Cocaine-dependent Subjects Research Articles

Executive control network resting state fMRI functional and effective connectivity and delay discounting in cocaine dependent subjects compared to healthy controls.

Resting state functional magnetic resonance imaging (fMRI) has been used to study functional connectivity of brain networks in addictions. However, most studies to-date have focused on the default mode network (DMN) with fewer studies assessing the executive control network (ECN) and salience network (SN), despite well-documented cognitive executive behavioral deficits in addictions. The present study assessed the functional and effective connectivity of the ECN, DMN, and SN in cocaine dependent subjects (CD) (n = 22) compared to healthy control subjects (HC) (n = 22) matched on age and education. This study also investigated the relationship between impulsivity measured by delay discounting and functional and effective connectivity of the ECN, DMN, and SN. The Left ECN (LECN), Right ECN (RECN), DMN, and SN functional networks were identified using FSL MELODIC independent component analysis. Functional connectivity differences between CD and HC were assessed using FSL Dual Regression analysis and FSLNets. Effective connectivity differences between CD and HC were measured using the Parametric Empirical Bayes module of Dynamic Causal Modeling. The relationship between delay discounting and functional and effective connectivity were examined using regression analyses. Dynamic causal modeling (DCM) analysis showed strong evidence (posterior probability > 0.95) for CD to have greater effective connectivity than HC in the RECN to LECN pathway when tobacco use was included as a factor in the model. DCM analysis showed strong evidence for a positive association between delay discounting and effective connectivity for the RECN to LECN pathway and for the DMN to DMN self-connection. There was strong evidence for a negative association between delay discounting and effective connectivity for the DMN to RECN pathway and for the SN to DMN pathway. Results also showed strong evidence for a negative association between delay discounting and effective connectivity for the RECN to SN pathway in CD but a positive association in HC. These novel findings provide preliminary support that RECN effective connectivity may differ between CD and HC after controlling for tobacco use. RECN effective connectivity may also relate to tobacco use and impulsivity as measured by delay discounting.

Midcingulate Cortical Activations Interrelate Chronic Craving and Physiological Responses to Negative Emotions in Cocaine Addiction

BackgroundNegative emotions precipitate drug craving. Individuals vary in how they engage in negative emotions, as may be reflected in physiological arousal elicited by the emotions. It remains unclear whether physiological responses to negative emotions relate to cocaine craving and how regional brain activations support this relationship. MethodsWe examined brain activation and skin conductance responses (SCRs) among 40 cocaine-dependent (CD) subjects and 37 healthy control subjects during exposure to negative-emotional and neutral images. Imaging and SCR data were processed with published routines, and the results were evaluated at a corrected threshold. ResultsRelative to control subjects, CD subjects showed increased activation in the hippocampus, inferior parietal gyrus, and caudate in response to negative-emotional versus neutral images. CD subjects relative to control subjects showed diminished SCR to negative-emotional versus neutral images, and the difference (SCRNE-NU) was positively correlated with chronic craving, as evaluated by the Cocaine Craving Questionnaire, and craving rating (negative-emotional – neutral), in CD subjects. Activations of the midcingulate cortex (MCC) were positively correlated with both chronic cocaine craving and SCRNE-NU and completely mediated the correlation between chronic cocaine craving and SCRNE-NU. Further, path analyses suggested a directional influence of SCRNE-NU on craving rating (negative-emotional – neutral): chronic craving → MCC activation → SCRNE-NU → craving rating. ConclusionsCD subjects demonstrate hypoactive SCRs to negative emotions. Less diminution of SCR is associated with higher cocaine craving and MCC response to negative emotions. A hub of the limbic motor circuit, the MCC may translate chronic cocaine craving into physiological responses that precipitate cocaine seeking.

Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study.

Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Assessment of cortisol in saliva has emerged as a reliable way of evaluating HPA function. We examined the relationships between salivary cortisol levels with both craving and cognitive performance, as a possible biomarker of cocaine addiction. Cognitive performance (attention, declarative and working memory, executive functions and recognition of emotions) was assessed in 14 abstinent cocaine-dependent subjects in outpatient treatment and 13 control participants. Three salivary samples were collected at home by all the participants in the morning, afternoon and at bedtime. Patients showed higher levels of cortisol in the morning, as well as higher area under the curve with respect to the ground (AUCg). Regarding cognitive performance, cocaine-abstinent subjects showed worse performance in attention (d2 test), verbal memory (Spanish Complementary Verbal Learning Test, TAVEC) and executive tests (Tower of Hanoi and phonological fluency test) with respect to the control group. Morning cortisol levels and the AUCg index were negatively associated with the age of onset of drug consumption and the AUCg index was also positively associated with craving in our patients’ group. Moreover, morning cortisol levels, as well as the AUCg index, were negatively associated with verbal memory performance. Therefore, our pilot study suggests that salivary cortisol measurements could be a good avenue to predict craving level, as well as cognitive status, especially the declarative memory domain.

Exploring allele specific methylation in drug dependence susceptibility

Drug dependence is a neuropsychiatric condition that involves genetic, epigenetic and environmental factors. Allele-specific methylation (ASM) is a common and stable epigenetic mechanism that involves genetic variants correlating with differential levels of methylation at CpG sites. We selected 182 single-nucleotide polymorphisms (SNPs) described to influence cis ASM in human brain regions to evaluate their possible contribution to drug dependence susceptibility. We performed a case-control association study in a discovery sample of 578 drug-dependent patients (including 428 cocaine-dependent subjects) and 656 controls from Spain, and then, we followed-up the significant associations in an independent sample of 1119 cases (including 589 cocaine-dependent subjects) and 1092 controls. In the discovery sample, we identified five nominal associations, one of them replicated in the follow-up sample (rs6020251). The pooled analysis revealed an association between drug dependence and rs6020251 but also rs11585570, both overcoming the Bonferroni correction for multiple testing. We performed the same analysis considering only cocaine-dependent patients and obtained similar results. The rs6020251 variant correlates with differential methylation levels of cg17974185 and lies in the first intron of the CTNNBL1 gene, in a genomic region with multiple histone marks related to enhancer and promoter regions in brain. Rs11585570 is an eQTL in brain and blood for the SCP2 and ECHDC2 genes and correlates with differential methylation of cg27535305 and cg13461509, located in the promoter regions of both genes. To conclude, using an approach that combines genetic and epigenetic data, we highlighted the CTNNBL1, SCP2 and ECHDC2 genes as potential contributors to drug dependence susceptibility.

Effective connectivity predicts cognitive empathy in cocaine addiction: a spectral dynamic causal modeling study.

Social cognition plays a crucial role in the development and treatment of cocaine dependence. However, studies investigating social cognition, such as empathy and its underlying neural basis, are lacking. To explore the neural interactions among reward and memory circuits, we applied effective connectivity analysis on resting-state fMRI data collected from cocaine-dependent subjects. The relationship between effective connectivity within these two important circuits and empathy ability - evaluated with the Interpersonal Reactivity Index (IRI) - was assessed by machine learning algorithm using multivariate regression analysis. In accordance with the neurocircuitry disruptions of cocaine addiction, the results showed that cocaine-dependent subjects relative to healthy controls had altered resting state effective connectivity between parts of the memory and reward systems. Furthermore, effective connectivity between the memory and reward system could predict the fantasy empathy (FE) subscale scores in cocaine dependence. Overall, our findings provide further evidence for the neural substrates of social cognition in cocaine-dependent patients. These new insights could be useful for the development of new treatment programs for this substance dependency disorder.

The Efficacy of Lidocaine in Disrupting Cocaine Cue-Induced Memory Reconsolidation

RationalCue-induced craving memories, linked to drug-seeking behaviors, require key molecular processes for memory reconsolidation. Lidocaine, a sodium channel blocker, inhibits NMDA receptor activation and suppresses nitric oxide and ERK production. These processes are required for memory re-consolidation; inhibiting them may reduce cue-related craving memories in cocaine dependent subjects. ObjectivesTo assess the efficacy of lidocaine in decreasing cue-induced cocaine craving and cocaine use. MethodsTreatment-seeking cocaine-dependent participants (n = 33, 25 men) were recruited. Personalized craving and relaxation scripts were developed. Participants were then randomly assigned in a double-blind design to either receive intravenous lidocaine immediately following a cocaine craving script (lidocaine/craving), saline following a craving script (saline/craving), or lidocaine following a relaxation script (lidocaine/relax). One week following the infusion, cue-induced craving was assessed in the same paradigm without an infusion. Cocaine use and craving were assessed for 4 weeks following infusion. ResultsThe administration of lidocaine during craving induction (lidocaine/craving) did not decrease cue-induced craving during craving reactivation one week later or craving and cocaine use over the 4-week follow-up period compared to the saline/craving group. There were no significant differences in craving and cocaine use between the lidocaine/relax and saline/craving groups. ConclusionLidocaine administered following craving induction did not decrease subsequent cue-induced craving or cocaine use. Blocking the reconsolidation of craving-related memories with pharmacological agents remains an important area of investigation.

Imaging Cortical Dopamine Transmission in Cocaine Dependence: A [11C]FLB 457–Amphetamine Positron Emission Tomography Study

BackgroundPositron emission tomography studies have demonstrated less dopamine D2/3 receptor availability and blunted psychostimulant-induced dopamine release in cocaine-dependent subjects (CDSs). No studies in CDSs have reported the in vivo status of D2/3 and dopamine release in the cortex. Basic and functional imaging studies suggest a role for prefrontal cortical dopaminergic abnormalities in impaired executive function and relapse in cocaine dependence. We used [11C]FLB 457 positron emission tomography and amphetamine to measure cortical D2/3 receptors and dopamine release in CDSs. Methods[11C]FLB 457 and positron emission tomography were used to measure D2/3 receptor binding potential in cortical regions of interest in recently abstinent CDSs (n = 24) and healthy control subjects (n = 36) both before and after 0.5 mg kg−1 of oral d-amphetamine. Binding potential relative to nondisplaceable uptake (BPND) and binding potential relative to total plasma concentration (BPP) were derived using an arterial input function-based kinetic analysis. Cortical dopamine release in regions of interest was measured as the change in BPND and BPP after amphetamine. ResultsBaseline D2/3 receptor availability (BPP and BPND) and amphetamine-induced dopamine release (ΔBPND and ΔBPP) were significantly lower in the cortical regions in CDSs compared with healthy control subjects. Fewer D2/3 receptors and less dopamine release in CDSs were not associated with performance on working memory and attention tasks. ConclusionsThe results of this study suggest that deficits in dopamine D2/3 transmission involve the cortex in cocaine dependence. Further studies to understand the clinical relevance of these findings are warranted.

Significant, replicable, and functional associations between KTN1 variants and alcohol and drug codependence.

The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between KTN1 SNPs and SUD across multiple samples. We examined the associations between SUD and KTN1 SNPs in four independent population-based or family-based samples (n = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on KTN1 mRNA expression, and the relationship between KTN1 mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 × 10-4 ≤ p ≤ 0.049), including one SNP (rs12895072) across three samples (8.8 × 10-3 ≤ p ≤ 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European-Australians (4.8 × 10-4 ≤ p ≤ 0.058). All of the SUD-risk alleles of these 27 SNPs increased (β > 0) the putamen GMVs and represented major alleles (f > 0.5) in Europeans. Twenty-two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the KTN1 mRNA expression, and the KTN1 mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the KTN1 variants, KTN1 mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk KTN1 alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD.

Neural correlates of oxytocin and cue reactivity in cocaine-dependent men and women with and without childhood trauma.

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.

Association of the PLCB1 gene with drug dependence

Genetic factors involved in the susceptibility to drug addiction still remain largely unknown. MiRNAs seem to play key roles in the drug-induced plasticity of the brain that likely drives the emergence of addiction. In this work we explored the role of miRNAs in drug addiction. With this aim, we selected 62 SNPs located in the 3’UTR of target genes that are predicted to alter the binding of miRNA molecules and performed a case-control association study in a Spanish sample of 735 cases (mainly cocaine-dependent subjects with multiple drug dependencies) and 739 controls. We found an association between rs1047383 in the PLCB1 gene and drug dependence that was replicated in an independent sample (663 cases and 667 controls). Then we selected 9 miRNAs predicted to bind the rs1047383 region, but none of them showed any effect on PLCB1 expression. We also assessed two miRNAs binding a region that contains a SNP in linkage disequilibrium with rs1047383, but although one of them, hsa-miR-582, was found to downregulate PLCB1, no differences were observed between alleles. Finally, we explored the possibility that PLCB1 expression is altered by cocaine and we observed a significant upregulation of the gene in the nucleus accumbens of cocaine abusers and in human dopaminergic-like neurons after cocaine treatment. Our results, together with previous studies, suggest that PLCB1 participates in the susceptibility to drug dependence.

Cannabis and cue-induced craving in cocaine-dependent individuals: A pilot study

BackgroundCannabis consumption is common among cocaine users; however, little is known about its effect on cocaine craving. The objective of this study was to assess whether cannabis co-use is associated with lower cue-induced cocaine craving in non-treatment-seeking cocaine-dependent individuals. MethodsData from twenty-eight cocaine-dependent men were analyzed in this pilot study. Cocaine-dependent subjects (n=12) were compared with cocaine-dependent subjects who also abused or were dependent on cannabis (n=16). After at least 72h of cocaine abstinence, verified using the Timeline Followback and a drug screening test, subjects participated in a functional magnetic resonance imaging session during which neutral and drug cue video sequences were presented. Each sequence comprised four video blocks alternating with resting blocks. We report here subjective craving measures that were collected using the Visual Analog Scale, administered before and after each video block as per standard craving measurement paradigms. ResultsCocaine craving was successfully induced, with no significant difference in cue-induced craving between the two groups. However, post-hoc analyses revealed a significant increase in pre-video cocaine craving scores over time among individuals with cannabis use disorders. ConclusionWe could not highlight significant differences in cocaine craving induction between groups, but we observed a possible deficit in craving decay in the cocaine and cannabis group. In light of this finding, methodology of craving assessment in non-treatment-seeking users, particularly when different substances are combined, should possibly include outcomes linked to craving decay. Studies examining the association between cocaine craving decay and other outcome measures, such as relapse, are also warranted.

Acute tryptophan depletion in cocaine dependent subjects with comorbid depression

Acute tryptophan depletion in cocaine dependent subjects with comorbid depression

Topiramate increases the rewarding properties of cocaine in young-adult mice limiting its clinical usefulness.

Topiramate is an anticonvulsant drug which has been evaluated as a therapeutic option for the treatment of cocaine addiction during the last decade. The purpose of this study was to evaluate the effects of topiramate on the reinforcing actions of cocaine. To this aim, the topiramate-mediated regulation of acquisition and extinction phases of the cocaine conditioned place preference (CPP) was assessed in young-adult mice using three experimental designs. Topiramate (50mg/kg, p.o.) was given as follows: (1) during cocaine (1 and 25mg/kg, i.p.) conditioning sessions (4days) and cocaine (25mg/kg) post-conditioning session; (2) 2weeks before and during cocaine conditioning (25mg/kg); and (3) during extinction of CPP induced by cocaine (25mg/kg). In the first experimental design, changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene expressions were measured in the ventral tegmental area (VTA). Topiramate significantly increased cocaine-induced CPP and delayed or failed to produce extinction after the first cocaine reinstatement extinction in the first and second experiments. Furthermore, treatment with topiramate after place conditioning blocked the extinction of cocaine-induced CPP. TH and DAT gene expression in the VTA was significantly lower both with topiramate alone and in combination with cocaine compared with animals receiving only cocaine. These findings suggest that topiramate increases the rewarding properties of cocaine, at least in part, by regulating dopaminergic signaling in the mesolimbic circuit. Consequently, the results of this study do not support the use of topiramate for the treatment of problems related to cocaine dependence. • Topiramate increases the rewarding properties of cocaine in CPP • Topiramate alters dopaminergic signaling in the mesolimbic circuit • Topiramate delays the extinction of cocaine-induced CPP • TH and DAT gene expression in the VTA decreases with topiramate and/or with cocaine • Results show that it should limit the use of topiramate in cocaine-dependent subjects.

The importance of viewing sleep as a 'practice'.

There is now a growing body of work which highlights how sleep can affect addiction/dependence and vice versa. Irwin and colleagues add further, valuable, detail to this. Individuals conceptualize sleep very differently depending on their experiences and circumstances, and this should be taken into account in future research and treatment discussions. It is well documented that sleep problems can contribute to the development of dependence, are made worse by chronic use, can persist into abstinence and are implicated in relapse 1. The current paper by Irwin and colleagues 2 adds further detail to this, most notably with the suggestion that cocaine and alcohol dependence accelerate age-related loss of stage 3 sleep and that this is much more pronounced in cocaine-dependent subjects. Reductions in sleep continuity—which usually accompany age-related reductions in slow wave activity 3are not observed. As the authors note, further studies are needed to determine clinical and prognostic significance. In moving forward, however, we need to acknowledge the multi-disciplinary nature of sleep and its study. Recent sociological research has, for example, argued that sleep is best considered as a ‘body technique’ or ‘practice’. By this, sociologists mean that sleep is more than a simple biological necessity and that how we sleep, when we sleep, where we sleep and the meanings and values we accord sleep are all historically and patterned socio-culturally 4. Viewing sleep in this way, rather than as an individualized health ‘behaviour’, frames it as something that emerges out of actions and interactions in specific contexts 5. For example, in one of the few studies to apply this framework to sleep and recovery, Nettleton and colleagues argue that the drive to avoid significant others and fraught social relationships can lead heroin-dependent individuals to be active during the night and sleep during the day. This non-adherence to diurnal sleep patterns can continue for decades, and the processes of reversing it can become a symbolic and pragmatic indicator of recovery 6. Viewing sleep in this wider frame feeds directly back to some of the important issues raised by Irwin et al.’s paper: first, sleep and dependence are complex and located within changing contexts. Irwin et al. begin to capture this. However, longitudinal data, talking to people about their past lives and sleep practices would assist further in understanding these and other findings 6. Secondly, Irwin et al. add to earlier research which finds that cocaine-dependent individuals often report their sleep subjectively as fine, even when accompanied by deterioration in objectively reported sleep parameters—a phenomenon described previously as ‘occult insomnia’ 7. They also raise interesting questions about sleep propensity within this population. Studies of older adults have suggested that age-related changes in slow wave sleep/slow wave activity may reflect a reduction in the amount of sleep needed by older adults to function well 3. Sociologists also remind us that individual meanings and values of sleep can vary. Venn & Arber 8, for example, highlight the different ways people talk about daytime sleep and how each of these carries specific meanings and connotations. In their research, daytime sleep was rarely spoken of as a ‘nap’, because this signified unwelcome ageing. Rather, where it did occur, daytime sleep was acknowledged as a ‘doze’ and not really sleeping. Studies have yet to explore fully the meanings and values of sleep within cocaine and alcohol dependence, but it may be that we need to think differently about subjective measures of sleep quality and ask ‘what is sleep’ a little more. Finally, cognitive–behavioural therapy for insomnia (CBT-I) may improve homeostatic sleep regulation and therefore has the potential to rebuild deficiencies in slow wave sleep 9. However, CBT-I has had limited success when used in alcohol-related disorders, in large part, it is suggested, because there remains a need to understand experiences throughout recovery 10. Treatment options bring more opportunities for multi-disciplinary discussion. If we accept that sleep is a complex practice which emerges out of actions and interactions within specific contexts, we need to draw upon a range of disciplines to best capture detailed patient experiences of both sleep and treatment options. None.

Psychiatric comorbidity in a sample of cocaine-dependent outpatients seen in the Community of Madrid drug addiction care network.

The objective of this study was to estimate the current prevalence of psychiatric disorders in cocaine-dependent patients who attend different treatment centres in the Community of Madrid. A prospective multicentre study was used, and a total of 197 cocaine-dependent subjects were assessed. The assessment instrument used for diagnosis was the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). The main findings of this study were a high prevalence of psychiatric comorbidity in cocaine-dependent patients seeking treatment (64.0%). The most common Non Substance Use Disorders found were attention-deficit/hyperactivity Disorders (34.5%) and depressive disorders (13.7%). The most common Substance Use Disorder was alcohol dependence (28.4%). Cocaine-dependent patients who had a depressive disorder and were alcohol dependent presented a more severe clinical profile and a higher degree of psychopathology, measured using different assessment tools, than the patients who were only cocaine dependent. These data suggest that the presence of psychiatric comorbidity could constitute a risk factor associated with the severity of cocaine dependence. The clinical heterogeneity found also indicates the need to search for individualised treatments that more specifically fit the needs of this population.

Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women

ObjectivesFluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine. Furthermore, our laboratory has demonstrated that following drug-cue exposure, cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and drug craving compared to cocaine dependent women with low levels of progesterone. In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone (ALLO) on stress arousal, inhibitory control and drug craving in cocaine dependent subjects. MethodsPlasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone (15M/8F) (400mg/day) or placebo (14M/9F) administered in a double blind, randomized manner. As a control, levels of the testosterone derived neurosteroid androstanediol (ADIOL) were also measured. All subjects participated in laboratory sessions on days 5–7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation, cocaine use or of a neutral setting and dependent variables including subjective craving, mood, Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed. Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups. ResultsProgesterone relative to placebo significantly increased ALLO levels with no sex differences. There were no effects of micronized progesterone on the testosterone derived ADIOL. Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline, and a higher cortisol response to stress; higher positive mood scores at baseline and improved Stroop performance in the drug-cue and stress conditions, and reduced cocaine craving across all imagery conditions. ConclusionsAs expected, cocaine dependent individuals administered progesterone showed significantly higher ALLO plasma levels. High levels of ALLO appeared to normalize basal and stress response levels of cortisol, decrease cocaine craving and also contribute to improvements in positive emotion and Stroop performance in response to stress and drug-cue exposures. These findings suggest that the neuroactive steroid ALLO plays a significant role in mediating the positive effects of progesterone on stress arousal, cognitive performance and drug craving in cocaine dependence.

“Smoking pot helps me focus”: A qualitative analysis of Internet forum discussions of ADHD and cannabis use

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e153 Online feasibility study about HIV-negative male couples substance use with weekly ecological momentary diary assessments Jason W. Mitchell 1, Francesca Davis1, Yue Pan2, Daniel J. Feaster1 1 Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, United States 2 University of Miami Miller School of Medicine, Miami, FL, United States Aims: To date, little is known about male couples’ use of substances despite the role that substance use plays in HIV seroconversion among gay men. The aims of the present study were twofold: (1) to assess whether panel dyadic data could be collected from HIV-negative male couples about their substance use using online weekly ecological momentary diary assessments; (2) to examine couples’ rates of substance use and contexts of their usage. Methods: A longitudinal study design using ecological momentary weekly electronic diaries was used to examine male couples substance use with/out sex, and the contexts of their usage over a 6-week period. Targeted facebook ads were used to recruit the sample along with a partner referral system to invite eligible participants’ main partners. 531 men took the screener; of these, 97 were eligible, consented and enrolled in the study. Results:Although97partneredmenenrolled, only 13male couples with both partners and 15 male couples with one partner participated in the study. Over the 6-week period, men’s engagement inUASwith theirmain partner, alcohol consumption, and use of erectile dysfunction medication, prescription pain medication (PPM), and/or illicit drug(s) varied. Men frequently usedmarijuana and/or alcohol in a variety of contexts including sex. Among the 13 male couples, both partner’s use of illicit drugs includingmarijuana (ICC 0.97, P 5 posts for analysis. Results: Qualitative analysis of individual posts indicated that Internet discussionparticipants emphasized the therapeutic effects of cannabis for ADHD – fewer endorsed either a null or harmful impact. Exploratory analysis also indicated that participants perceived fewer concerns about cannabis due to it being “natural,” that cannabis is perceived to improve impairment in ADHD (e.g., driving), distrust of the medical community regarding stimulant medication efficacy, and a preference for particular cannabis strains. Conclusions: Cannabis use in the US is changing and there is a need for further research of how cannabis impacts at-risk groups, such as those with ADHD. This qualitative study provides new insight into currentlyheldperceptions about cannabisuse inADHD. We propose a number of novel hypotheses guided by qualitative analysis ofweb-forumcontent,which canguide future quantitative e154 Abstracts / Drug and Alcohol Dependence 156 (2015) e102–e182 studies. This study also illustrates the potential use of web-based data to study substance use. Financial support: NIDA (K23 DA032577). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.418 Sex differences in intrinsic connectivity during FMRI stroop in cocaine-dependent and healthy comparison subjects Marci R. Mitchell 1, Elise E. DeVito1, I. Balodis1, Cheryl Lacadie2, Dustin Scheinost3, R. Todd Constable2, Robert Malison1, Kathleen M. Carroll 1, Marc N. Potenza1 1 Psychiatry, Yale University School of Medicine, New Haven, CT, United States 2 Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States 3 Biomedical Engineering, Yale University School of Medicine, New Haven, CT, United States Aims: Previouslywe found cocaine-dependent (CD) versus control subjects (HC) showed greater mean-adjusted connectivity in the ventral striatum, putamen, inferior frontal gyrus, anterior insula, thalamusandsubstantianigra.However, theextent towhich womenandmen showeddifferences in functional connectivitywas not previously examined. This study investigated sex differences in intrinsic connectivity distribution (ICD) in CD subjects during fMRI Stroop performance. Methods: 38 current CD (19 female) and 38 matched HC subjects (19 female) completed an fMRI Stroop task. Mean-adjusted ICD analyses were conducted to identify sex differences. Results: Both increases and decreases in connectivity were observed in all four comparisons (Females CD–HC; Males CD–HC; CD Males–Females; HC Males–Females), and an interaction between gender and diagnostic group implicated connectivity differences in the orbitofrontal cortex (OFC), ventral striatum, precuneus/cuneus, cingulate gyrus, and occipital lobe. Out-of-scanner behavioral Stroop data did not reveal differences between males and females between diagnostic groups, but did show sex differences within the CD group but not the HC group. Conclusions: Differences in intrinsic connectivity involved the OFC, cingulate, and striatum, areas implicated in cocaine dependence and cognitive processes including decision-making and inhibitory control. Differences in regions associated with language and visual processing were also observed. The extent to which these patterns of connectivity relate to clinically relevant measures of cocainedependencewarrants additional investigation. Financial Support: ORWH, OD, NIDA (K12-DA031050, R01DA020908, R01-DA035058, P50-DA09241, R01-DA019039, P20DA027844). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.419 Counselors’ views of providing patient-centered methadone treatment in a clinical trial Shannon G. Mitchell 1, Laura Monico1, Elizabeth Lertch1, Jan Gryczynski1, Sharon M. Kelly1, K.E. O’Grady2, Jerome H. Jaffe1, Robert P. Schwartz1 1 Friends Research Institute, Baltimore, MD, United States 2 University of Maryland, College Park, MD, United

Sex differences in intrinsic connectivity during FMRI stroop in cocaine-dependent and healthy comparison subjects

Sex differences in intrinsic connectivity during FMRI stroop in cocaine-dependent and healthy comparison subjects

Differential brain response to successful and failed response inhibition: Cocaine-dependent vs. healthy subjects

to GDC (n=58). Characteristics of women with a history of sexual abuse were examined in these post-hoc analyses. Methods: Participants ≥18 years with SUDs were included if they used substances in past 60 days. Sexual abuse (SA) history was assessed using the Life ExperiencesQuestionnaire; functioning with theGlobalAssessmentof Functioning (GAF) scale; and theCIDI was used to determine psychiatric diagnoses. Results: Of the 100 women in the trial, 39% reported a history of SA. Compared to women without a history of SA, those with a SA history had lower GAF scores (t=2.7, df = 98, p< .01) and higher rates ofmajor depressive disorder (85% vs. 64%; 2(1) =5.05, p< .05), PTSD (39% vs. 13%; 2(1) =8.63, p< .01), and panic disorder (26% vs. 8%; 2(1) =5.68, p< .05).We dividedwomen into 3 groups: (1) no history of SA, (2) SA either before OR after age 16, and (3) SA before AND after age 16. Women with abuse before and after had the lowest GAF scores (M=56, SD=4.7), followed by those with one type of abuse (M=59, SD=5.7); women with no history had the highest GAF scores (M=61, SD=5.3). Women assigned to the GDC group who had a history of SA rated the helpfulness of having men and women in the group as significantly lower than those without a history of SA (t=−2.4, df = 40, p< .05);women in theWRG rated the helpfulness of the all-women group composition as high regardless of SA history. Conclusions: Women with SA history had lower functioning and greater psychiatric comorbidity. Single-gender SUD group composition was endorsed as helpful by those with and without SA history but may be especially importantfor those who have experienced sexual abuse. Financial Support: NIDA R01 DA015434 and K24 DA019855.

Inhibitory control: A brain connectivity study comparing cocaine-dependent subjects and controls

Inhibitory control: A brain connectivity study comparing cocaine-dependent subjects and controls