patient risk and outcomes. Although there is increasing attention to training in pain management in medical schools and medical residency programs, educational opportunities remain highly variable, and the need for additional clinician training in the recognition and treatment of pain as well as opioid use disorder has been recognized. Mandated use of private, federal and state educational and clinical initiatives such as Risk Evaluation and Mitigation Strategies (REMS) and Prescription Drug Monitoring Programs (PDMPs) generally increase utilization of these initiatives, but more research is needed to determine the impact of these initiatives on provider behaviors, treatment access, and patient outcomes. Finally, there is an acute need for more research on safe and effective treatments for chronic pain as well as an increased multi-level focus on improving training and access to evidence-based treatment for opioid use disorder as well as non-pharmacologic and non-interventional chronic pain treatments, so that these guideline-recommended interventions can become mainstream, accessible, first-line interventions for chronic pain and/or opioid use disorders.

Responses to stress may be important in understanding gender differences in substance use disorders and may also be a target for development of treatment interventions. A growing body of both preclinical and clinical research supports important underlying gender differences in the corticotropin-releasing factor (CRF) and noradrenergic systems, which may contribute to drug use. Preclinical models have demonstrated increased sensitivity of females to CRF and noradrenergic-induced drug reinstatement compared with males, and, consistent with these findings, human laboratory studies have demonstrated greater sensitivity to corticotropin-releasing hormone (CRH) and noradrenergic stimulation in cocaine-dependent women compared with men. Furthermore, neuroimaging studies have demonstrated increased neural response to stressful stimuli in cocaine-dependent women compared with men as well as showing significant sex differences in the sensitivity of brain regions responsible for regulating the response to CRH. Development of interventions targeting the noradrenergic system and stress response in drug-dependent individuals could have important clinical implications for both women and men. © 2016 Wiley Periodicals, Inc.

OBJECTIVE The antioxidant N-acetylcysteine is being increasingly investigated as a therapeutic agent in the treatment of substance use disorders (SUDs). This study explored the efficacy of N-acetylcysteine in the treatment of posttraumatic stress disorder (PTSD), which frequently co-occurs with SUD and shares impaired prefrontal cortex regulation of basal ganglia circuitry, in particular at glutamate synapses in the nucleus accumbens. METHODS Veterans with PTSD and SUD per DSM-IV criteria (N = 35) were randomly assigned to receive a double-blind, 8-week course of N-acetylcysteine (2,400 mg/d) or placebo plus cognitive-behavioral therapy for SUD (between March 2013 and April 2014). Primary outcome measures included PTSD symptoms (Clinician-Administered PTSD Scale, PTSD Checklist-Military) and craving (Visual Analog Scale). Substance use and depression were also assessed. RESULTS Participants treated with N-acetylcysteine compared to placebo evidenced significant improvements in PTSD symptoms, craving, and depression (β values < -0.33; P values < .05). Substance use was low for both groups, and no significant between-group differences were observed. N-acetylcysteine was well tolerated, and retention was high. CONCLUSIONS This is the first randomized controlled trial to investigate N-acetylcysteine as a pharmacologic treatment for PTSD and SUD. Although preliminary, the findings provide initial support for the use of N-acetylcysteine in combination with psychotherapy among individuals with co-occurring PTSD and SUD. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02499029.

Background: Cocaine users often report a loss of arousal for nondrug-related stimuli, which may contribute to their response to drug-related rewards. However, little is known about users’ neural reactivity to emotional nondrug-related stimuli and the potential influence of gender. Objectives: Test the hypotheses that cocaine-dependent individuals have an attenuated neural response to arousing stimuli relative to controls and that this difference is amplified in women. Methods: The brain response to typically arousing positive and negative images as well as neutral images from the International Affective Picture System was measured in 40 individuals (20 non-treatment seeking cocaine-dependent and 20 age- and gender-matched control participants; 50% of whom were women). Images were displayed for 4 s each in blocks of five across two 270-second runs. General linear models assessed within and between group activation differences for the emotional images. Results: Cocaine-dependent individuals had a significantly lower response to typically arousing positive and negative images than controls, with attenuated neural activity present in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). Analyses by gender revealed less mPFC/ACC activation among female users, but not males, for both positive and negative images. Conclusion: The dampened neural response to typically arousing stimuli among cocaine-dependent polydrug users suggests decreased salience processing for nondrug stimuli, particularly among female users. This decreased responding is consistent with data from other substance using populations and suggests that this may be a general feature of addiction. Amplifying the neural response to naturally arousing nondrug-related reinforcers may present an opportunity for unique behavioral and brain stimulation therapies.

Background Despite increased attention to dentists’ roles in curbing opioid misuse, abuse, and diversion, information regarding prescribing practices and the frequency of multiple concurrent opioid prescriptions among dental patients is limited. Methods The authors reviewed South Carolina prescription drug monitoring program data representing dispensed medication for patients prescribed at least 1 opioid by a dentist during the most recently available 2-year time frame (2012-2013). The authors used descriptive analyses to examine the types and frequency of dental opioid prescriptions and the frequency of existing multiple concurrent opioid prescriptions among dental patients. Results Nearly all dispensed dental opioid prescriptions (99.9%; n = 653,650) were for immediate-release opioids and were initial prescription fills (96.2%). Hydrocodone (76.1%) and oxycodone (12.2%) combination products were the most frequently dispensed opioids prescribed by dentists. People younger than 21 years received 11.2% of dentist-prescribed opioids dispensed. Patients with multiple concurrent opioid prescriptions were identified within 30-day (n = 113,818), 90-day (n = 166,124), and 180-day (n = 205,576) time frames. Conclusions Dentists prescribed a high volume of the immediate-release opioids dispensed in South Carolina. A notable minority of dental patients had incidents of multiple preexisting opioid prescriptions, a factor implicated in patient misuse, abuse, overdose, and diversion. Practical Implications Use of a prescription drug monitoring program before prescribing provides a record of controlled substances dispensed to a patient and may inform prescribing, coordination of care, and addiction screening or referral. Patients should receive information regarding misuse behaviors and their risks, as well as the importance of secure storage and disposal of leftover opioid medications.

Deficits in executive function have been associated with risk for relapse. Data from previous studies suggest that relapse may be triggered by stress and drug-paired cues and that there are significant sex differences in the magnitude of these responses. The aim of this study was to examine the impact of the pharmacological stressor and alpha-2 adrenergic receptor antagonist yohimbine and cocaine cues on executive function in cocaine-dependent men and women.In a double-blind placebo controlled cross-over study, cocaine-dependent men (n=12), cocaine-dependent women (n=27), control men (n=31) and control women (n=25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Participants performed the Connors' Continuous Performance Test II prior to medication/placebo administration and immediately after each cue exposure sessionHealthy controls had a significant increase in commission errors under the yohimbine condition [RR (95% CI)=1.1 (1.0-1.3), χ(2)1=2.0, p=0.050]. Cocaine-dependent individuals exhibited a significant decrease in omission errors under the yohimbine condition [RR (95% CI)=0.6 (0.4-0.8), χ(2)1=8.6, p=0.003]. Cocaine-dependent women had more omission errors as compared to cocaine-dependent men regardless of treatment [RR (95% CI)=7.2 (3.6-14.7), χ(2)1=30.1, p0.001]. Cocaine-dependent women exhibited a slower hit reaction time as compared to cocaine-dependent men [Female 354 ± 13 vs. Male 415 ± 14; t89=2.6, p=0.012].These data add to a growing literature demonstrating significant sex differences in behaviors associated with relapse in cocaine-dependent individuals.

Objective Maternal stress in humans influences behavior of children and can be assessed using biological markers. Mothers and their one-month-old infants were recruited from an existing study to examine baseline maternal serum oxytocin and hypothalamic-pituitary-adrenal axis response to infant blood heel stick stress as measured by salivary cortisol in the dyads. Objectives were to explore (1) relationships between mother and infant cortisol levels, (2) gender differences in infant biologic cortisol response, and (3) the association of cortisol levels in the dyads and maternal oxytocin levels Methods Forty-two mother–infant dyads provided biologic samples and self-report data. Maternal oxytocin samples were obtained. Initial salivary cortisol was assessed in both the mother and infant, followed by a heel stick blood draw. Twenty minutes later, salivary cortisol was collected again from dyads. Results Self-report measures were negative for depression and risk for childhood neglect. Although oxytocin and baseline cortisol in the infants was higher in mothers that did some breast-feeding, there was no statistically significant difference ( p = 0.2 and p = 0.1, respectively). Analyses showed (a) higher baseline cortisol in mothers was related to higher baseline cortisol in infants ( p ≤ 0.0001), (b) following the stressor, female infants had a larger positive change in cortisol, after adjusting for baseline cortisol ( p = 0.045), and (c) there was no relationship between dyad cortisol levels and maternal oxytocin. Conclusions Maternal and infant biologic stress measures are related. Female infants have a larger hypothalamic-pituitary-adrenal response to a blood draw stressor as measured by salivary cortisol than male infants.

PURPOSE: This study compared rural to non-rural dentists with respect to opioid prescribing practices, perceptions about prescription drug abuse among patients, and training relevant to pain management and addictions. METHODS: A web-based, cross-sectional questionnaire was administered to practicing dentist members of the National Dental Practice-Based Research Network (PBRN; N=822) and linked with Network Enrollment Questionnaire data regarding practitioner demographics and practice characteristics. Pain management prescribing practices and perceptions regarding relevance and scope of addiction and drug diversion among patients were assessed. Rural practice was defined as a practice whose ZIP Code has more than 50% of its population in either a nonmetropolitan county and/or a rural Census tract. FINDINGS: Rural dentists were significantly more likely than their non-rural counterparts to recommend non-steroidal anti-inflammatory agents/acetaminophen in combination with prescribing an opioid [F (1,820) = 4.59, P = .03]. Compared to non-rural dentists, rural dentists were more likely to report that opioid abuse/diversion was a problem in their practices [χ(2) [1, n=807] = 6.85, P < .001], were more likely to have suspected a patient of abuse or diversion [χ(2) [1, n=807] = 10.12, P = .001], and were more likely to have refrained from prescribing due to suspicions of abuse or diversion [χ(2) [1, n=807] = 12.49, P < .001]. CONCLUSION: Rural dentists may be disproportionately impacted by patients’ opioid abuse and represent a viable target for educational outreach that encourages screening, identification, and referral of patients in need of drug abuse treatment.

To stimulate the formation of new cross-disciplinary translational research team collaborations and innovative pilot projects, the Medical University of South Carolina’s (MUSC) CTSA—South Carolina Clinical & Translational Research (SCTR) Institute—has initiated biannual scientific retreats often with speed dating style networking sessions. The themes of the retreats are cross-disciplinary, address unmet medical needs in South Carolina (SC) and beyond, stimulate formation of new cross-disciplinary teams, and are anticipated to generate pilot project and extramural grant applications related to novel translational research discoveries, technologies, and methodologies. The retreat format is designed to stimulate new research ideas and exchange in small groups to develop new research projects. The retreats are complemented by the SCTR Institute Pilot Project Program funds to support innovative pilot projects that emanate from the retreats. This chapter describes the design of the retreats, scientific impacts such as novel scientific collaborations and projects that the retreats have stimulated, challenges, and strategies for success.

Women with cocaine use disorder have worse treatment outcomes compared with men. Sex differences in cocaine addiction may be driven by differences in neurobiology or stress reactivity. Oxytocin is a potential therapeutic for stress reduction in substance use disorders, but no studies have examined the effect of oxytocin on neural response to drug cues in individuals with cocaine use disorders or potential sex differences in this response. The goal of this study was to examine the effect of intranasal oxytocin on cocaine cue reactivity in cocaine dependence, modulated by gender and history of childhood trauma. Cocaine-dependent men with (n = 24) or without (n = 19) a history of childhood trauma and cocaine-dependent women with (n = 16) or without (n = 8) a history of childhood trauma completed an fMRI cocaine cue reactivity task under intranasal placebo or oxytocin (40 IU) on two different days. fMRI response was measured in the right amygdala and dorsomedial prefrontal cortex (DMPFC). In the DMPFC, oxytocin reduced fMRI response to cocaine cues across all subject groups. However, in the amygdala, only men with a history of childhood trauma showed a significantly reduced fMRI response to cocaine cues on oxytocin versus placebo, while women with a history of childhood trauma showed an enhanced amygdala response to cocaine cues following oxytocin administration. Cocaine-dependent subjects with no history of childhood trauma showed no effect of oxytocin on amygdala response. Oxytocin can reduce cue reactivity in cocaine dependence, but its effect is modified by sex and childhood trauma history. Whereas men with cocaine dependence may benefit from oxytocin administration, additional studies are needed to determine whether oxytocin can be an effective therapeutic for cocaine-dependent women.