Cocaine-dependent Individuals Research Articles

Neuropsychological profiling of impulsivity and compulsivity in cocaine dependent individuals

Research on the relative impact of trait impulsivity vs. drug exposure on neuropsychological probes of response inhibition vs. response perseveration has been posited as a valid pathway to explore the transition between impulsivity and compulsivity on psychostimulant dependence. The objectives of this study are to examine performance differences between cocaine-dependent individuals (CDI) and healthy comparison individuals (HCI) on neuropsychological probes of inhibition and perseveration and to examine the predictive impact of trait impulsivity-a proxy of premorbid vulnerability, and severity of cocaine use-a proxy of drug exposure, on CDI's performance. Forty-two CDI and 65 HCI were assessed using the UPPS-P Scale (trait impulsivity), the Stroop and go/no-go (inhibition) and revised-strategy application and probabilistic reversal tests (perseveration). CDI, compared to HCI, have elevated scores on trait impulsivity and perform significantly poorer on inhibition and perseveration, with specific detrimental effects of duration of cocaine use on perseveration. CDI have both inhibition and perseveration deficits; both patterns were broadly indicative of orbitofrontal dysfunction in the context of reinforcement learning. Impulsive personality and cocaine exposure jointly contribute to deficits in response perseveration or compulsivity.

The Obsessive Compulsive Cocaine Use Scale: Development and initial validation of a self-rated instrument for the quantification of thoughts about cocaine use

Background Craving is a hallmark of addiction and characterized by obsessive thoughts about, and compulsive urges to use, a substance. While craving is frequently thought of as primarily being a feature of acute withdrawal, there is evidence to suggest that it increases in strength over extended periods of abstinence. While several measures are available to assess acute craving states, there remains a lack of clinical measures appropriate for capturing the enduring cognitive aspects of urges to use drugs. The present study was designed to develop and validate a measure of obsessive-compulsive thoughts in cocaine-dependent individuals. Methods The proposed 14-item Obsessive Compulsive Cocaine Use Scale (OCCUS) was administered to 107 individuals: 55 participants meeting diagnostic criteria for cocaine dependence and 52 recreational users of cocaine. In addition to the OCCUS, participants also completed the Drug Abuse Screening Test, Cocaine Craving Questionnaire-Now, and Social Desirability Scale of the California Personality Inventory. Results Results of confirmatory factor analysis indicated that the OCCUS fit the two-factor structure of the Obsessive Compulsive Drinking Scale on which it was based, independently assessing the “obsessive” and “compulsive” aspects of cocaine dependence. The OCCUS demonstrated good internal consistency reliability and convergent, discriminant, and criterion validity. Conclusion The proposed measure is a promising step towards the successful capture of the long-term cognitive features of craving for cocaine via self-report, and should represent a useful tool for clinical and research use.

Effects of d-cycloserine on extinction and reinstatement of morphine-induced conditioned place preference

d-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine recognition site on the N-methyl- d-aspartate (NMDA) receptor complex, has been shown to facilitate the extinction and prevent the relapse of cocaine-induced conditioned place preference (CPP) when administered before or after each extinction trail. However, some studies have suggested that DCS does not influence or even enhance relapse of seeking behavior on cocaine self-administration (SA) in rats or cocaine-dependent individuals undergoing clinical exposure treatment. Furthermore, there are no reports on the effects of DCS and the extinction of morphine-conditioned behaviors in mice. The present study investigated the effects of DCS on extinction by exposing mice to drug-paired cues and the subsequent reinstatement of morphine-primed CPP. Our results showed that DCS at doses of 7.5, 15, and 30 mg/kg did not induce conditioned appetitive or aversive effects and DCS combined with morphine conditioning failed to affect the acquisition of morphine-induced CPP. Moreover, pretreatment with DCS (7.5, 15, and 30 mg/kg, i.p.) prior to extinction training had no significant effects on the extinction and subsequent morphine-primed reinstatement of morphine-induced CPP. These results suggested that DCS may not be a powerful adjunct for cue exposure therapy of opioid addiction. In view of differing outcomes in both preclinical and clinical studies, the potential of DCS in exposure treatment of drug-seeking behaviors should be carefully evaluated.

Effects of d-Cycloserine on Craving to Alcohol Cues in Problem Drinkers: Preliminary Findings

Background: It has been shown that the partial N-methyl-d-aspartate (NMDA) agonist d-cycloserine (DCS) facilitates exposure-based learning in humans with anxiety disorders. However, the effects of DCS on exposure to substance cues are still uncertain. Objective: The primary aim of the study was to examine the effects of DCS on exposure sessions to alcohol cues. Methods: Twenty non-treatment-seeking problem drinkers were randomly assigned to receive 50 mg of DCS or placebo 50 minutes prior to each of 3 alcohol cue exposure sessions consisting of 5 exposure trials within an 8-day period. Following this, participants underwent two test sessions without the administration of any medication. The test sessions occurred 3 and 7 days after the last cue exposure session, respectively. Dependent measures included drinking urge and heart rate and drinking urge during the test sessions. Results: Individuals who received DCS showed increased craving to alcohol cues as compared with individuals who received placebo during the first test session. No group difference in drinking urge was found during the second test session. Furthermore, the groups did not differ in heart rate at any of the assessment points. Conclusions: The results suggest that DCS may temporarily augment cue-elicited craving for alcohol. Scientific Significance: As in an earlier study with cocaine-dependent individuals, DCS appears to exhibit a different profile in problem drinkers to those with anxiety disorders. Dose, timing, arousal, and treatment motivation as considerations are discussed, as are methodological considerations and the need for additional studies in this area.

Platelet activation in chronic cocaine users: Effect of short term abstinence

Cocaine abuse increases the risk of cardiac and cerebrovascular events, such as myocardial infarction and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation has been observed. The aim of this study was to investigate the existence of platelet activation and the effect of short-term abstinence in chronic cocaine consumers. We studied 23 cocaine dependent individuals (aged 20–54 years) who met DSM-IV criteria for cocaine dependence and 20 controls. Samples were obtained at baseline, within 72 h of last drug exposure and after 4 weeks of controlled abstinence. Monocyte-platelet aggregates (MPA) were measured by flow cytometry. Plasma levels of soluble CD40L (sCD40L), Neutrophil-Activating Peptide-2 (NAP-2) and regulated on activation normal T cells expressed and secreted (RANTES) were determined by ELISA. Levels of MPA, sCD40L, NAP-2 and RANTES were significantly higher (all p < 0.05) in cocaine addicts compared to controls at baseline. All the parameters returned to values similar to the control group after 4-weeks’ abstinence. Levels of sCD40L and RANTES were associated with an index of intensity of drug consumption (p < 0.02). Our results demonstrate that cocaine use induces platelet activation which is a prominent finding after recent consumption. The persistence over time of this condition may contribute not only to acute thrombotic complications but also to the development of early-onset atherosclerotic process observed in cocaine abusers.

The Obsessive Compulsive Cocaine Scale: Assessment of factor structure, reliability, and validity

The present study assessed the factor structure, reliability, test retest, convergent validity, and predictive validity of the Obsessive Compulsive Cocaine Scale (OCCS), a newly developed questionnaire adapted from the Obsessive Compulsive Drinking Scale (OCDS). The questionnaire was administered to 189 cocaine-dependent individuals participating in two medication treatment trials for cocaine dependence. Confirmatory factor analysis of this measure revealed that it primarily assesses two factors, obsessions and compulsions. In addition, the data provided strong support for the internal consistency, test–retest reliability, predictive validity, and convergent validity of this two-factor measure. Overall, the data provide support for the psychometric strength of a modified version of the OCDS specifically designed to assess obsessive and compulsive cocaine use among those with cocaine dependence.

Increased Serum Brain-Derived Neurotrophic Factor Is Predictive of Cocaine Relapse Outcomes: A Prospective Study

Cocaine dependence is associated with high relapse rates, but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central brain-derived neurotrophic factor (BDNF) in cocaine seeking, we examined whether serum BDNF is altered in abstinent, early recovering, cocaine-dependent individuals and whether it is predictive of subsequent relapse risk. Serum samples were collected across three consecutive mornings from 35 treatment-engaged, 3-week-abstinent cocaine-dependent inpatients (17 males/18 females) and 34 demographically matched hospitalized healthy control participants (17 males/17 females). Cocaine-dependent individuals were prospectively followed on days 14, 30, and 90 posttreatment discharge to assess cocaine relapse outcomes. Time to cocaine relapse, number of days of cocaine use (frequency), and amount of cocaine use (quantity) were the main outcome measures. High correlations in serum BDNF across days indicated reliable and stable serum BDNF measurements. Significantly higher mean serum BDNF levels were observed for the cocaine-dependent patients compared with healthy control participants (p < .001). Higher serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard ratio: 1.09, p < .05), greater number of days (p < .05), and higher total amounts of cocaine used (p = .05). High serum BDNF levels in recovering cocaine-dependent individuals are predictive of future cocaine relapse outcomes and may represent a clinically relevant marker of relapse risk. These data suggest that serum BDNF levels may provide an indication of relapse risk during early recovery from cocaine dependence.

Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence

A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption.

Gender, race, and group behavior in group drug treatment

Background Group drug counseling is the primary treatment modality used to treat drug dependence in community settings in the United States. Findings from the social psychology literature suggest that gender may influence how individuals participate in groups, and that race may moderate the effects of gender on group behavior. This study examined gender, race, and their interaction as predictors of alliance, participation, self-disclosure, and receipt of advice and feedback in drug counseling groups, and explored how gender and racial differences in drug counseling group behavior related to outcome of cocaine dependence treatment. Method Ratings of group behavior were made from videotaped sessions of group drug counseling drawn from a randomized trial of treatment for cocaine-dependent individuals ( n = 438). Analyses examined the effects of race (African American or non-Hispanic White), gender, and the race by gender interaction on group behavior. Additional analyses examined race, gender, and group behavior, and interactions among these variables in predicting monthly cocaine use. Results Race and the race by gender interaction, but not gender alone, predicted many group behaviors. Non-Hispanic White women had the highest rates of self-disclosure and receipt of advice and non-positive feedback, followed by men of both races, with African American women having the lowest levels. These differences were unrelated to cross-sectional cocaine outcome. Conclusions Women, but not men, of different races acted differently in mixed-race, mixed-gender cocaine treatment groups, with African American women exhibiting less of several behaviors. Additional research on causes and consequences of these differences could inform interventions for drug-dependent women.

Association between polymorphisms in catechol‐O‐methyltransferase (COMT) and cocaine‐induced paranoia in European‐American and African‐American populations

Catechol-O-methyltransferase (genetic locus, COMT) is a major enzyme involved in catecholamine metabolism and has been associated with numerous psychiatric phenotypes. We studied COMT SNPs and haplotypes in cocaine-induced paranoia (CIP) in African-American (AA) and European-American (EA) populations. We genotyped 17 SNPs across the COMT locus in 319 AA pedigrees (848 individuals) and 302 EA pedigrees (707 individuals). Family-controlled association analyses were conducted using FBAT. We found SNP rs737865 to be nominally significantly associated in the AA family population (P = 0.05). In EAs, the best-known marker, rs4680 (Val158Met), was nominally significant in additive models (P = 0.03). SNP rs174696 also showed nominal significance in additive models (P = 0.02). We considered the three SNPs (rs737866-rs4680-rs174696) together in haplotype analysis in both family populations, using HBAT. The A-A-T haplotype was significantly associated with CIP in EAs (Z = 2.845; P = 0.0044, global P = 0.020). We then studied COMT SNPs in an additional 738 AA and 404 EA unrelated cocaine dependent individuals with and without paranoia. The A-A-T haplotype was significantly associated to CIP in the AA unrelated population (P = 0.0015). Two haplotypes, A-G-C and A-A-C, were significant in the EA unrelated population (P = 0.001 and 0.0003). We also identified rs4680 and three other SNPs, rs933271, rs5993883, and rs740603, as potentially functional variants, as predicted by a signature of positive selection in unrelated EAs and AAs. Based on our robust family-controlled and unrelated-affected analyses, we conclude that COMT is associated with CIP, possibly as a result of its role in the metabolism of dopamine and norepinephrine.

Negative mood induction normalizes decision making in male cocaine dependent individuals

Decision making is thought to play a key role in psychostimulant relapse, but very few studies have addressed the issue of how to counteract decision-making deficits in addicted individuals. According to the somatic marker framework, pervasive decision-making problems in addicted individuals may relate to abnormalities in the processing of emotional signals that work to anticipate the prospective outcomes of potential decisions. The present study was conducted to test whether the induction of different emotional states (positive, negative, or drug-related) could either normalize or further impair decision-making performance in male cocaine polysubstance-using individuals (CPSI), as indexed by the Iowa gambling task (IGT). Forty-two CPSI and 65 healthy control individuals (all males) were randomly allocated in four affective conditions using a parallel-group design. Participants in the different conditions performed the IGT during exposure to neutral, positive, negative, or drug-related sets of affective images. The results showed that the CPSI exposed to the negative affective context showed a preference for the risk-averse safe choices of the IGT and had a net performance indistinguishable from that of controls. On the other hand, CPSI exposed to positive, drug-related, and neutral contexts showed the typical pattern of disadvantageous performance in the IGT and performed significantly poorer than controls. The impact of the negative mood induction could not be explained in terms of baseline differences in decision-making skills, personality traits related to sensitivity to reward/punishment, or trait positive/negative affect. We conclude that negative mood induction can normalize decision-making performance in male CPSI, which may have important implications for the treatment of cocaine use-related disorders.

P.1.017 Chronic stress-induced impairment of memory in rats can be prevented by parallel administration of cod liver oil

Background: Preclinical evidence indicates that exposure to cocaine influences the activity of the serotonin transporter (5-HTT) as well as several 5-HT receptor subtypes. However, little is known about the relationship between the 5-HTT and 5-HT receptors following cocaine exposure in humans. Objective: We examined the relationship between platelet 5-HTT, a presynaptic 5-HT measure, and prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a postsynaptic 5-HT receptor agonist in cocaine dependent individuals. Methods: Platelet [3H] paroxetine binding sites were assayed and the m-CPP challenge test was performed in 35 African American cocaine dependent individuals and 33 controls. Clinical measures included assessments of drug use severity and depression. Results: Cocaine subjects showed reduced Bmax of [3H] paroxetine (t = 4.67, p < 0.01) and blunted PRL response to m-CPP (F = 21.86, p < 0.01) compared to controls. There was a positive correlation between Bmax and delta PRL [peak − baseline PRL] in cocaine subjects (r = 0.50, p < 0.01) but not in controls (r = 0.19). ANCOVA analyses showed that the cocaine subgroup with moderate and severe reduction in Bmax showed a greater blunting in PRL response compared to the subgroup with mild Bmax reductions (F = 9.44, p < .005). Multivariate regression models showed that the main effects as well as the interaction of Bmax and severity of cocaine use significantly contributed to impaired PRL response (F = 17.90, p < .001). Conclusions: Disturbances in serotonin transporter binding and post-synaptic 5-HT receptor function seem to be associated in cocaine-dependent subjects. Severity of cocaine use appears to mediate this relationship. Whether there is a causal association between the two measures, or cocaine has separate and independent pre- and post-synaptic effects needs to be clarified.

Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults

Background Citicoline (cytidine-5′-diphosphate) is a mononucleotide composed of ribose, cytosine, pyrophosphate, and choline, and is involved in the biosynthesis of the structural phosopholipids of cell membranes. Treatment with citicoline, improves memory in patients with dementia, and reduces damage to the brain after traumatic brain injury or stroke. Recent research has been conducted to assess whether citicoline is an effective treatment for cocaine dependence. In cocaine-dependent individuals, withdrawal from cocaine is associated with disturbed sleep, which may contribute to the high rate of relapse to cocaine use. Therefore, it is important to know the impact of citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy. Method In this double-blind, placebo-controlled trial, the effects of citicoline treatment on the sleep/wake cycles of cocaine dependent participants were assessed. The results of the current study are reported as part of a larger study, consisting of an eight-week treatment period to assess the efficacy of longer-term treatment with citicoline at decreasing cocaine consumption in cocaine-dependent polydrug using participants. Results In this non-abstinent, cocaine-dependent population, citicoline had no effect on any of the sleep parameters measured including sleep efficiency, sleep latency, total sleep time, number of waking episodes, time awake per episode, amount of time in bed spent moving, number of sleep episodes, time asleep per episode, and amount of time in bed spent immobile. Conclusions These data suggest that eight weeks of citicoline administration does not disturb sleep/wake cycles of cocaine-dependent individuals.

Frontal Hyperconnectivity Related to Discounting and Reversal Learning in Cocaine Subjects

Functional neuroimaging studies suggest that chronic cocaine use is associated with frontal lobe abnormalities. Functional connectivity (FC) alterations of cocaine-dependent individuals (CD), however, are not yet clear. This is the first study to our knowledge that examines resting FC of anterior cingulate cortex (ACC) in CD. Because ACC is known to integrate inputs from different brain regions to regulate behavior, we hypothesized that CD will have connectivity abnormalities in ACC networks. In addition, we hypothesized that abnormalities would be associated with poor performance in delayed discounting and reversal learning tasks. Resting functional magnetic resonance imaging data were collected to look for FC differences between 27 CD (5 women, age: M = 39.73, SD = 6.14 years) and 24 control subjects (5 women, age: M = 39.76, SD = 7.09 years). Participants were assessed with delayed discounting and reversal learning tasks. With seed-based FC measures, we examined FC in CD and control subjects within five ACC connectivity networks with seeds in subgenual, caudal, dorsal, rostral, and perigenual ACC. The CD showed increased FC within the perigenual ACC network in left middle frontal gyrus, ACC, and middle temporal gyrus when compared with control subjects. The FC abnormalities were significantly positively correlated with task performance in delayed discounting and reversal learning tasks in CD. The present study shows that participants with chronic cocaine-dependency have hyperconnectivity within an ACC network known to be involved in social processing and "mentalizing." In addition, FC abnormalities found in CD were associated with difficulties with delay rewards and slower adaptive learning.

Psychoticism and neuroticism predict cocaine dependence and future cocaine use via different mechanisms

BackgroundPersonality characteristics have been associated with cocaine use. However, little is known about the mechanisms through which personality could impact drug use. The present study investigated the cross-sectional and prospective relationships between personality dimensions (i.e., impulsivity, neuroticism) and problematic cocaine use. Reactivity to a pharmacological stressor as a potential mediator of the relationship between neuroticism and future cocaine use was also examined. MethodsParticipants were 53 cocaine-dependent individuals and 47 non-dependent controls. Subjects completed the Eysenck Personality Questionnaire (EPQ) at baseline and were administered i.v. corticotrophin releasing hormone (CRH; 1μg/kg). Cocaine use in the 30 days following CRH administration was measured. ResultsCocaine-dependent individuals had higher scores on the psychoticism (i.e., impulsivity, aggression; p=0.02) and neuroticism (p<0.01) scales of the EPQ than non-dependent controls. Cocaine-dependent individuals also had a greater subjective stress response to CRH than controls (p<0.01). Cocaine-dependent individuals with elevated psychoticism used significantly more cocaine over the follow-up period (p<0.05), whereas individuals with elevated neuroticism trended towards using cocaine more frequently over the follow-up (p=0.07). Finally, there was a trend for an indirect effect of neuroticism on frequency of cocaine use through subjective reactivity to CRH. ConclusionsThe findings extend past research on the association between personality and cocaine use, and suggest that motives for cocaine use may systematically vary across personality characteristics. Moreover, tailoring therapeutic interventions to individuals’ personalities may be an area that warrants further investigation.

Selective Cocaine-Related Difficulties in Emotional Intelligence: Relationship to Stress and Impulse Control

Emotional Intelligence (EI) comprises the ability to perceive, use, understand, and regulate emotions and may potentially contribute to variability in risk-related factors such as stress perception and impulse control in cocaine dependent individuals. The main objective of the current study is to better define EI in cocaine dependent individuals compared with healthy controls, using the Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT). Secondary analysis investigates the association between EI, IQ factors, perceived stress, and impulse control in both populations. Seventy-two abstinent treatment-seeking cocaine patients and 52 healthy controls were administered the MSCEIT as well as measures of IQ, perceived stress, and impulse control. Findings showed that cocaine dependent participants demonstrated highly selective EI difficulties compared with healthy controls, specifically with regard to higher-level emotional reasoning including the understanding, management, and regulation of emotion. These EI problems were associated with increased perceived stress and impulse control difficulties. IQ was significantly associated with all MSCEIT measures in the cocaine dependent participants, but not controls. Findings indicate that specific aspects of EI may be of clinical importance to cocaine dependent populations, impacting relapse-related factors such as stress dysregulation and impulse control.

Effect of Short-Term Abstinence on Cocaine-Induced Endothelial Dysfunction and Platelet Activation

AbstractAbstract 4205 Background.Cocaine abuse is associated with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. We have previously shown (Pereira et al. J Thromb Haemost 2009; 7[suppl 2]: 232a) that chronic cocaine use is associated with markers of endothelial dysfunction and platelet activation in subjects studied after recent consumption. It has been suggested that many of the adverse effects of cocaine on the vessel wall are due to its acute effects related to the sympathomimetic properties of the drug. However, from a pathogenic standpoint, we hypothesized that important pathologic consequences, such as early onset atherosclerosis and regional brain perfusion, defects, are not solely explained by the acute vasomotor actions of cocaine. Objectives.The main aim of this work was to investigate the effect of short-term abstinence on markers of endothelial injury and platelet activation in chronic cocaine consumers. methods. We studied 23 cocaine dependent individuals (aged 19–52years mean age 30 years) who met DSM-IV criteria for cocaine dependence, seeking treatment for cocaine abuse and 25 healthy controls (aged 20–49 years, mean age 31 years). Samples were obtained at admission within 72 hours of drug exposure and after 4 weeks of strict, controlled abstinence in a rehabilitation clinic.Endothelial cell damage was assessed by enumerating circulating endothelial cells (CECs) and plasma levels of soluble markers: soluble intercellular adhesion molecule (sICAM); monocyte chemoattractant protein (MCP-1), von Willebrand factor (VWF) and high-sensitivity C reactive protein (hs-CRP). Plasma levels of soluble CD40L (sCD40L), NAP-2 and RANTES were determined to demonstrate platelet activation in vivo. Results.Markers of endothelial cell damage/activation and platelet activation, were significantly higher in cocaine dependents individuals after recent consumption (baseline) as compared with the controls. The variations observed after 4 weeks drug withdrawal (post-abstinence) are shown in Table 1:CECs/mLsICAM (ng/mL)MCP-1 (ng/mL)VWF (%)sCD40L (ng/mL)NAP-2 (ng/mL)RANTES (ng/mL)Baseline62 ± 18*346 ± 140*154 ± 80*94 ± 21*1.7 ± 11.1*113 ± 53*4.1 ± 2.6*Abstinence44 ± 15**257 ± 180**166 ± 170**93 ± 22**0.98 ± 0.5**98 ± 40**2.4 ± 1.1**Controls8 ± 14219 ± 14061 ± 2678 ± 160.83 ± 0.879 ± 462.2 ± 1.6P *vs Ctrls **vs Ctrls<0.00010.00520.0030.0480.0160.0260.0070.00070.220.0040.0450.3710.1060.75 Conclusions.Our results demonstrate that cocaine use is associated to endothelial dysfunction and platelet activation which are prominent findings after recent consumption. Evidence of endothelial cell activation/damage is still present after 4 weeks of strict and controlled abstinence when markers of platelet activation returned to their baseline levels. Taken together, these observations suggest that cocaine induced-endothelial cell damage is maintained independent of the acute effect of the drug on the blood vessels. The persistence of this condition may play a role in long-term ischemic complications associated with cocaine abuse such as early onset atherosclerosis and regional brain perfusion defects. Further studies on the mechanisms underlying cocaine-induced endothelial dysfunction might provide novel strategies to improve endothelial function as part of the treatment in recently abstinent cocaine addicts. Disclosures:No relevant conflicts of interest to declare.

Assessing white matter integrity as a function of abstinence duration in former cocaine-dependent individuals

Current cocaine-dependent users show reductions in white matter (WM) integrity, especially in cortical regions associated with cognitive control that have been associated with inhibitory dysfunction. A key question is whether these white matter differences are present following abstinence from drug use. To address this, WM integrity was examined using diffusion tensor imaging (DTI) obtained on 43 cocaine abstinent patients (abstinence duration ranged between five days and 102 weeks) and 43 non-using controls. Additionally, a cross-sectional comparison separated the patients into three groups (short-term, mid-term and long-term) based upon duration of cocaine abstinence. The 43 cocaine abstinent patients showed lower fractional anisotropy (FA) in the left anterior callosal fibers, left genu of the corpus callosum, right superior longitudinal fasciculus, right callosal fibers and the superior corona radiata bilaterally when compared against non-using controls. Higher FA in the cocaine abstinent patients was observed in the splenium of the corpus callosum and right superior longitudinal fasciculus. Differences between the cocaine abstinent groups were observed bilaterally in the inferior longitudinal fasciculus, right anterior thalamic radiation, right ventral posterolateral nucleus of the thalamus, left superior corona radiata, superior longitudinal fasciculus bilaterally, right cingulum and the WM of the right precentral gyrus. The results identified WM differences between cocaine abstinent patients and controls as well as distinct differences between abstinent subgroups. The findings suggest that specific white matter differences persist throughout abstinence while other, spatially distinct, differences discriminate as a function of abstinence duration. These differences may, therefore, represent brain changes that mark recovery from addiction.

Decision-Making Deficits Linked to Real-life Social Dysfunction in Crack Cocaine-Dependent Individuals

Crack cocaine-dependent individuals (CCDI) present abnormalities in both social adjustment and decision making, but few studies have examined this association. This study investigated cognitive and social performance of 30 subjects (CCDI × controls); CCDI were abstinent for 2 weeks. We used the Social Adjustment Scale (SAS), Wisconsin Card Sorting Test (WCST), and Iowa Gambling Task (IGT). Disadvantageous choices on the IGT were associated with higher levels of social dysfunction in CCDI, suggesting the ecological validity of the IGT. Social dysfunction and decision making may be linked to the same underlying prefrontal dysfunction, but the nature of this association should be further investigated.

Relationship between gender and psychotic symptoms in cocaine-dependent and methamphetamine-dependent participants

It has been well documented that cocaine and methamphetamine use can lead to the onset of psychotic symptoms similar to schizophrenia. However, the research and literature on gender differences and stimulant-induced psychosis have been mixed. The primary aim of this study was to investigate gender differences in the reporting of psychotic symptoms in cocaine- versus methamphetamine-dependent individuals. Participants were recruited from the Los Angeles, California, community via radio and newspaper advertisements. All met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for cocaine or methamphetamine dependence, and all reported either methamphetamine or cocaine as their primary drug of abuse. During a screening interview, participants answered questions from the Psychotic Symptom Assessment Scale, which characterizes various types of psychotic symptoms during drug use ("while high") or during periods of nonuse ("while abstinent"). Participants included 42 cocaine-dependent individuals (27 men, 15 women) and 43 methamphetamine-dependent individuals (25 men, 18 women). Among cocaine users, there were no significant differences between men and women with regard to ethnicity, years of use, route of administration, and amount used in the past week, though they differed significantly with regard to age (P = 0.029). In the "while abstinent" condition, women were significantly more likely than men to report experiencing auditory hallucinations (13% vs 0%, respectively; P = 0.050) and tactile hallucinations (20% vs 0%; P = 0.016), whereas men were more likely to report delusions of grandeur (48% vs 6%; P = 0.006). During the "while high" condition, women were significantly more likely than men to report delusions of grandeur (13% vs 0%, respectively; P = 0.050), tactile hallucinations (33% vs 0%; P = 0.001), and olfactory hallucinations (13% vs 0%; P = 0.050). Among methamphetamine users, there were no significant differences between men and women with regard to age, ethnicity, years of use, route of administration, or amount used in the past week. In the "while abstinent" condition, women were significantly more likely than men to report feeling that something was wrong with the way a part of their body looked (72% vs 32%, respectively; P = 0.009), olfactory hallucinations (39% vs 8%; P = 0.010) and dressing inappropriately (22% vs 0%; P = 0.010). During the "while high" condition, women were more likely than men to report delusions of grandeur (33% vs 16%, respectively; P = 0.030), paranoia (50% vs 16%; P = 0.017), and tactile hallucinations (61% vs 32%; P = 0.050). The findings of the present study revealed that cocaine- and methamphetamine-dependent women were more likely than their male counterparts to report experiencing various psychotic symptoms. This information may be useful for clinicians and mental health professionals, who should take these symptoms into account as potential barriers that may impede effective treatment.