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BACKGROUND: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders and engagement in risky substance use behaviors. Women are overrepresented among individuals with more severe childhood adversity (≥4 types of ACEs) and may be at particular risk for aberrant substance use. OBJECTIVES: To assess the prevalence of ACEs among men and women with cannabis, opioid, cocaine, and tobacco use disorders. METHODS: Non-treatment-seeking individuals participating in clinical addiction research at a single site completed the ACE questionnaire and provided a detailed substance use history. Data were analyzed using proportional odds models and logistic regression. RESULTS: Most participants (424/565; 75%) reported at least one ACE, and more than one-quarter (156/565; 27%) reported severe childhood adversity. Relative to men (n=283), women (n=282) reported more ACEs (OR=1.49; p=0.01) and more experiences of emotional/physical abuse (OR=1.52; p=0.02), sexual abuse (OR=4.08; p=0.04), and neglect (OR=2.30; p

OBJECTIVE: To increase the number of physician-scientists in research, the Drug Abuse Research Training (DART) program at the Medical University of South Carolina offers a 2-year research track for psychiatry residents and a 10-week summer fellowship for students. The goal of this study was to examine program outcomes and alumni diversity levels over DART’s 15-year history. METHODS: To date, 215 trainees (44 residents, 171 summer fellows) have completed the program. An anonymous online survey was sent to the 143 program alumni with valid contact information. Survey data included demographic characteristics, post-program research involvement, and self-reported barriers to continued research engagement. RESULTS: Overall survey completion response was 83.5% (N = 122). The alumni included 59.0% women, and 36.1% of respondents identified as a member of a minority racial/ethnic group. Following program completion, 77.0% of the alumni reported continued research involvement. More than half of the alumni reported scientific publications (57.4%) and conference presentations (63.1%) since completing DART. Among respondents who did not subsequently engage in research, the most common modifiable barriers included difficulty finding a mentor, self-perceived deficits in statistical skills and research methodology, and overall lack of confidence in research ability. CONCLUSIONS: Over the past 15 years, the DART program has established a diverse research training program that now spans the educational spectrum from undergraduate to residency training. Future program goals include additional training to address self-reported modifiable research barriers. This program provides a model for other training programs designed to cultivate research interests and promote the diversity of clinical researchers.

Post-traumatic stress disorder (PTSD) and substance use disorder (SUD) occur frequently as comorbid diagnoses among adolescents. Historically, these conditions have been treated using a sequential model; however, emerging evidence suggests that an integrated treatment model may be most effective. This article presents two de-identified clinical case studies from an ongoing randomised controlled trial examining the efficacy of an integrated, exposure-based, cognitive-behavioral psychotherapy (CBT) for PTSD and SUD among adolescents (COPE-A), relative to a supportive counselling control condition (person-centred therapy). In both case studies, participants were randomised to receive the COPE-A integrated treatment, which incorporates prolonged exposure (PE) including imaginal and in vivo exposure as a core treatment component alongside CBT for PTSD and SUD. The clinical profile and treatment response of each participant is discussed. Promising results were found in both cases, with substantially reduced traumatic stress symptoms and decreased or stable levels of substance use by the end of treatment. Clinical implications of these early findings are discussed.

Background: Research is needed to improve understanding of work-life integration issues in academic medicine and to guide the implementation of the Doris Duke Charitable Foundation's Fund to Retain Clinical Scientists (FRCS), a national initiative offering financial support to physician-scientists facing caregiving challenges. Materials and Methods: In 2018, as part of a prospective program evaluation, the authors conducted a qualitative study to examine FRCS program participants' initial impressions, solicit descriptions of their career and caregiving experiences, and inquire how such factors might influence their professional advancement. The authors invited all 33 awardees who had been granted FRCS funding in the first year of the program to participate in the study, of whom 28 agreed to complete an interview. Analysts evaluated de-identified transcripts and explicated the data using a thematic analysis approach. Results: While participants described aspects of a culture that harbor stigma against caregivers and impede satisfactory work-life integration, they also perceived an optimistic cultural shift taking place as a result of programs like the FRCS. Their comments indicated that the FRCS has the potential to influence culture if institutional leadership simultaneously fosters a community that validates individuals both as caregivers and as scientists. Conclusions: Insights garnered from this qualitative study suggest that there is a pressing need for institutional leaders to implement programs that can foster awareness and normalization of caregiving challenges. In addition to providing funding and other tangible resources, interventions should strive to reinforce a broader culture that affirms the presence of work-life integration challenges and openly embraces solutions.

RATIONALE: Cocaine use disorder (CUD) is associated with dysregulation of the hypothalamic-pituitary-adrenal axis, which plays a critical role in the human stress response. Men and women with CUD differ in reactivity to social stressors. The hypothalamic neuropeptide oxytocin is involved in anxiolytic and natural reward processes, and has shown therapeutic potential for addictive disorders and stress reduction. OBJECTIVES: To examine the impact of oxytocin (oxytocin (OXY) vs. placebo (PBO)) and gender (female (F) vs. male (M)) on response to a social stress task in individuals with CUD. To explore whether ovarian hormones moderate this stress response. METHODS: One hundred twelve adults with CUD were randomized to receive 40 IU intranasal oxytocin (n = 56) or matching placebo (n = 56). Forty minutes after drug administration, participants were exposed to a social stressor. Generalized linear mixed models were used to examine neuroendocrine (cortisol) and subjective (craving, stress) response at pre-stressor, stressor + 0, + 10, + 30, + 60 min. RESULTS: Gender moderated the effect of oxytocin on neuroendocrine response (p = 0.048); women receiving oxytocin (F + OXY) showed blunted cortisol response compared to the other three groups (F + PBO; M + OXY; M + PBO). There was a main effect of gender on subjective stress response; women reported greater stress following the stressor compared to men (p = 0.016). Oxytocin had no significant effect on craving or stress, and gender did not moderate the effect of oxytocin on either measure. Higher endogenous progesterone was associated with lower craving response in women (p = 0.033). CONCLUSIONS: Oxytocin may have differential effects in men and women with CUD. Women may be at greater risk for relapse in response to social stressors, but ovarian hormones may attenuate this effect.

Contains fulltext : 220219.pdf (Publisher’s version ) (Open Access) Introduction: As one of the major health problems in the present century, the COVID-19 pandemic affected all parts of the global communities and the health of substance users are potentially at a greater risk of harm. This global study has been designed and conducted by the International Society of Addiction Medicine Practice and Policy Interest Group (ISAM-PPIG) to understand better the health related issues of people with Substance Use Disorders (SUD) as well as responses of the relevant health care systems during the pandemic. Methods: This is a cross-sectional study using convenient sampling. The data gathering was carried out with two follow-up stages each two months apart through an online conducted survey prepared using Google platform. The survey started by emergence of COVID-19 as a pandemic in March 2020 and respondents were followed till September 2020 when most of the initial lockdowns by most countries are supposed to be reopened. Ethics and Dissemination: The study was approved by the ethics committee of University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. The results will be published in relevant peer reviewing journals and communicated with different international stakeholders. 8 p.

The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common following sexual assault and associated with more severe symptomology and increased likelihood of sexual revictimization. Integrated interventions aimed at reducing PTSD and AUD symptoms following recent sexual assault are needed and should address barriers to care and early treatment termination. The proposed study will test a novel, brief (5 to 7 sessions) intervention that integrates Written Exposure Therapy for PTSD and Cognitive Behavioral Therapy for AUD, and is initiated within the first six weeks post-assault. In Phase 1, qualitative analysis of content gathered during focus groups with treatment providers will be conducted to inform intervention development. In Phase 2, a proof-of-concept pilot study (n = 10) of the intervention, Substance Use Skills Training and Exposure Post-Sexual Assault (STEPS), will be conducted. In Phase 3, a pilot randomized controlled trial (RCT) among 54 recent sexual assault survivors will be implemented using the updated manualized STEPS intervention to evaluate feasibility and preliminary efficacy in reducing PTSD and AUD symptoms. Ecological momentary assessments will be used to assess daily alcohol use, craving, affect, intrusions and avoidance. The effects of STEPS on commonly associated symptoms (e.g., depression, substance use) will be examined. The proposed study has the potential to make a significant public health impact by advancing knowledge on the link between sexual assault and co-occurring PTSD and AUD and informing early intervention efforts for this high-risk population.

As the nation seeks to recruit and retain physician-scientists, gaps remain in understanding and addressing mitigatable challenges to the success of faculty from underrepresented minority (URM) backgrounds. The Doris Duke Charitable Foundation Fund to Retain Clinical Scientists program, implemented in 2015 at 10 academic medical centers in the United States, seeks to retain physician-scientists at risk of leaving science because of periods of extraordinary family caregiving needs, hardships that URM faculty-especially those who identify as female-are more likely to experience. At the annual Fund to Retain Clinical Scientists program directors conference in 2018, program directors-21% of whom identify as URM individuals and 13% as male-addressed issues that affect URM physician-scientists in particular. Key issues that threaten the retention of URM physician-scientists were identified through focused literature reviews; institutional environmental scans; and structured small- and large-group discussions with program directors, staff, and participants. These issues include bias and discrimination, personal wealth differential, the minority tax (i.e., service burdens placed on URM faculty who represent URM perspectives on committees and at conferences), lack of mentorship training, intersectionality and isolation, concerns about confirming stereotypes, and institutional-level factors. The authors present recommendations for how to create an environment in which URM physician-scientists can expect equitable opportunities to thrive, as institutions demonstrate proactive allyship and remove structural barriers to success. Recommendations include providing universal training to reduce interpersonal bias and discrimination, addressing the consequences of the personal wealth gap through financial counseling and benefits, measuring the service faculty members provide to the institution as advocates for URM faculty issues and compensating them appropriately, supporting URM faculty who wish to engage in national leadership programs, and sustaining institutional policies that address structural and interpersonal barriers to inclusive excellence.

The opioid crisis in the USA requires immediate action through clinical and translational research. Already built network infrastructure through funding by the National Institute on Drug Abuse (NIDA) and National Center for Advancing Translational Sciences (NCATS) provides a major advantage to implement opioid-focused research which together could address this crisis. NIDA supports training grants and clinical trial networks; NCATS funds the Clinical and Translational Science Award (CTSA) Program with over 50 NCATS academic research hubs for regional clinical and translational research. Together, there is unique capacity for clinical research, bioinformatics, data science, community engagement, regulatory science, institutional partnerships, training and career development, and other key translational elements. The CTSA hubs provide unprecedented and timely response to local, regional, and national health crises to address research gaps [Clinical and Translational Science Awards Program, Center for Leading Innovation and Collaboration, Synergy paper request for applications]. This paper describes opportunities for collaborative opioid research at CTSA hubs and NIDA–NCATS opportunities that build capacity for best practices as this crisis evolves. Results of a Landscape Survey (among 63 hubs) are provided with descriptions of best practices and ideas for collaborations, with research conducted by hubs also involved in premier NIDA initiatives. Such collaborations could provide a rapid response to the opioid epidemic while advancing science in multiple disciplinary areas.

Background:There is discontent and turnover among faculty at US academic health centers because of the challenges in balancing clinical, research, teaching, and work–life responsibilities in the current healthcare environment. One potential strategy to improve faculty satisfaction and limit turnover is through faculty mentoring programs.Methods:A Mentor Leadership Council was formed to design and implement an institution-wide faculty mentoring program across all colleges at an academic health center. The authors conducted an experimental study of the impact of the mentoring program using pre-intervention (2011) and 6-year (2017) post-intervention faculty surveys that measured the long-term effectiveness of the program.Results:The percent of faculty who responded to the surveys was 45.9% (656/1428) in 2011 and 40.2% (706/1756) in 2017. For faculty below the rank of full professor, percent of faculty with a mentor (45.3% vs. 67.1%, P < 0.001), familiarity with promotion criteria (81.7% vs. 90.0%, P = 0.001), and satisfaction with department’s support of career (75.6% vs. 84.7%, P = 0.002) improved. The percent of full professors serving as mentors also increased from 50.3% in 2011 to 68.0% in 2017 (P = 0.002). However, the percent of non-retiring faculty considering leaving the institution over the next 2 years increased from 18.8% in 2011 to 24.3% in 2017 (P = 0.02).Conclusions:Implementation of an institution-wide faculty mentoring program significantly improved metrics of career development and faculty satisfaction but was not associated with a reduction in the percent of faculty considering leaving the institution. This suggests the need for additional efforts to identify and limit factors driving faculty turnover.

Background The purpose of this study was to describe dentists’ training experiences relevant to pain management, addiction, and prescription opioid drug diversion and examine associations between these training experiences and dentists’ opioid prescribing practices. Methods A Web-based, cross-sectional survey was conducted among practicing dentist members of the National Dental Practice-Based Research Network (PBRN; N = 822). The survey assessed pain management prescribing practices and training experiences related to pain management and assessment for addiction and drug diversion. Survey data were linked with National Dental PBRN Enrollment Questionnaire data regarding practitioner demographics and practice characteristics. Results The majority of dentists (67%) reported prior training in pain management; however, a minority of dentists reported prior training regarding identification and assessment of drug abuse or addiction (48%) or identification of prescription drug diversion (25%). The majority of training experiences across all topics occurred through continuing dental education participation. Dental school training relevant to pain management, addiction, and identification of drug diversion was more prevalent among more recent dental school graduates. Training experiences were associated with prescribing practices. Conclusions Results suggest that across multiple levels of training, many dentists are not receiving training specific to addiction assessment and identification of drug diversion. Such training is associated with greater consistency of risk mitigation implementation in practice.

Although the United States is often ahead in both research and health care fields, it lags behind peer countries in many population health indicators. To address these complex health problems that often reflect the intersection of many socioeconomic and health issues, it is essential that scientists work collaboratively across distinct disciplines. Women's health is but one area which can benefit from such an approach given the multifaceted and complex issues underlying the different aspects of women's health research. The National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) and the Office of Women's Health of the U.S. Food and Drug Administration (FDA) cosponsored a preconference symposium at the Women's Health 2018 Conference, held in May in Arlington, VA, to highlight interdisciplinary approaches to research, how researchers can work collaboratively, and how to apply multifaceted approaches to complex real-world problems. Three speakers presented information on a range of subjects related to the health of women across the life course, including the distinction between multidisciplinary, interdisciplinary, and transdisciplinary approaches; the science behind Team Science and how its findings apply to working collaboratively; and gender inequalities in the opioid epidemic. This article summarizes the major points of the presentations and the subsequent discussions.

BACKGROUND: Opioid dependence is a significant public health problem in the United States and the number of opioid overdose deaths among women has increased dramatically in comparison to men in the last few years. In this context, understanding the biological mechanisms underlying gender differences in vulnerability to opioid dependence is essential. METHODS: The current pilot study examined gender differences in subjective stress, heart rate (HR), and cortisol/ dephydroepiandrosterone (DHEA) response to a laboratory stressor (Trier Social Stress Test; TSST) or a no-stress condition, and drug cue paradigm among men (n=21) and women (n=18) with opioid dependence. RESULTS: Significant group (TSST vs. no stress) differences emerged in self-reported stress [F(1,35)=41.77, p

The hypothalamic-pituitary-adrenal (HPA) axis is a critical hormonal system involved in stress response. A number of studies have investigated the HPA axis response of drug-dependent individuals to stressors. Stress-induced vulnerabilities in the HPA axis may differ in response to chronic use of different substances, possibly leading to different target therapies. There has not been a direct comparison of HPA axis and subjective response between individuals with different types of substance use disorders following a laboratory stress intervention.The primary goal of the current study was to compare subjective and neuroendocrine response to the Trier Social Stress Task (TSST) across multiple primary types of substance use disorders and investigate differential response between males and females.Four hundred participants were drawn from seven studies completed at the Medical University of South Carolina between 2011 and 2021. The TSST was utilized across studies and subjective and neuroendocrine responses measured following completion. Generalized linear mixed effects models and area under the response curve analysis were used to compare both substance type and sex differences.The study groups involving individuals with cocaine use disorder had blunted stress, craving and cortisol response following the TSST as compared to other substance use groups. Females in the cocaine groups reported higher subjective stress but lower cortisol than males.The study results indicate that there may be differential effects of substances on the HPA axis, with cocaine using individuals exhibiting more blunting of the HPA axis response as compared to users of other substances.

BACKGROUND Opioid use disorder (OUD) remains a public health crisis in the USA. Although stress and craving are common precipitants of substance use, no research to date has investigated the impact of laboratory-induced stress and craving on subsequent opioid use. METHOD Participants (N = 31) were individuals with prescription OUD who completed a human laboratory study followed by a one-month follow-up visit. Participants were randomly assigned to either a stress task (i.e., Trier Social Tress Task; TSST) or a no-stress condition, and then all participants completed an opioid cue paradigm. Measures of subjective (e.g., stress, craving), and neuroendocrine (e.g., cortisol, dehydroepiandrosterone) reactivity were assessed before and after each task. Survival and regression models tested the association between reactivity to the laboratory tasks and a) time to first opioid use and b) amount of opioid use during follow-up. RESULTS On average, participants first used opioids 3.65 (SD = 2.08) days following the study. Craving after the opioid cue paradigm (B = 0.44, Exp(B) = 1.55, 95 % CI [1.06, 2.28], p = .02) and after the TSST/no-stress condition plus opioid cue paradigm (B = 1.06, Exp(B) = 2.88, 95 % CI [1.70, 4.85], p < .001) predicted time to first use. Additionally, there was a significant interaction between randomization to the TSST, stress reactivity, and amount of opioids used. CONCLUSIONS Findings demonstrate that elevated cue-induced craving, either in the context of a stressor or not, is associated with shortened time to opioid use, whereas stress reactivity impacts the amount of opioids consumed. Preliminary findings add to the literature on stress, craving and opioid use and implicate treatment.

Opioid Use Disorders (OUDs) and drug overdose deaths are increasing at alarmingly high rates in the United States. Stress and dysregulation in biologic stress response systems such as the hypothalamic-pituitary-adrenal axis and noradrenergic system appear to play an important role in the pathophysiology of substance use disorders and relapse to drug use, particularly for women. Alpha-2 adrenergic agonist medications effectively decrease noradrenergic activity and have demonstrated benefit in preventing relapse to substance use and decreasing stress-reactivity and craving in cocaine- and nicotine-dependent women, compared to men. Alpha-2 adrenergic agonists may help decrease stress reactivity in individuals with OUDs and prevent relapse to drug use, but gender differences have yet to be systematically explored. We describe the rationale, study design and methodology of a randomized, double-blind, placebo-controlled clinical trial examining gender differences in stress, craving and drug use among adult men and women with OUD taking methadone or buprenorphine and randomly assigned to an alpha-2 adrenergic agonist, lofexidine, compared to placebo. In addition, we describe methods for measuring daily stress, craving and drug use in participant's natural environment as well as participant's physiological (i.e., heart rate, cortisol) and psychological (i.e., stress, craving) response to laboratory social and drug cue stressors. Lastly, we detail methods adopted to sustain research activity while following guidelines for the COVID-19 pandemic. ClinicalTrials.gov Registration Number: NCT03718065.

Novel treatments that target neurobiological alterations associated with childhood trauma, particularly among those with posttraumatic stress disorder (PTSD), could mitigate negative outcomes for these at-risk individuals. PTSD is characterized by abnormalities within the brain's salience network and reward circuitry, which are modulated by intranasal oxytocin. Using a double-blind, randomized, placebo-controlled crossover design, we tested whether intranasal oxytocin (24 international units) influenced functional coupling of the amygdala with the anterior insula (AI), dorsal anterior cingulate cortex, and nucleus accumbens in response to implicitly presented fearful, angry, and happy faces among childhood trauma-exposed individuals with (n = 16, 9 women) and without PTSD (n = 18, 12 women). Psychophysiological interaction analyses revealed that oxytocin effects were limited to amygdala-AI connectivity in the fear condition, distinct for men and women, and not impacted by PTSD diagnosis. In response to fear faces, oxytocin reduced left amygdala-left AI connectivity for women but not men; reduced left amygdala-right AI connectivity among women, but increased this connectivity in men; and reduced right amygdala-right anterior insula connectivity for men, but increased it for women. Results suggest that intranasal oxytocin modulates threat salience among childhood trauma-exposed individuals and that these effects vary as a function of gender and hemisphere.

Clinical trials are a fundamental tool in evaluating the safety and efficacy of new drugs, medical devices, and health system interventions. Clinical trial visits generally involve eligibility assessment, enrollment, intervention administration, data collection, and follow-up, with many of these steps performed during face-to-face visits between participants and the investigative team. Social distancing, which emerged as one of the mainstay strategies for reducing the spread of SARS-CoV-2, has presented a challenge to the traditional model of clinical trial conduct, causing many research teams to halt all in-person contacts except for life-saving research. Nonetheless, clinical research has continued during the pandemic because study teams adapted quickly, turning to virtual visits and other similar methods to complete critical research activities. The purpose of this special communication is to document this rapid transition to virtual methodologies at Clinical and Translational Science Awards hubs and highlight important considerations for future development. Looking beyond the pandemic, we envision that a hybrid approach, which implements remote activities when feasible but also maintains in-person activities as necessary, will be adopted more widely for clinical trials. There will always be a need for in-person aspects of clinical research, but future study designs will need to incorporate remote capabilities.

Mindfulness based interventions have been shown to be efficacious in treating depression, anxiety, pain and substance use disorders (SUDs). Mindfulness-Based Relapse Prevention (MBRP) is an intervention that integrates cognitive-behavioral relapse prevention and mindfulness meditation practices, in an 8-week, manualized group intervention designed to treat SUDs by helping patients regulate negative emotional states and reactive behavior. This paper describes the rationale, study design and methodology of a two-site, randomized controlled trial comparing MBRP to 12-Step Facilitation (TSF) in military Veterans following completion of intensive outpatient treatment for SUDs. The 8 weeks of 90-min, group-based MBRP or TSF sessions are followed by 3-, 6- and 10-month follow-up period with assessments of alcohol/drug use, quality of life, depression, anxiety, mindfulness and other functional outcomes, such as employment. The primary hypothesis is that MBRP will be significantly better than TSF in promoting recovery and prevention of relapse to substance use in a military Veteran population. The secondary hypothesis is that MBRP will lead to greater improvements in quality of life, depression/anxiety, and functional outcomes, such as employment. This study is designed to provide information about the use of group-based MBRP as a relapse prevention strategy for military Veterans who have completed an intensive SUD clinical treatment program. Clinical Trial Identifier: NCT02326363