Cocaine-dependent Individuals Research Articles

Yohimbine administration and cue-reactivity in cocaine-dependent individuals.

Preclinical studies suggest that stress potentiates cue-induced cocaine seeking and that this effect is more pronounced in females. These findings have not been characterized in clinical populations. The objectives of this study were to examine the impact a pharmacological stressor, alpha-2 adrenergic receptor antagonist yohimbine, on the subjective, endocrine, and physiologic responses to drug-paired cues cocaine-dependent men and women. In a double-blind placebo-controlled cross-over study, cocaine-dependent men (n = 32), cocaine-dependent women (n = 30), control men (n = 32), and control women (n = 25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Yohimbine increased ratings of anxiety both before (p < 0.001) and after (p = 0.035) cues, and the post-cue increase in anxiety was more pronounced in women (p = 0.001). Yohimbine also significantly increased craving, compared with placebo (p < 0.05), following the cue presentation, and this effect was greater in women than men (gender by treatment interaction; p = 0.006). Yohimbine also increased salivary cortisol (p < 0.001) and dehydroepiandrosterone (p = 0.003) levels, regardless of diagnostic group. Women had a significantly greater heart rate response following yohimbine as compared with men (p < 0.001). Stress may increase the salience of cocaine cues for cocaine-dependent women as compared with men. This suggests gender differences in vulnerability to craving and relapse under stressful conditions.

Nipping Cue Reactivity in the Bud: Baclofen Prevents Limbic Activation Elicited by Subliminal Drug Cues

Relapse is a widely recognized and difficult to treat feature of the addictions. Substantial evidence implicates cue-triggered activation of the mesolimbic dopamine system as an important contributing factor. Even drug cues presented outside of conscious awareness (i.e., subliminally) produce robust activation within this circuitry, indicating the sensitivity and vulnerability of the brain to potentially problematic reward signals. Because pharmacological agents that prevent these early cue-induced responses could play an important role in relapse prevention, we examined whether baclofen-a GABAB receptor agonist that reduces mesolimbic dopamine release and conditioned drug responses in laboratory animals-could inhibit mesolimbic activation elicited by subliminal cocaine cues in cocaine-dependent individuals. Twenty cocaine-dependent participants were randomized to receive baclofen (60 mg/d; 20 mg t.i.d.) or placebo. Event-related BOLD fMRI and a backward-masking paradigm were used to examine the effects of baclofen on subliminal cocaine (vs neutral) cues. Sexual and aversive cues were included to examine specificity. We observed that baclofen-treated participants displayed significantly less activation in response to subliminal cocaine (vs neutral) cues, but not sexual or aversive (vs neutral) cues, than placebo-treated participants in a large interconnected bilateral cluster spanning the ventral striatum, ventral pallidum, amygdala, midbrain, and orbitofrontal cortex (voxel threshold p < 0.005; cluster corrected at p < 0.05). These results suggest that baclofen may inhibit the earliest type of drug cue-induced motivational processing-that which occurs outside of awareness-before it evolves into a less manageable state.

Computer-assisted delivery of cognitive-behavioral therapy: efficacy and durability of CBT4CBT among cocaine-dependent individuals maintained on methadone.

A previous pilot trial evaluating computer-based training for cognitive-behavioral therapy (CBT4CBT) in 77 heterogeneous substance users (alcohol, marijuana, cocaine, and opioids) demonstrated preliminary support for its efficacy in the context of a community-based outpatient clinic. The authors conducted a more definitive trial in a larger, more homogeneous sample. In this randomized clinical trial, 101 cocaine-dependent individuals maintained on methadone were randomly assigned to standard methadone maintenance or methadone maintenance with weekly access to CBT4CBT, with seven modules delivered within an 8-week trial. Treatment retention and data availability were high and comparable across the treatment conditions. Participants assigned to the CBT4CBT condition were significantly more likely to attain 3 or more consecutive weeks of abstinence from cocaine (36% compared with 17%; p<0.05, odds ratio=0.36). The group assigned to CBT4CBT also had better outcomes on most dimensions, including urine specimens negative for all drugs, but these reached statistical significance only for individuals completing the 8-week trial (N=69). Follow-up data collected 6 months after treatment termination were available for 93% of the randomized sample; these data indicate continued improvement for those assigned to the CBT4CBT group, replicating previous findings regarding its durability. This trial replicates earlier findings indicating that CBT4CBT is an effective adjunct to addiction treatment with durable effects. CBT4CBT is an easily disseminable strategy for broadening the availability of CBT, even in challenging populations such as cocaine-dependent individuals enrolled in methadone maintenance programs.

Impact of Psychiatric Comorbidity on the In-Treatment Outcomes of Cocaine-Dependent Patients in Therapeutic Communities

ABSTRACT. Background: This study aimed to explore the association between psychiatric comorbidity and treatment outcomes in therapeutic communities (TCs). Methods: A prospective longitudinal descriptive design was used. A baseline psychopathological assessment was performed within the first 15 to 20 days of treatment in the TCs. The length of treatment stay was computed for each individual. The study was conducted in the region of Andalusia (Spain). The participants were 218 cocaine-dependent individuals. Psychopathological assessment was performed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). The outcome measures were retention, defined as the time in TC treatment (number of days), and the patient's assessment upon leaving the TC. Results: The number of psychopathological comorbidities present in the last year among the patients was high (57.8%) and was associated with a worse response to treatment (P =.004). The patients with co-occurring psychiatric disorders had a decreased probability of remaining in the TCs compared with patients who only presented with substance use disorders (hazards ratio = 1.61). Conclusions: Psychiatric comorbidity predicts cocaine-dependent individuals’ likelihood of remaining in residential treatment.

Clinical Efficacy of Sertraline Alone and Augmented With Gabapentin in Recently Abstinent Cocaine-Dependent Patients With Depressive Symptoms

Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study's aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3-12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy.

An Evaluation of Substance Abuse Treatment and HIV Education on Safe Sex Practices in Cocaine Dependent Individuals.

Background. There is a strong association between crack/cocaine use and increased sexual risk behavior, but little research on the efficacy of HIV education for decreasing such behavior in crack/cocaine-addicted individuals in substance abuse treatment. Method. Datasets from two cocaine dependence trials including either one or three HIV education sessions, respectively, were analyzed for changes over time in the proportion of participants practicing safe sex. A pooled dataset from two earlier trials not offering HIV education was also analyzed. Results. We included 83 participants from the 1-session trial and 65 participants from the 3-session trial. Both sets of participants evidenced a significant increase in the proportion of participants having safe sex with casual partners. Participants in the 3-session HIV education study also evidenced a significant increase in the proportion of participants having safe sex with regular partners. In the trials without HIV education, no change in safe sex practices was found, and change in condom use was observed only among female participants. Conclusions. These findings are consistent with recommendations that HIV education/counseling should be provided to individuals in substance abuse treatment. A randomized controlled trial to confirm these results may be warranted. This trial is registered with NCT00033033, NCT00086255, NCT00015106, and NCT00015132.

Preliminary evidence for normalization of risk taking by modafinil in chronic cocaine users

Modafinil, a wake-promoting agent used to treat sleep disorders, is thought to enhance cognition. Although modafinil has shown promise as a pharmacotherapy for the treatment of cocaine dependence, it is unknown to what extent cognitive effects may play a role in such treatment. We examined the effect of modafinil on the Balloon Analogue Risk Task (BART), a behavioral measure in which higher scores are purported to reflect a greater propensity for risk-taking. Thirty cocaine dependent individuals, enrolled in a randomized clinical trial of modafinil 400mg (n=12) versus placebo (n=18), were administered the BART during the second week of inpatient treatment for cocaine dependence. A comparison cohort of healthy participants (n=19) performed the BART under similar conditions. Modafinil treatment was associated with significantly higher BART scores (p=0.01), which were comparable to scores in healthy persons. BART scores in placebo treated participants were much lower than previously reported in healthy participants, and lower than those observed in the comparison cohort. As propensity toward risk taking is typically associated with higher BART scores as well as increased risk for substance use, our findings may reflect a novel aspect of cognitive impairment related to chronic cocaine use. Notably, the low BART scores reflect highly suboptimal performance on the task, and the observed effect of modafinil may indicate a normalization of this impairment and have implications for treatment outcome.

Therapeutic infusions of ketamine: Do the psychoactive effects matter?

BackgroundSub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24h postinfusion. MethodsEight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48h were received: lorazepam (2mg) and two doses of ketamine (0.41mg/kg and 0.71mg/kg, with the former dose always preceding the latter). Infusions were followed within 15min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood's Mysticism Scale: HMS). At baseline and 24h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure). ResultsKetamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71mg/kg was associated with significantly higher HMS scores than was the 0.41mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24h postinfusion. ConclusionsThese findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.

Long-Term Reduction of Cocaine Self-Administration in Rats Treated with Adenoviral Vector-Delivered Cocaine Hydrolase: Evidence for Enzymatic Activity

A new pharmacokinetic approach treating cocaine addiction involves rapidly metabolizing cocaine before it reaches brain reward centers using mutated human butyrylcholinesterase (BChE) or cocaine hydrolase (CocH). Recent work has shown that helper-dependent adenoviral (hdAD) vector-mediated plasma CocH reduced the locomotor-activating effects of cocaine and prevented reinstatement of cocaine-seeking behavior up to 6 months in rats. The present study investigated whether hdAD-CocH could decrease ongoing intravenous cocaine (0.4 mg/kg) self-administration. The hdAD-CocH vector was injected into self-administering rats, and after accumulation of plasma CocH, there was a dramatic reduction in cocaine infusions earned under a fixed ratio 1 schedule of reinforcement that lasted for the length of the study (>2 months). Pretreatment with the selective BChE and CocH inhibitor iso-OMPA (1.5 mg/kg) restored cocaine intake; therefore, the decline in self-administration was likely due to rapid CocH-mediated cocaine metabolism. Direct measurements of cocaine levels in plasma and brain samples taken after the conclusion of behavioral studies provided strong support for this conclusion. Further, rats injected with hdAD-CocH did not experience a deficit in operant responding for drug reinforcement and self-administered methamphetamine (0.05 mg/kg) at control levels. Overall, these outcomes suggest that viral gene transfer can yield plasma CocH levels that effectively diminish long-term cocaine intake and may have potential treatment implications for cocaine-dependent individuals seeking to become and remain abstinent.

Sex Differences in Guanfacine Effects on Drug Craving and Stress Arousal in Cocaine-Dependent Individuals

Currently, no FDA-approved medication exists for the treatment of cocaine use disorder. Furthermore, as women become increasingly more at risk for the consequences of cocaine addiction, the need to establish better-tailored treatment medications is paramount. We examine the effects of the alpha2 adrenergic agonist, guanfacine HCl, on responses to stress and drug cue in a group of cocaine-dependent men and women who also abuse alcohol and nicotine. Forty early abstinent treatment-seeking cocaine-dependent males and females were randomly assigned to receive either daily placebo (12 M/7 F) or guanfacine (2 or 3 mg) (15 M/6 F) for 3 weeks. In week 4, they participated in a laboratory experiment and were exposed to three 10-min guided imagery conditions (stress/stress, cue/cue, and stress/cue), one per day, consecutively in a random, counterbalanced order. Craving, negative emotion, anxiety, and cardiovascular function were assessed at baseline, immediately following imagery exposure, and at various recovery time points. Guanfacine significantly attenuated cocaine craving, alcohol craving, anxiety, and negative emotion following exposure to all three imagery conditions in females, but not males. Guanfacine did, however, reduce sympathetic tone as well as stress and cue-induced nicotine craving and systolic blood pressure (SBP) in both males and females. These findings highlight sex-specific effects of guanfacine on drug craving, anxiety, and negative mood with significant effects in women and not men. The findings suggest further evaluation of guanfacine in the treatment of cocaine use disorder with a specific focus on sex differences in treatment response.

Reduced Frontal Brain Volume in Non-Treatment-Seeking Cocaine-Dependent Individuals: Exploring the Role of Impulsivity, Depression, and Smoking

In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM volume differences between 30 non-treatment-seeking cocaine-dependent individuals and 33 non-drug using controls using voxel-based morphometry. Additionally, within the group of non-treatment-seeking cocaine-dependent individuals, we explored the role of frequently co-occurring features such as trait impulsivity (Barratt Impulsivity Scale, BIS), smoking, and depressive symptoms (Beck Depression Inventory), as well as the role of cocaine use duration, on frontal GM volume. Smaller GM volumes in non-treatment-seeking cocaine-dependent individuals were observed in the left middle frontal gyrus. Moreover, within the group of cocaine users, trait impulsivity was associated with reduced GM volume in the right orbitofrontal cortex, the left precentral gyrus, and the right superior frontal gyrus, whereas no effect of smoking severity, depressive symptoms, or duration of cocaine use was observed on regional GM volumes. Our data show an important association between trait impulsivity and frontal GM volumes in cocaine-dependent individuals. In contrast to previous studies with treatment-seeking cocaine-dependent patients, no significant effects of smoking severity, depressive symptoms, or duration of cocaine use on frontal GM volume were observed. Reduced frontal GM volumes in non-treatment-seeking cocaine-dependent subjects are associated with trait impulsivity and are not associated with co-occurring nicotine dependence or depression.

What happens in treatment doesn't stay in treatment: cocaine abstinence during treatment is associated with fewer problems at follow-up.

Cocaine users often present to treatment with a multitude of problems typically considered addiction related; however, there is little evidence that reductions in cocaine use are followed by reductions in these problems. This study evaluated the relationship between rates of cocaine use during treatment and the level of non-cocaine life problems experienced during a 12-month period following treatment in a pooled sample of 434 cocaine-dependent individuals participating in 1 of 5 randomized controlled trials. Structural equation modeling and latent growth curve modeling were used to evaluate the relationship between frequency of cocaine use within treatment (8 or 12 weeks) and a latent construct of global problems indicated by the days of problems reported on the Addiction Severity Index across follow-up time points (1, 3, 6, and 12 months after treatment). Both a continuous latent cocaine use outcome measure (percent days abstinent, percent positive urines, and maximum days of consecutive abstinence) and a dichotomous measure of cocaine use (≥21 consecutive days of abstinence) during the treatment period were associated with frequency of cocaine use and global problems during follow-up. Overall, results indicated that greater cocaine abstinence during the treatment period was associated with higher rates of abstinence and fewer global problems experienced following treatment. This is one of the first studies to support a model that suggests addiction-related problems decrease in accordance with achieving abstinence from cocaine, thereby providing evidence that within-treatment cocaine abstinence has benefits that extend beyond the frequency of drug use.

Error-Related Brain Activity as a Biomarker for Cocaine Relapse

Addiction is characterized by the observation that substance-dependent individuals continue to use substances despite the negative consequences, such as social, interpersonal, or physical problems. The ability to adequately monitor negative consequences in behavior, referred to as error processing, is necessary for optimal behavioral performance to guide one's behavior toward one's long-term goals (eg, maintain abstinence from substance use). It has been previously reported that cocaine-dependent individuals show a decreased sensitivity to errors and this has been attributed to reduced activation in the anterior cingulate cortex (ACC; Kaufman et al, 2003). Likewise, electrophysiological research has shown that the error-related negativity (ERN)—which represents the brain's automatic detection of an error—is reduced in cocaine users compared with healthy controls (Franken et al, 2007). It has been theorized that a reduced ERN is a representation of the notion that errors are perceived as less meaningful or motivationally relevant in substance-dependent individuals (Hajcak, 2012). This may underlie their persistence of drug taking despite the clear adverse consequences. Additionally, it is conceivable that these brain dysfunctions associated with error processing also have a role in drug relapse. Error processing is typically measured using reaction time tasks with high chances to make errors, such as the Go-Nogo task or Eriksen flanker task. To examine the predictive role of error processing in drug relapse, we measured event-related potentials (ERPs) in response to an Eriksen flanker task in cocaine-dependent patients during their first week of detoxification treatment (Marhe et al, 2013). In this task, letter strings are presented and participants are required to respond as quickly and accurately as possible to a target letter. This task is frequently used to measure error processing, as participants easily make mistakes on this task. First, the results confirmed that the ERN amplitude was indeed reduced in cocaine-dependent patients as compared with non-dependent controls. Most interestingly, ERN amplitude predicted cocaine use after treatment, over and above other relevant predictors measured at baseline such as substance use severity and subjective cocaine craving. A reduced ERN at baseline was associated with a higher number of days of cocaine use at 3-month follow-up. Another recent study using functional magnetic resonance imaging found that the reduced error-related brain activity in areas such as the dorsal ACC, thalamus, and insula is associated with cocaine relapse after treatment (Luo et al, 2013). The results of both these studies indicate that cocaine-dependent patients exhibiting underactive error-related brain activity are more at risk of relapse. Error-related brain activity might serve as a biomarker helping to identify patients vulnerable for relapse already early in treatment. Although there is knowledge on the underlying brain processes of error processing (Kaufman et al, 2003; Luo et al, 2013), further investigation of the underlying neural circuitry and neurochemistry using neuroimaging and (combined) pharmacological approaches will further advance this research area. Regarding the results of Marhe et al (2013), it could be beneficial in the future to routinely assess the ERN amplitude in cocaine-dependent patients at the start of detoxification treatment. The idea to use electroencephalography (EEG) as a screening instrument has gained interest, specifically for ERP components that have good psychometric properties, such as the ERN (Hajcak, 2012; Hoffmann and Falkenstein, 2012). In addition, EEG is a noninvasive, relative inexpensive, and accessible biomarker. Therefore, it would be very feasible to use this measure in large-scale (genetic) studies. Future studies should reconfirm the association between the ERN and drug relapse and further examine the sensitivity and specificity of the ERN as a predictor of cocaine relapse. Ultimately, treatment programs could be tailored to the patient's need to improve outcomes.

Topiramate for the Treatment of Cocaine Addiction

No medication has been established as an efficacious treatment for cocaine dependence. We hypothesized that dual modulation of the mesocorticolimbic dopamine system by topiramate-a glutamate receptor antagonist and γ-aminobutyric acid receptor agonist-would result in efficacious treatment for cocaine dependence compared with placebo. To determine the efficacy of topiramate vs placebo as a treatment for cocaine dependence. Double-blind, randomized, placebo-controlled, 12-week trial of 142 cocaine-dependent adults in clinical research facilities at the University of Virginia between November 22, 2005, and July 25, 2011. Topiramate (n = 71) or placebo (n = 71) in escalating doses from 50 mg/d to the target maintenance dose of 300 mg/d in weeks 6 to 12, combined with weekly cognitive-behavioral treatment. For the efficacy period, weeks 6 to 12, the primary outcome was the weekly difference from baseline in the proportion of cocaine nonuse days; the secondary outcome was urinary cocaine-free weeks, and exploratory outcomes included craving and self- and observer-rated global functioning on the Clinical Global Impression scales. Using an intent-to-treat analysis, topiramate was more efficacious than placebo at increasing the weekly proportion of cocaine nonuse days, irrespective of whether missing data were not or were imputed conservatively to the baseline value (13.3% vs 5.3%, 95% CI for the estimated mean difference, 1.4%-14.6%, P = .02 or 8.9% vs 3.7%, 95% CI for the estimated mean difference, 0.2%-10.1%, P = .04, respectively). Topiramate also was associated, significantly more than placebo, with increasing the likelihood of urinary cocaine-free weeks (16.6% vs 5.8%; odds ratio, 3.21; 95% CI, 1.24-8.32; P = .02), as well as decreasing craving and improving observer-rated global functioning (all P < .05). Topiramate is more efficacious than placebo at increasing the mean weekly proportion of cocaine nonuse days and associated measures of clinical improvement among cocaine-dependent individuals.

Preliminary findings of the effects of rivastigmine, an acetylcholinesterase inhibitor, on working memory in cocaine-dependent volunteers

Long-term cocaine use is a risk factor for the onset of neurocognitive impairment. This study sought to determine whether the cholinesterase inhibitor rivastigmine could improve neurocognitive performance in cocaine-dependent individuals. Cocaine-dependent individuals who were not seeking treatment at the time of enrollment in the study were randomly assigned to receive placebo (n=16), rivastigmine 3mg (n=13), or rivastigmine 6mg (n=12). The baseline neurocognitive assessment, which included measures of attention/information processing (as measured by the Continuous Performance Task-II (CPT-II)), verbal learning/episodic memory (as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)), and working memory (as measured by the Dual N-Back Task), was conducted prior to the administration of study medication (Day 0). The follow-up assessment was conducted on Day 8 after the participants had received rivastigmine or placebo for 7days (Day 2-8). Rivastigmine administration significantly improved performance on one measure of working memory span (mean n-back span). This study provides additional data showing that cocaine-associated neurocognitive impairment, specifically working memory deficits, can be remediated, at least to some degree.

Demand curves for hypothetical cocaine in cocaine-dependent individuals

Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

An intrinsic connectivity network approach to insula-derived dysfunctions among cocaine users

Background: Addiction is a complex phenotype, though it consistently includes characteristics of impulsivity. A number of brain regions are suggested to be involved in cocaine addiction, including the insula, which serves diverse functions including interoceptive awareness and integration of neural signals from sensory, subcortical and frontal regions. Malfunction of this integration links impulsive behavior to the insula. Objectives: This study examines intrinsic connectivity of the insula in chronic cocaine users to investigate abnormal insular circuitry, its role in cocaine addiction, and relationships to measure of impulsivity. Methods: Cocaine-dependent individuals (n = 33) and healthy controls (n = 32) completed a resting-state fMRI scan. An intrinsic connectivity network (ICN) approach generated metrics of mean network connectivity and inter-network connectivity from fMRI data. Metrics pertaining to ICNs involving insula and other structures repeatedly involved in addiction (e.g. striatum) were selected for analysis, which included the capacity to discriminate groups. Relationships between group discriminating connectivity metrics and behavioral impulsivity were examined. Results: Models demonstrated group prediction accuracy up to 75%. Accuracy of 69% was obtained by a parsimonious model of six inter-network connectivity metrics. The inter-network connectivity between an ICN involving the anterior insula and ACC, and an ICN involving the striatum, was significantly weaker in cocaine users relative to controls. The degree of reduced inter-network connectivity was significantly related to greater non-planning impulsivity in cocaine users. Conclusions: Aberrant insula-derived intrinsic connectivity patterns are observed in cocaine users and include dysfunctions in insula to striatal connectivity, which is furthermore linked to increased impulsivity pertaining to forethought.

A preliminary investigation of Stroop-related intrinsic connectivity in cocaine dependence: associations with treatment outcomes

Background: Cocaine-dependent individuals demonstrate neural and behavioral differences compared to healthy comparison subjects when performing the Stroop color-word interference test. Stroop measures also relate to treatment outcome for cocaine dependence. Intrinsic connectivity analyses assess the extent to which task-related regional brain activations are related to each other in the absence of defining a priori regions of interest. Objective: This study examined 1) the extent to which cocaine-dependent and non-addicted individuals differed on measures of intrinsic connectivity during fMRI Stroop performance; and 2) the relationships between fMRI Stroop intrinsic connectivity and treatment outcome in cocaine dependence. Methods: Sixteen treatment-seeking cocaine-dependent patients and matched non-addicted comparison subjects completed an fMRI Stroop task. Between-group differences in intrinsic connectivity were assessed and related to self-reported and urine-toxicology-based cocaine-abstinence measures. Results: Cocaine-dependent patients vs. comparison subjects showed less intrinsic connectivity in cortical and subcortical regions. When adjusting for individual degree of intrinsic connectivity, cocaine-dependent vs. comparison subjects showed relatively greater intrinsic connectivity in the ventral striatum, putamen, inferior frontal gyrus, anterior insula, thalamus and substantia nigra. Non-mean-adjusted intrinsic-connectivity measures in the midbrain, thalamus, ventral striatum, substantia nigra, insula and hippocampus negatively correlated with measures of cocaine abstinence. Conclusion: The diminished intrinsic connectivity in cocaine-dependent vs. comparison subjects suggests poorer communication across brain regions during cognitive-control processes. In mean-adjusted analyses, the cocaine-dependent group displayed relatively greater Stroop-related connectivity in regions implicated in motivational processes in addictions. The relationships between treatment outcomes and connectivity in the midbrain and basal ganglia suggest that connectivity represents a potential treatment target.

Aberrant Disgust Responses and Immune Reactivity in Cocaine-Dependent Men

BackgroundInfectious diseases are the most common and cost-intensive health complications associated with drug addiction. There is wide belief that drug-dependent individuals expose themselves more regularly to disease-related pathogens through risky behaviors such as sharing pipes and needles, thereby increasing their risk for contracting an infectious disease. However, evidence is emerging indicating that not only lifestyle but also the immunomodulatory effects of addictive drugs, such as cocaine, may account for their high infection risk. As feelings of disgust are thought to be an important psychological mechanism in avoiding the exposure to pathogens, we sought to investigate behavioral, physiological, and immune responses to disgust-evoking cues in both cocaine-dependent and healthy men.MethodsAll participants (N = 61) were exposed to neutral and disgust-evoking photographs depicting food and nonfood images while response accuracy, latency, and skin conductivity were recorded. Saliva samples were collected before and after exposure to neutral and disgusting images, respectively. Attitudes toward disgust and hygiene behaviors were assessed using questionnaire measures.ResultsResponse times to disgust-evoking photographs were prolonged in all participants, and specifically in cocaine-dependent individuals. While viewing the disgusting images, cocaine-dependent individuals exhibited aberrant skin conductivity and increased the secretion of the salivary cytokine interleukin-6 relative to control participants.ConclusionOur data provide evidence of a hypersensitivity to disgusting stimuli in cocaine-dependent individuals, possibly reflecting conditioned responses to noningestive sources of infection. Coupled with a lack of interoception of bodily signals, aberrant disgust responses might lead to increased infection susceptibility in affected individuals.

The association between psychosis proneness and sensory gating in cocaine-dependent patients and healthy controls

This was a naturalistic study of 23 abstinent cocaine-dependent patients and 38 controls who were studied using a paired-stimulus paradigm to elicit three mid-latency auditory evoked responses (MLAERs), namely, the P50, N100, and P200. Sensory gating was defined as the ratio of the S2 amplitude to the S1 amplitude. Psychosis-proneness was assessed using four Chapman psychosis proneness scales measuring perceptual aberration, magical ideation, social anhedonia, and physical anhedonia. Omnibus correlations based upon the entire sample revealed significant and differential relationships between the MLAER components and psychosis-proneness. Social Anhedonia scale scores accounted for the largest proportion of variance in the P50 gating ratio, while Perceptual Aberration scores accounted for the largest proportion of variance in P200 gating. Psychosis proneness and sensory gating appear to be associated. In particular, poorer P50 gating is related to higher scores on the Social Anhedonia scale in healthy controls and across mixed samples of cocainede-pendent patients and controls. These findings hold significance for the further understanding of the relationship between deficient sensory gating ability and the propensity to developing psychotic symptoms in a vulnerable population like cocaine-dependent individuals.