Differential prevalence of Adverse Childhood Experiences (ACEs) by gender and substance used in individuals with cannabis, cocaine, opioid, and tobacco use disorders.

Background: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders (SUDs) 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 = .01) and more experiences of emotional/physical abuse (OR = 1.52; p = .02), sexual abuse (OR = 4.08; p = .04), and neglect (OR = 2.30; p < .01). Participants in the cocaine (OR = 1.87; n = .01) and opioid (OR = 2.21; p = .01) use disorder, but not cannabis use disorder (OR = 1.46; p = .08), studies reported more severe adversity relative to the tobacco group. Relative to tobacco users, emotional/physical abuse (OR = 1.92; p = .02) and neglect (OR = 2.46; p = .01) scores were higher in cocaine users and household dysfunction scores were higher in opioid users (OR = 2.67; p = .01).Conclusion: The prevalence of ACEs differs with respect to both participant gender and primary substance used. Novel SUD treatment strategies that incorporate ACEs may be uniquely beneficial in specific subpopulations of people with SUDs.

Trends in Self-Reported Fentanyl and Other Illicit Substance Use in South Carolina Emergency Department Patients, 2020-2022.

BACKGROUND: Opioid-involved deaths are continuing to increase across the United States, exceeding 100,000 for the first time in 2021. Contamination with, and intentional use of, synthetic opioids such as fentanyl are a major driver of this increase. Utilizing self-report substance use data of patients being treated in the emergency department (ED) can be useful to determine which substances patients are intentionally seeking. OBJECTIVES: 1) Examine changes in self-reported illicit substance use (including fentanyl) over time; 2) Examine changes in the co-occurrence of self-reported fentanyl with other illicit substance use over time. METHODS: All patients presenting to the study EDs that answered anything other than "never" on the National Institute on Drug Abuse Quick Screen and were seen by a peer recovery specialist in the ED between July 1, 2020 and December 31, 2022 were included for analysis. The substance of use as reported by each patient was recorded by the peer recovery specialist. Differences in substance use by type over time were examined using chi-squared tests of proportions. RESULTS: There were 7568 patients that met inclusion criteria. Self-reported fentanyl (1760%; p < 0.0001) and cocaine (82%; p = 0.034) use increased, whereas heroin use (16%; p < 0.0001) decreased. CONCLUSIONS: Self-reported fentanyl and cocaine use has increased significantly in South Carolina ED patients between 2020 and 2022. Given the high morbidity and mortality associated with fentanyl and fentanyl analog use, further measures to identify these patients and provide harm reduction and treatment from the ED setting are warranted.

The Drug Abuse Research Training (DART) Program for Psychiatry Residents and Summer Fellows: 15-Year Outcomes.

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.

Retention in Treatment after Emergency Department-Initiated Buprenorphine.

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.

Rates of substance use disorder treatment seeking visits after emergency department-initiated buprenorphine.

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.

Does trauma-focused exposure therapy exacerbate symptoms among patients with comorbid PTSD and substance use disorders?

BACKGROUND: Although exposure-based therapy is a well-established, effective treatment for post-traumatic stress disorder (PTSD), some practitioners report reluctance to implement it due to concerns that it may exacerbate symptoms of PTSD and commonly comorbid disorders, such as substance use disorders (SUD). AIM: This study compared the exacerbation of psychological symptoms among participants with comorbid PTSD and SUD who received either SUD treatment alone or SUD treatment integrated with exposure therapy for PTSD. METHOD: Participants (N = 71) were treatment-seeking, military Veterans with comorbid PTSD and SUD who were randomized to 12 individual sessions of either (1) an integrated, exposure-based treatment (Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure; COPE); or (2) a non-exposure-based, SUD-only treatment (Relapse Prevention; RP). We examined between-group differences in the frequency of statistically reliable exacerbations of PTSD, SUD and depression symptoms experienced during treatment. RESULTS: At each of the 12 sessions, symptom exacerbation was minimal and generally equally likely in either treatment group. However, an analysis of treatment completers suggests that RP participants experienced slightly more exacerbations of PTSD symptoms during the course of treatment. CONCLUSIONS: This study is the first to investigate symptom exacerbation throughout trauma-focused exposure therapy for individuals with comorbid PTSD and SUD. Results add to a growing literature which suggests that trauma-focused, exposure-based therapy does not increase the risk of symptom exacerbation relative to non-exposure-based therapy.

Training experiences regarding pain management, addiction, and drug diversion of dentists enrolled in the National Dental Practice-Based Research Network.

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.

Heterogeneity of treatment dropout: PTSD, depression, and alcohol use disorder reductions in PTSD and AUD/SUD treatment noncompleters.

Treatment dropout is often assumed to be due to worsening or lack of symptom improvement, despite minimal research examining symptom change among treatment dropouts. Thus, the present study examined symptom change in veterans who discontinued evidence-based treatment for comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Participants were veterans who completed at least one session of a 12-session Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE) for comorbid PTSD/AUD. The study analyses investigated the 43% of the sample (n = 22) that did not complete the full 12-session protocol and were therefore considered treatment dropouts. Symptom changes in PTSD, AUD, and depression were examined among dropouts using two methods: (a) clinically significant change criteria and (b) good end-state criteria. Results indicated that a significant proportion of treatment dropouts displayed clinically significant improvement and/or met good end-state criteria for PTSD (40-59%), AUD (66%), and depression (45-68%) prior to dropping out. The results revealed that participants who displayed symptom improvement attended more treatment sessions and completed more imaginal exposures than participants who did not experience significant improvement. Together, the findings add to a growing body of literature suggesting that a large proportion of treatment dropouts may actually improve. Although preliminary, the findings challenge the notion that treatment dropout is always associated with negative outcomes.

Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study.

Background: The goal of this study was to conduct a preliminary network analysis (using graph-theory measures) of intrinsic functional connectivity in adult smokers, with an exploration of sex differences in smokers. Methods: Twenty-seven adult smokers (13 males; mean age = 35) and 17 sex and age-matched controls (11 males; mean age = 35) completed a blood oxygen level-dependent resting state functional magnetic resonance imaging experiment. Data analysis involved preprocessing, creation of connectivity matrices using partial correlation, and computation of graph-theory measures using the Brain Connectivity Toolbox. Connector hubs and additional graph-theory measures were examined for differences between smokers and controls and correlations with nicotine dependence. Sex differences were examined in a priori regions of interest based on prior literature. Results: Compared to nonsmokers, connector hubs in smokers emerged primarily in limbic (parahippocampus) and salience network (cingulate cortex) regions. In addition, global influence of the right insula and left nucleus accumbens was associated with higher nicotine dependence. These trends were present in male but not female smokers. Conclusions: Network communication was altered in smokers, primarily in limbic and salience network regions. Network topology was associated with nicotine dependence in male but not female smokers in regions associated with reinforcement (nucleus accumbens) and craving (insula), consistent with the idea that male smokers are more sensitive to the reinforcing aspects of nicotine than female smokers. Implications: Identifying alterations in brain network communication in male and female smokers can help tailor future behavioral and pharmacological smoking interventions. Male smokers showed alterations in brain networks associated with the reinforcing effects of nicotine more so than females, suggesting that pharmacotherapies targeting reinforcement and craving may be more efficacious in male smokers.

Impact of gender on corticotropin-releasing factor and noradrenergic sensitivity in cocaine use disorder.

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.

Individualized real-time fMRI neurofeedback to attenuate craving in nicotine-dependent smokers.

BACKGROUND: Cue-induced craving plays an important role in relapse, and the neural correlates of cue-induced craving have been elucidated using fMRI. This study examined the utility of real-time fMRI (rtfMRI) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers. METHODS: Nicotine-dependent smokers were randomized to rtfMRI neurofeedback or to a no-feedback control group. Participants completed 3 neuroimaging visits. Within each visit, an initial run during which smoking-related cues were used to provoke craving, an individualized craving-related region of interest (ROI) in the prefrontal cortex or anterior cingulate cortex was identified. In the rtfMRI group, activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure. The control group had an identical experience with no feedback provided. RESULTS: Forty-four nicotine-dependent smokers were recruited to participate in our study; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis. Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group. LIMITATIONS: As participants were not seeking treatment, clinical outcomes are lacking. CONCLUSION: Nicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue-elicited neural activation and craving, relative to a control group. Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinically meaningful treatment modality.

IRB reliance: An informatics approach.

Multi-site Institutional Review Board (IRB) review of clinical research projects is an important but complex and time-consuming activity that is hampered by disparate non-interoperable computer systems for management of IRB applications. This paper describes our work toward harmonizing the workflow and data model of IRB applications through the development of a software-as-a-service shared-IRB platform for five institutions in South Carolina. Several commonalities and differences were recognized across institutions and a core data model that included the data elements necessary for IRB applications across all institutions was identified. We extended and modified the system to support collaborative reviews of IRB proposals within routine workflows of participating IRBs. Overall about 80% of IRB application content was harmonized across all institutions, establishing the foundation for a streamlined cooperative review and reliance. Since going live in 2011, 49 applications that underwent cooperative reviews over a three year period were approved, with the majority involving 2 out of 5 institutions. We believe this effort will inform future work on a common IRB data model that will allow interoperability through a federated approach for sharing IRB reviews and decisions with the goal of promoting reliance across institutions in the translational research community at large.

Lower subcortical gray matter volume in both younger smokers and established smokers relative to non-smokers.

Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non-smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error-corrected clusters, P < 0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre-existing differences in these areas may predispose individuals to the development of nicotine dependence.

Attenuated neural response to emotional cues in cocaine-dependence: a preliminary analysis of gender differences.

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.

Dental opioid prescribing practices and risk mitigation strategy implementation: Identification of potential targets for provider-level intervention.

BACKGROUND: Given the regular use of immediate-release opioids for dental pain management, as well as documented opioid misuse among dental patients, the dental visit may provide a viable point of intervention to screen, identify, and educate patients regarding the risks associated with prescription opioid misuse and diversion. The aims of this statewide survey of dental practitioners were to assess (a) awareness of the scope of prescription opioid misuse and diversion; (b) current opioid prescribing practices; (c) use of and opinions regarding risk mitigation strategies; and (d) use and perceived utility of drug monitoring programs. METHODS: This cross-sectional study surveyed dentists (N = 87) participating in statewide professional and alumni organizations. Dentists were invited via e-mail and listserv announcement to participate in a one-time, online, 59-item, self-administered survey. RESULTS: A majority of respondents reported prescribing opioids (n = 66; 75.8%). A minority of respondents (n = 38; 44%) reported regularly screening for current prescription drug abuse. Dentists reported low rates of requesting prior medical records (n = 5; 5.8%). Only 38% (n = 33) of respondents had ever accessed a prescription drug monitoring program (PDMP), and only 4 (4.7%) consistently used a PDMP. Dentists reporting prior training in drug diversion were significantly more likely to have accessed their PDMP, P < .01. Interest in continuing education regarding assessment of prescription drug abuse/diversion and use of drug monitoring programs was high. CONCLUSIONS: Although most dentists received training related to prescribing opioids, findings identified a gap in existing dental training in the assessment/identification of prescription opioid misuse and diversion. Findings also identified gaps in the implementation of recommended risk mitigation strategies, including screening for prescription drug abuse, consistent provision of patient education, and use of a PDMP prior to prescribing opioids.

Biologic effects of stress and bonding in mother-infant pairs.

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.

Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers.

The insula has been implicated in cue-induced craving and relapse in nicotine-dependent tobacco cigarette smokers. The aims of the present study were to identify brain regions that exhibit greater functional connectivity with the right anterior insula in response to smoking cues than to neutral cues and the role of functional connectivity between these regions in mediating cue-induced craving in healthy (free of axis I psychiatric disorders) nicotine-dependent tobacco cigarette smokers. Functional magnetic resonance imaging data were collected from 63 healthy nicotine-dependent smokers viewing blocks of smoking and neutral cues. Craving ratings were obtained after each block. A psychophysiologic interaction approach was used to identify regions that exhibited significantly greater functional connectivity with the right anterior insula (seed) during the smoking cues than during the neutral (corrected cluster thresholding, Z > 2.3, P = 0.05). Parameter estimates of the interaction effects from each region were regressed against the mean cue-induced craving scores. Significant task by seed interactions were observed in two clusters centered in the bilateral precuneus and left angular gyrus. The strength of connectivity between the right anterior insula and the precuneus, which is involved interoceptive processing and self-awareness, was positively correlated with the magnitude of the craving response to the smoking cues (r(2) = 0.15; P < 0.01). These data suggest that among smokers, cue-induced craving may be a function of connectivity between two regions involved in interoception and self-awareness. Moreover, treatment strategies that incorporate mindful attention may be effective in attenuating cue-induced craving and relapse in nicotine-dependent smokers.

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence.

BACKGROUND: Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. METHODS: In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. RESULTS: DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. CONCLUSIONS: 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. SCIENTIFIC SIGNIFICANCE: Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity.

Impact of acute guanfacine administration on stress and cue reactivity in cocaine-dependent individuals.

BACKGROUND: Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals. Thus, medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine-dependent individuals. OBJECTIVES: To examine the impact of acute administration of the α2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. METHODS: In a double-blind, placebo-controlled study, cocaine-dependent individuals (n = 84), were randomized to receive either 2 mg guanfacine (n = 50) or placebo (n = 34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n = 26; placebo n = 15) or a no-stress (guanfacine n = 24; placebo n = 19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. RESULTS: The no-stress guanfacine group reported greater craving in response to cocaine cues as compared to the neutral cue (p < 0.001). The guanfacine stress group reported greater subjective stress at the neutral cue than at baseline (p = 0.032). The cocaine cue increased subjective stress in the guanfacine (p < 0.001) no-stress group. There were no effects of guanfacine on cortisol levels in either the stress or no stress groups (all p > 0.70). CONCLUSION: This study found no effects of a single 2 mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2 mg dose of guanfacine may not be an effective therapeutic treatment strategy.