Cocaine-dependent Participants Research Articles

Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4mg BUP (BUP4), 16mg BUP (BUP16), or placebo (PLB) for 8weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Methylation of the serotonin transporter gene moderates the depressive subjective effect of cocaine

Genetic variation in the serotonin transporter (SLC6A4) has been shown to moderate the acute subjective effects of cocaine. Methylation of the SLC6A4 gene is associated with decreased transcription of the serotonin transporter, leading to increased serotonin in the synapse. In this study, methylation of the SLC6A4 gene was investigated in the moderation of the subjective effects of cocaine. Non-treatment-seeking cocaine-dependent individuals (N = 53) were intravenously administered cocaine (40 mg) and saline in a randomized order. The subjective effects of cocaine were self-reported using a visual analog scale starting prior to the administration of cocaine (−15 min) or saline and up to 20 min after infusion. Participants were evaluated for methylation of the SLC6A4 promoter region and 5-HTTLPR genotype. A series of ANCOVAs for SLC6A4 methylation (high/low) were run for each of ten subjective and three cardiovascular effects controlling for age, sex [utilizing the sex-determining region Y protein (SRY)], and population structure (determined from ancestry informative markers and STRUCTURE software). Participants with SLC6A4 hypermethylation reported greater subjective response to cocaine for ‘depressed’ relative to participants with SLC6A4 hypomethylation (experiment-wise p = 0.002). These findings indicate that SLC6A4 methylation moderates the ‘depressed’ subjective effect of cocaine in non-treatment-seeking cocaine-dependent participants.

Assessing combinatorial effects of HIV infection and former cocaine dependence on cognitive control processes: A high-density electrical mapping study of response inhibition

Stimulant drug use in HIV + patients is associated with poor personal and public health outcomes, including high-risk sexual behavior and faster progression from HIV to AIDS. Inhibitory control--the ability to withhold a thought, feeling, or action--is a central construct involved in the minimization of risk-taking behaviors. Recent neuroimaging and behavioral evidence indicate normalization of inhibitory control processes in former cocaine users as a function of the duration of drug abstinence, but it is unknown whether this recovery trajectory persists in former users with comorbid HIV. Here, we investigate the neural correlates of inhibitory control in 103 human subjects using high-density EEG recording as participants performed a Go/NoGo response inhibition task. Four groups of participants were recruited, varying on HIV and cocaine-dependence status. Electrophysiological responses to successful inhibitions and behavioral task performance were compared among groups. Results indicate persistent behavioral and neurophysiological impairment in HIV+ patients’ response inhibition despite current abstinence from cocaine. Analysis of task performance showed that HIV+ abstinent cocaine-dependent participants demonstrate the lowest performance of all groups across all metrics of task accuracy. Planned comparisons of electrophysiological components revealed a main effect of scalp site and an interaction between HIV-status and scalp site on N2 amplitudes during successful inhibitions. Analysis of the P3 time region showed a main effect of scalp site and an interaction between HIV-status and cocaine dependence. These results suggest synergistic alterations in the neurophysiology of response inhibition and indicate that abstinence-related recovery of inhibitory control may be attenuated in patients with HIV.

Cue-elicited functional connectivity of the periaqueductal gray and tonic cocaine craving

BackgroundWithdrawal from chronic cocaine use leads to anxiety and dysphoria that may perpetuate habitual drug use. The pain circuit is widely implicated in the processing and manifestations of negative emotions. Numerous studies have focused on characterizing reward circuit dysfunction but relatively little is known about the pain circuit response during cocaine withdrawal. MethodsHere we examined the activity and connectivity of the periaqueductal gray (PAG), a hub of the pain circuit, during cocaine cue exposure in 52 recently abstinent cocaine dependent participants (CD, 42 men). Imaging data were processed with published routines, and the results were evaluated at a corrected threshold. ResultsCD showed higher activation of the PAG and connectivity of the PAG with the ventromedial prefrontal cortex (vmPFC) during cocaine as compared to neutral cue exposure. PAG-vmPFC connectivity was positively and negatively correlated with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire, in male and female CD, respectively, and the sex difference was confirmed by a slope test. Granger causality analyses showed that the PAG Granger caused vmPFC time series in men and the reverse was true in women, substantiating sex differences in the directional interactions of the PAG and vmPFC. ConclusionThe findings provide the first evidence in humans implicating the PAG circuit in cocaine withdrawal and cocaine craving and advance our understanding of the role of the pain circuit and negative reinforcement in sustaining habitual drug use in cocaine addiction.

Methylation Patterns of the HTR2A Associate With Relapse-Related Behaviors in Cocaine-Dependent Participants

Relapse during abstinence in cocaine use disorder (CUD) is often hastened by high impulsivity (predisposition toward rapid unplanned reactions to stimuli without regard to negative consequences) and high cue reactivity (e.g., attentional bias towards drug reward stimuli). A deeper understanding of the degree to which individual biological differences predict or promote problematic behaviors may afford opportunities for clinical refinement and optimization of CUD diagnostics and/or therapies. Preclinical evidence implicates serotonin (5-HT) neurotransmission through the 5-HT2A receptor (5-HT2AR) as a driver of individual differences in these relapse-related behaviors. Regulation of 5-HT2AR function occurs through many mechanisms, including DNA methylation of the HTR2A gene, an epigenetic modification linked with the memory of gene-environment interactions. In the present study, we tested the hypothesis that methylation of the HTR2A may associate with relapse-related behavioral vulnerability in cocaine-dependent participants versus healthy controls. Impulsivity was assessed by self-report (Barratt Impulsiveness Scale; BIS-11) and the delay discounting task, while levels of cue reactivity were determined by performance in the cocaine-word Stroop task. Genomic DNA was extracted from lymphocytes and the bisulfite-treated DNA was subjected to pyrosequencing to determine degree of methylation at four cytosine residues of the HTR2A promoter (-1439, -1420, -1224, -253). We found that the percent methylation at site -1224 after correction for age trended towards a positive correlation with total BIS-11 scores in cocaine users, but not healthy controls. Percent methylation at site -1420 negatively correlated with rates of delay discounting in healthy controls, but not cocaine users. Lastly, the percent methylation at site -253 positively correlated with attentional bias toward cocaine-associated cues. DNA methylation at these cytosine residues of the HTR2A promoter may be differentially associated with impulsivity or cocaine-associated environmental cues. Taken together, these data suggest that methylation of the HTR2A may contribute to individual differences in relapse-related behaviors in CUD.

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.

Unpacking common and distinct neuroanatomical alterations in cocaine dependent versus pathological gambling

Pathological gambling and cocaine dependence are highly pervasive disorders. Functional neuroimaging evidence implicates aberrant activity of prefrontal striatal pathways in both disorders. It is unclear if the neuroanatomy of these areas is also affected. Participants with pathological gambling (n = 18), cocaine dependence (n = 19) and controls (n = 21) underwent high-resolution structural MRI scan and cognitive assessments. In line with emerging functional neuroimaging findings, we hypothesised (i) lower volumes of corticostriatal areas ascribed to decision-making/inhibitory control, craving and reward processing (i.e., orbitofrontal cortex, inferior frontal gyrus, amygdala, striatum, insula) in both pathological gamblers and cocaine dependent participants versus controls; (ii) selected dopaminergic/glutamatergic pathways directly taxed by cocaine (i.e., superior, dorsolateral and anterior cingulate cortices) would be altered in cocaine dependent versus control participants only. Analyses were conducted with a bonferroni correction. Our results showed that both pathological gambling and cocaine dependent participants, compared to controls, had larger volumes of the right inferior frontal gyrus (ps <.01, ds = 0.66 and 0.62). Cocaine dependent participants had lower nucleus accumbens and medial orbitofrontal cortex volumes than pathological gamblers (ps <.05, ds = 0.51 and 0.72), with the latter being predicted by higher negative urgency scores. Inferior frontal gyrus volume may reflect common alterations of cocaine and gambling addictions, whereas cocaine dependence may be uniquely associated with reduced volume in dorsolateral and middle frontal regions. Cocaine's supra-physiological effects on mesolimbic neurons may explain reduced accumbens-orbitofrontal structure compared to gambling.

History of withdrawal modulates drug- and food-cue reactivity in cocaine dependent participants

While the centrality of withdrawal in the diagnosis of addiction has been decreasing with each successive edition of the Diagnostic and Statistical Manual of Mental Disorders, psychometric and neurobiological evidence provides withdrawal a central role in the development and maintenance of addiction. The current study offers insight into these conflicting positions by using secondary analyses to assess how a history of DSM-assessed withdrawal influences the magnitude of bias in neural reactivity to drug- and/or food-related reward cues. To this end, we separated an existing sample of cocaine-dependent participants (Denomme et al., 2018) into those with (WD) and without (N-WD) a history of withdrawal, and compared food- and drug-cue reactivity between these groups, and to a non-dependent control group (ND). Analyses indicated that biases in neural reactivity towards drug- versus food-related cues only occurred among the WD participants (within: left dorsomedial prefrontal cortex, left anterior cingulate cortex, left orbitofrontal cortex, left caudate nucleus, and right ventrolateral prefrontal cortex). Thus, withdrawal status may be an important factor to consider when interpreting dependence-related biases in neural reactivity following reward-related cues. Interestingly, while N-WD participants did not show these broad biases in neural reactivity, the magnitude of their bias correlated positively with years of lifetime substance use history, particularly when psychopathic traits were low. It may be that for individuals who’s addiction has not yet reached a compulsive state (see Wise and Koob, 2014), the magnitude of their drug > food bias could serve as a valuable biomarker of addiction severity.

Hypothalamic Responses to Cocaine and Food Cues in Individuals with Cocaine Dependence.

BackgroundIndividuals with cocaine addiction are characterized by under-responsiveness to natural reinforcers. As part of the dopaminergic pathways, the hypothalamus supports motivated behaviors. Rodent studies suggested inter-related roles of the hypothalamus in regulating drug and food intake. However, few studies have investigated hypothalamic responses to drugs and food or related cues in humans.MethodsWe examined regional responses in 20 cocaine-dependent and 24 healthy control participants exposed to cocaine/food (cocaine dependent) and food (healthy control) vs neutral cues during functional magnetic resonance imaging. We examined the relationship between imaging findings and clinical variables and performed mediation analyses to examine the inter-relationships between cue-related activations, tonic cocaine craving, and recent cocaine use.ResultsAt a corrected threshold, cocaine-dependent participants demonstrated higher activation to cocaine than to food cues in the hypothalamus, inferior parietal cortex, and visual cortex. Cocaine-dependent participants as compared with healthy control participants also demonstrated higher hypothalamic activation to food cues. Further, the extent of these cue-induced hypothalamic activations was correlated with tonic craving, as assessed by the Cocaine Craving Questionnaire, and days of cocaine use in the prior month. In mediation analyses, hypothalamic activation to cocaine and food cues both completely mediated the relationship between the Cocaine Craving Questionnaire score and days of cocaine use in the past month.ConclusionsThe results were consistent with the proposition that the mechanisms of feeding and drug addiction are inter-linked in the hypothalamus and altered in cocaine addiction. The findings provide new evidence in support of hypothalamic dysfunction in cocaine addiction.

Classification of cocaine-dependent participants with dynamic functional connectivity from functional magnetic resonance imaging data.

Static functional connectivity (FC) analyses based on functional magnetic resonance imaging (fMRI) data have been extensively explored for studying various psychiatric conditions in the brain, including cocaine addiction. A recently emerging, more powerful technique, dynamic functional connectivity (DFC), studies how the FC dynamics change during the course of the fMRI experiments. The aim in this paper was to develop a computational approach, using a machine learning framework, to determine if DFC features were more successful than FC features in the classification of cocaine-dependent patients and healthy controls. fMRI data were obtained from of 25 healthy and 58 cocaine-dependent participants while performing a motor response inhibition task, stop signal task. Group independent component analysis was carried out on all participant data to compute spatially independent components (ICs). Eight ICs were selected manually as relevant brain networks, which were used to classify healthy versus cocaine-dependent participants. FC and DFC measures of the chosen IC pairs were used as features for the classification algorithm. Support Vector Machines were used for both feature selection/reduction and participant classification. Based on DFC with only seven IC pairs, participants were successfully classified with 95% accuracy (and with 90% accuracy with three IC pairs), whereas static FC yielded only 81% accuracy. Visual, sensorimotor, default mode, and executive control networks, amygdala, and insula played the most significant role in the DFC-based classification. These findings support the use of DFC-based classification of fMRI data as a potential biomarker for the identification of cocaine dependence.

Substance use outcomes in cocaine-dependent tobacco smokers: A mediation analysis exploring the role of sleep disturbance, craving, anxiety, and depression

BackgroundSleep disturbance may play a role in cocaine use outcomes and, hence, may be a potential therapeutic target for cocaine use disorder (CUD). Research in this area, which has largely relied on resource-intensive polysomnography, would be facilitated by identifying a self-report sleep measure predictive of CUD outcomes and by a better understanding of the mechanisms by which sleep may impact CUD outcomes. This study tested the predictive validity of the Pittsburgh Sleep Quality Index (PSQI), a self-report assessment of past-month sleep quality. To better understand potential mechanisms, mediation models relating sleep disturbance to CUD outcomes were evaluated. MethodsThis is a secondary analysis of data from cocaine-dependent (n = 290) participants in a multi-site trial evaluating smoking-cessation treatment for stimulant-dependent patients. The PSQI was collected at baseline; the outcomes of interest were cocaine and drug abstinence at end-of-treatment (weeks 9–10). Potential mediators, measured in weeks 1–8, were: cocaine craving (Brief Substance Craving Scale); and anxiety and depression symptoms (Hospital Anxiety and Depression Scale). Mediation techniques were used to evaluate mediation effects separately and jointly. ResultsThe majority of participants (58.3%) had baseline sleep disturbance. Sleep disturbance was not a significant predictor of end-of-treatment abstinence when regressed without consideration of mediators. Cocaine craving, anxiety, and depression were significant mediators, both separately and jointly, of an effect of baseline sleep disturbance on end-of-treatment abstinence. ConclusionThis exploratory analysis suggests that there may be an indirect relationship between self-reported sleep quality and substance use outcomes in cocaine-dependent patients, mediated by craving, anxiety, and depression.Trial registration:ClinicalTrials.gov: NCT01077024

Impulsivity and decision making in older and younger cocaine-dependent participants: A preliminary study

Substance misuse is increasing in the older population, which may have differing effects on behavior compared to younger substance participants. Differences in trait and state impulsivity were assessed in younger and older cocaine-dependent participants. Thirty-one younger cocaine-dependent participants (n = 31) and 21 older cocaine-dependent participants (n = 21) were assessed using the Barrett Impulsiveness Scale-11 and the Immediate Memory Task. Younger participants showed higher trait impulsivity than older participants (p =.027). However, older participants demonstrated higher state impulsivity than younger participants (p =.018). Higher state impulsivity in older cocaine participants suggests that cocaine use may have accelerating effects on the aging brain. This preliminary study adds the limited research on how cocaine use affects normal aging. Current treatments are based on younger adults, therefore the needs of older adults should be taken into consideration and studied more. (Am J Addict 2018;27:557-559).

Effect of continuing care for people with cocaine dependence on criminal justice sentences.

While continuing care for substance use treatment has been associated with reduced involvement in the criminal justice system, much of this research lacks random assignment to continuing care and so is limited by self-selection bias. This study sought to determine the impact of adding telephone-based continuing care to intensive outpatient programs on criminal justice outcomes for people with cocaine dependence. In three continuing care studies, spanning 1998-2008, participants were randomly assigned to an intensive outpatient program or an intensive outpatient program plus a telephone-based continuing care intervention. Cocaine-dependent participants from these three studies were included in the analyses, with outcomes derived from a dataset of jurisdiction-wide criminal sentences from a state sentencing agency. Multiple logistic regression was employed to examine the odds of a criminal conviction occurring in the 4years after enrollment in a continuing care study. The results showed that, controlling for a criminal sentence in the previous year, gender, age, and continuing care study, people with cocaine dependence randomized to an intensive outpatient program plus a telephone-based continuing care intervention had 54% lower odds (p = 0.05, odds ratio = 0.46, 95% CI: 0.20-1.02) of a criminal sentence in the 4years after enrollment in the continuing care study, compared with those randomized to an intensive outpatient program alone. We can conclude that adding telephone monitoring and counseling to intensive outpatient programs is associated with fewer criminal convictions over a 4-year follow-up period compared with intensive outpatient programs alone.

Genetic moderation of cocaine subjective effects by variation in the TPH1, TPH2, and SLC6A4 serotonin genes.

This study investigated variants of tryptophan hydroxylase (TPH)1, TPH2, and SLC6A4 in the moderation of the subjective effects of cocaine. Non-treatment-seeking cocaine-dependent individuals (N=66) were intravenously administered saline and cocaine (40 mg) in a randomized order. Participants self-reported subjective effects of cocaine using a visual analog scale starting before administration of saline or cocaine (-15 min) to up to 20 min after infusion. Self-report ratings on the visual analog scale ranged from 0 (no effect) to 100 (greatest effect). Participants were genotyped for the TPH1 rs1799913, TPH2 rs4290270, and SLC6A4 5-HTTLPR variants. Repeated-measures analysis of covariance was used to examine changes in subjective effect scores over time while controlling for population structure. Participants carrying the TPH1 rs1799913 A allele reported greater subjective response to cocaine for 'stimulated' and 'access' relative to the CC genotype group. Those carrying the TPH2 rs4290270 A allele reported higher 'good effect' and lower 'depressed' effect relative to the TT genotype group. Those carrying the SLC6A4 5-HTTLPR S' allele reported greater 'desire' and 'access' compared with the L'L' genotype group. These findings indicate that TPH1, TPH2, and SLC6A4 variants moderate the subjective effects of cocaine in non-treatment-seeking cocaine-dependent participants.

Changes in quality of life in cocaine-dependent participants provided treatment with buprenorphine + naloxone & extended release naltrexone

Changes in quality of life in cocaine-dependent participants provided treatment with buprenorphine + naloxone & extended release naltrexone

Carvedilol does not reduce cocaine use in methadone-maintained cocaine users

IntroductionThe goal of this study was too test the efficacy of carvedilol (CAR), an adrenergic blocker, for reducing cocaine use in individuals with cocaine use disorder (CUD). We conducted a 17-week, double-blind, randomized controlled trial with 3 treatment arms: 25mg CAR, 50mg CAR, and placebo. MethodsOne hundred and six treatment-seeking opioid and cocaine-dependent participants, who were also maintained on methadone during study participation, were randomized to placebo (n=34), 25mg/day CAR (n=37) or 50mg/day CAR (n=35). The main outcome measures were cocaine and opioid use as assessed by urine drug screening and self-reported drug use. ResultsNo significant group differences were found for treatment retention with 56% of the placebo, 76% of the 25mg and 66% of the 50mg CAR groups (p>0.05) completing treatment. The percentage (SD) of cocaine positive urines during the trial showed an overall treatment effect: 59.2 (38.9) for the placebo, 50.8 (33.8) for the 25mg and 75.1 (33.2) for the 50mg CAR group. In post hoc comparisons, neither the 25 nor 50mg CAR condition differed significantly from the placebo; however, the 25mg CAR group had a significantly lower proportion of cocaine-positive urines than the 50mg group. No significant group differences were found for the percentage of self-reported days of cocaine abstinence during the trial: 72.9 (25.3) for placebo, 72.9 (29) for CAR 25mg, and 59.3 (31.7) for CAR 50mg. Significant groups differences in the proportion of opioid positive urines submitted were not observed (p>0.05). Baseline cocaine withdrawal severity did not predict treatment response (p>0.05). ConclusionsThese findings did not support the efficacy of CAR for the treatment of cocaine use in cocaine and opioid dependent participants maintained on methadone. Further, CAR doses >25mg should not be used to avoid possible increases in cocaine and opioid use.

Successful classification of cocaine dependence using brain imaging: a generalizable machine learning approach.

BackgroundNeuroimaging studies have yielded significant advances in the understanding of neural processes relevant to the development and persistence of addiction. However, these advances have not explored extensively for diagnostic accuracy in human subjects. The aim of this study was to develop a statistical approach, using a machine learning framework, to correctly classify brain images of cocaine-dependent participants and healthy controls. In this study, a framework suitable for educing potential brain regions that differed between the two groups was developed and implemented. Single Photon Emission Computerized Tomography (SPECT) images obtained during rest or a saline infusion in three cohorts of 2–4 week abstinent cocaine-dependent participants (n = 93) and healthy controls (n = 69) were used to develop a classification model. An information theoretic-based feature selection algorithm was first conducted to reduce the number of voxels. A density-based clustering algorithm was then used to form spatially connected voxel clouds in three-dimensional space. A statistical classifier, Support Vectors Machine (SVM), was then used for participant classification. Statistically insignificant voxels of spatially connected brain regions were removed iteratively and classification accuracy was reported through the iterations.ResultsThe voxel-based analysis identified 1,500 spatially connected voxels in 30 distinct clusters after a grid search in SVM parameters. Participants were successfully classified with 0.88 and 0.89 F-measure accuracies in 10-fold cross validation (10xCV) and leave-one-out (LOO) approaches, respectively. Sensitivity and specificity were 0.90 and 0.89 for LOO; 0.83 and 0.83 for 10xCV. Many of the 30 selected clusters are highly relevant to the addictive process, including regions relevant to cognitive control, default mode network related self-referential thought, behavioral inhibition, and contextual memories. Relative hyperactivity and hypoactivity of regional cerebral blood flow in brain regions in cocaine-dependent participants are presented with corresponding level of significance.ConclusionsThe SVM-based approach successfully classified cocaine-dependent and healthy control participants using voxels selected with information theoretic-based and statistical methods from participants’ SPECT data. The regions found in this study align with brain regions reported in the literature. These findings support the future use of brain imaging and SVM-based classifier in the diagnosis of substance use disorders and furthering an understanding of their underlying pathology.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1218-z) contains supplementary material, which is available to authorized users.

Effect of Continuing Care for Cocaine Dependence on HIV Sex-Risk Behaviors.

Evaluate the effect of continuing care interventions for cocaine use with HIV risk-reduction components on HIV sex-risk. Explore whether cocaine use at treatment initiation interacts with the type of continuing care intervention to affect HIV sex-risk. Cocaine dependent participants (N=321) were randomized to: (1) Treatment as usual (TAU): intensive outpatient treatment, (2) TAU and telephone monitoring and counseling (TMC), and (3) TAU and TMC plus incentives for participation in telephone contacts (TMC+). Participants in TMC and TMC+ received a brief HIV intervention, with booster sessions as needed. Generalized estimating equations analysis compared TAU, TMC and TMC+ at 6, 12, 18, 24months post-baseline on the following outcomes: overall HIV sex-risk, number of sexual partners, condom usage, exchange of drugs for sex, exchange of sex for drugs, exchange of money for sex, exchange of sex for money, and crack house visits. Overall sex-risk decreased for all treatment conditions at follow-up, with no treatment main effects. For people with no cocaine use at baseline, TAU experienced greater sex-risk reductions than TMC (p<.01) and TMC+ (p<.001). The three treatment conditions are effective in reducing HIV sex-risk. TMC with HIV risk-reduction components is unnecessary for cocaine-dependent clients who stop using cocaine early in treatment.

Derived relations moderate the association between changes in the strength of commitment language and cocaine treatment response.

The psycholinguistic analysis of client-counselor interactions indicates that how individuals talk about their substance use is associated with treatment outcome. However, the processes by which client speech influences out-of-session behaviors have not been clearly delineated. This study investigated the relationships between deriving relations-a key behavioral process by which language and cognition may come to influence behavior, shifts in the strength of client talk in favor of change, and treatment outcome among 75 cocaine-dependent participants (23% Female). Participants were trained to relate cocaine words, nonsense syllables, and negative-consequence words and were then assessed for a derived relation of equivalence before starting treatment. The DARN-C coding system was used to quantify the strength of participant speech during an early cognitive behavior therapy counseling session. Cocaine use during treatment was the outcome of interest. The analyses (a) characterized the process of deriving relations among individuals seeking help for their misuse of cocaine, (b) tested the relationships between shifts in the strength of participants' speech in favor of change and treatment outcome, and (c) tested if deriving equivalence relations moderated the relationship between shifts in the strength of in-session speech and treatment response. Results indicated that a minority of participants derived equivalence relations, however increases in the strength of commitment language predicted less cocaine use during treatment only among those who did. The findings suggest deriving relations may be an important process by which changes in the strength of commitment language comes to influence substance use.

Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis.

Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence.