Associations between behavioral disinhibition and cocaine use history in individuals with cocaine dependence

Background

Behavioral disinhibition has been suggested as both a cause and consequence of substance use disorders. Many studies examining associations between behavioral disinhibition and substance use history have focused on individuals with alcohol dependence or non-dependent college students. In the present study, the relationship between behavioral disinhibition and cocaine use history in individuals with cocaine dependence is examined.

Methods

Forty-six non-treatment-seeking cocaine-dependent men and women completed impulsivity (Barratt Impulsiveness Scale; BIS) and novelty seeking (Temperament and Character Inventory; TCI) questionnaires at the baseline visit of an ongoing study. Unadjusted, and adjusted for gender and age, Pearson correlations were calculated between BIS, TCI, and cocaine use variables from the Structured Clinical Interview for DSM-IV and Timeline Follow-back (age of onset, quantity/frequency of past 30 day cocaine use).

Results

As expected, elevated motor impulsivity and novelty seeking were each associated with younger age of dependence onset. Also, individuals with lower levels of persistence on the TCI reported more days of cocaine use over the previous month. Unexpectedly, increased novelty seeking and attentional impulsivity were associated with fewer days of cocaine use and less money spent on cocaine, respectively. Controlling for age and gender did not substantially change the pattern of observed associations.

Conclusions

The present study provides preliminary evidence for associations between behavioral disinhibition and cocaine use history in cocaine-dependent individuals. Given our relatively small sample size and the correlational nature of our findings, further research is needed to replicate and extend our results.     

Trait impulsivity and prefrontal gray matter reductions in cocaine dependent individuals

Background

Impulsivity is thought to play a key role in cocaine addiction onset and progression; therefore, we hypothesized that different facets of impulsive personality may be significantly associated with brain structural abnormalities in cocaine-dependent individuals.

Methods

Thirty-eight cocaine-dependent individuals and 38 non-drug using controls completed the UPPS-P scale (measuring five different facets of impulsivity: sensation seeking, lack of premeditation, lack of perseverance, and positive and negative urgency) and were scanned on a 3T MRI scanner. We used whole-brain voxel-based morphometry analyses (VBM) to detect differences in gray matter (GM) and white matter (WM) volumes between cocaine users and controls, and to measure differences in the way that impulsivity relates to GM and WM volumes in cocaine users vs. controls.

Results

Cocaine-dependent individuals had lower GM volumes in a number of sections of the orbitofrontal cortex, right inferior frontal gyrus, right insula, left amygdala and parahippocampal gyrus, temporal gyrus, and bilateral caudate. They also had lower WM volumes in the left inferior and medial frontal gyrus, superior temporal gyrus, right anterior cingulate cortex, insula and caudate. There was a positive correlation between trait impulsivity and GM volume in the left inferior/middle frontal gyrus of cocaine-dependent individuals, a pattern directly opposed to the association in controls. Conversely, in cocaine users lack of premeditation was negatively correlated with GM volume in the insula and the putamen.

Conclusions

Trait impulsivity may influence cocaine dependence by impacting its neurobiological underpinnings in frontostriatal systems.     

The impact of craving and impulsivity on aggression in detoxified cocaine-dependent patients

Patients with substance use disorders are frequently associated with impulsivity that may underlie elevated levels life-threatening types of behavior, including aggression. In addition, craving is a prominent feature of addiction and appears to be closely related to impulsivity. This study assessed the unique contribution of cocaine craving and impulsivity in predicting aggression by means of correlational and mediational analyses. Forty inpatient detoxified cocaine-dependent patients and 40 matched healthy controls were enrolled. These participants filled out the Obsessive Compulsive Drug Use Scale, the Dickman Impulsivity Inventory, and the Aggression Questionnaire. The patient group showed elevated levels of impulsivity and aggression as compared with the control group. Although cocaine craving is positively correlated with both impulsivity and aggression, craving did not mediate the relationship between both constructs. It is concluded that craving does not have an impact on the relationship between impulsivity and trait aggression in this patient sample.     

Cognitive impulsivity in cocaine and heroin polysubstance abusers

RATIONALE: Chronic abuse of psychoactive substances produces significant deficits in executive control functions (ECF). These deficits are prominent in different domains associated with cognitive impulsivity, including response inhibition and decision-making. The extent and nature of these deficits may depend on the principal substance of abuse. OBJECTIVES: To analyse response inhibition and decision-making performance in abstinent polysubstance abusers (PSA) of cocaine and heroin, and healthy participants. METHODS: We used univariate and multivariate analyses of variance to compare the performances of cocaine and heroin PSA and healthy controls on several well-validated measures of response inhibition (Stroop, 5-Digit Test and Go/No Go Task) and decision-making (Iowa Gambling Task). Post-hoc exploratory analyses of the results from the Go/No Go task were conducted to examine specific effects of task switching on the pattern of omission/commission errors in the PSA groups. RESULTS: Cocaine but not heroin PSA showed significant deficits on several measures of response inhibition, when compared to controls. Reversal of task contingencies in the Go/No Go task primarily altered the commission error rate in cocaine PSA, and the omission error rate in heroin PSA. In contrast, both cocaine and heroin PSA showed poorer performance on decision-making compared to controls. CONCLUSIONS: Assuming the relevance of polysubstance involvement, cocaine abuse seems to differentially correlate with motor impulsivity skills, while both substances seem to be equally linked to the inability to decide advantageously in complex decision-making tasks. Possible discrepancies in the neurological and psychological effects of these drugs are discussed.     

The impact of impulsivity on cocaine use and retention in treatment

To determine whether impulsivity was related to severity of drug use and treatment outcome, 50 cocaine dependent subjects underwent baseline measures of severity of current cocaine use and the Barratt Impulsiveness Scale (BIS-11). The hypothesis of the study was that there would be a significant correlation between impulsivity and cocaine use severity. As predicted, there was a significant correlation between BIS-11 total scores and self-reported average daily cocaine use as well as cocaine withdrawal symptoms. A subset of 35 patients underwent a 12-week double-blind placebo controlled trial of buspirone and group therapy. Subjects with high baseline impulsivity remained in the study a significantly shorter period than did subjects with lower baseline impulsivity. This study shows that impulsivity is a significant predictor of cocaine use and treatment retention, and suggests the need for targeting impulsivity in cocaine dependence treatment.     

Moderators of delay tolerance in treatment-seeking cocaine users

A substantial amount of attrition in cocaine dependence treatment studies occurs between the initial telephone contact and the first evaluative clinic visit. While decreasing the wait to first visit can significantly reduce pre-intake attrition (PIA), little is known about other factors that moderate delay tolerance for first clinic visit. The current report uses data from 833 subjects who completed a first-contact telephone interview prior to an intake evaluation visit for cocaine use treatment research. Hierarchical logistic regression was used to assess three successive models to predict PIA, with the most inclusive model testing interactions between delay interval and seven predictors: age, gender, treatment motivation, recency of cocaine, alcohol, and tobacco use, and self-reported depression. Consistent with previous reports, greater delay to first clinic visit predicted PIA. However, no evidence for the moderating role of the selected factors was found. Overall, the utility of the logistic models, built on basic demographic and psychiatric factors, was poor, as evaluated using receiver-operator characteristic curves. Alternative factors must be examined to identify predictors that will increase probability of initial enrolment in cocaine-dependence clinical trials.     

Psychometric properties of the Barratt Impulsiveness Scale in patients with gambling disorders,hypersexuality, and methamphetamine dependence

Although the Barratt Impulsiveness Scale (BIS; Patton, Stanford, & Barratt, 1995) is a widely-used self-report measure of impulsivity, there have been numerous questions about the invariance of the factor structure across clinical populations (Haden & Shiva, 2008, 2009; Ireland & Archer, 2008). The goal of this article is to examine the factor structure of the BIS among a sample consisting of three populations exhibiting addictive behaviors and impulsivity: pathological gamblers, hypersexual patients, and individuals seeking treatment for methamphetamine dependence to determine if modification to the existing factors might improve the psychometric properties of the BIS. The current study found that the factor structure of the BIS does not replicate in this sample and instead produces a 12-item three-factor solution consisting of motor-impulsiveness (5 items), non-planning impulsiveness (3 items), and immediacy impulsiveness (4 items). The clinical utility of the BIS in this population is questionable. The authors suggest future studies to investigate comparisons with this modified version of the BIS and other impulsivity scales such as the UPPS-P Impulsive Behavior Scale in clinical populations when assessing disposition toward rash action.     

Alcohol, cannabis, ecstasy and cocaine: drugs of reasoned choice amongst young adult recreational drug users in England

This paper describes the current drugs consumption patterns of a cohort of English young adults who have been tracked, longitudinally, since they were fourteen. It compares their tobacco, alcohol and illicit drugs consumption at 22 years (n=465) with when they were 18 years (n=529) using self-report questionnaires and in-depth interviews (n=86). It further explores whether, as a very drugwise/experienced sample of adolescents, this cohort are now beginning to settle down and reduce their substance use. The results suggest that any reductions in recreational drug use are likely to be delayed beyond traditional markers. The cohort have largely maintained their consumption habits with rates for current tobacco smoking (35.5%), regular drinking (82.3%), on-going drug involvement (past year, any drug, 52.1%) and more regular use (past month, any drug, 31.2%) being almost identical to their rates at 18 years. Current drug involvement is increasingly dominated by cannabis however. A minority continue to use ecstasy. LSD and amphetamine use have declined but cocaine trying (lifetime prevalence 5.9% at 18 years up to 24.6%) and use have increased dramatically. Mixing and combining substances is commonplace. Hedonistic motives for these substance use patterns remain but are now joined by the need to use psycho-active repertoires ‘sensibly’ to relax and reduce the stresses of the working week. This style of recreational drug use by generally conforming adults offers a severe challenge to current national drugs strategy.     

A comparison of motivations for use among users of crack cocaine and cocaine powder in a sample of simultaneous cocaine and alcohol users

This study examined the motivations for using cocaine and alcohol comparing those who primarily smoked crack and those who primarily used cocaine powder when using simultaneously with alcohol. Motivations examined included: 1) to cope with a negative affect, 2) enhancement, 3) to be social and 4) to conform. The research design was a cross-sectional study in which clients in treatment for cocaine and alcohol problems completed a self-administered questionnaire about their substance use. Among those who primarily smoked crack or snorted cocaine when also using alcohol (n = 153), there were 93 participants who reported primarily snorting cocaine and 60 participants who primarily reported smoking crack. Bivariate analyses found that those who primarily smoked crack reported lower social motivations to use alcohol and cocaine. When adjusting for other covariates in a multivariate analysis, social motivation was still significantly different between groups. Additionally, those who primarily smoked crack were more likely to be older, report higher cocaine dependence severity, be unemployed and were less likely to have completed some post-secondary education, than those who primarily snorted cocaine. No differences were found in enhancement, coping or conformity motivations between the two groups. These results suggest that simultaneous cocaine and alcohol use may have social importance to those who primarily snort cocaine, but that this importance is less evident to those who smoke crack. Consequently, future studies examining motivations for simultaneous cocaine and alcohol use should distinguish between different routes of cocaine administration.     

Impulsivity is associated with treatment non-completion in cocaine- and methamphetamine-dependent patients but differs in nature as a function of stimulant-dependence diagnosis

Greater impulsivity, assessed by the Barratt Impulsiveness Scale–11 (BIS-11) and Stroop interference scores, has been associated with treatment completion in cocaine-dependent patients. This study evaluated the relationships among impulsivity, stimulant-dependence diagnosis, and treatment completion. Six sites evaluating 12-step facilitation for stimulant abusers obtained the BIS-11 and Stroop from 182 methamphetamine- and/or cocaine-dependent participants. Methamphetamine-dependent, relative to cocaine-dependent, participants evidenced significantly greater BIS-11 non-planning and total scores. There was a trend for poorer response inhibition, measured by the Stroop, in cocaine-dependent, relative to methamphetamine-dependent, participants. Accounting for other factors related to treatment completion, BIS-11 motor score, assessing the tendency to act without thinking, predicted treatment completion for both cocaine-dependent and methamphetamine-dependent patients. These results suggest that methamphetamine-dependent and cocaine-dependent patients may have different impulsivity profiles but that the BIS-11 may be useful in identifying both methamphetamine-dependent and cocaine-dependent patients who are at risk for treatment non-completion.     

Impulsivity differences in recreational cannabis users and binge drinkers in a university population

Background

Recreational cannabis use and alcohol binge drinking are the most common drug consumption patterns in young adults. Impulsivity and several psychopathological signs are increased in chronic drug users, but the implications of recreational use are still poorly understood.

Methods

We evaluated impulsivity, sensation-seeking traits, impulsive decision-making, inhibitory control and possible symptoms of depression, anxiety and psychosis in three groups of young university adults: recreational cannabis users (N = 20), alcohol binge drinkers (N = 22) and non-drug users (N = 26).

Results

The cannabis and binge drinking groups had increased scores for impulsivity and sensation-seeking traits. Both groups also exhibited increased impulsive decision-making on the two-choice task and the Iowa Gambling task; however, only the cannabis group was significantly different from the non-drug group regarding inhibitory control (Go/No-Go and Stop tasks). The cannabis and binge drinking groups did not show differences in the psychopathological symptoms evaluated.

Conclusions

Our observations of this population of non-dependent drug users are consistent with the increased impulsivity traits and behaviors that have been described previously in chronic drug abusers. In this study, compared to no drug use, the recreational use of cannabis was associated with a major dysfunction of the different facets of impulsive behaviors. However, alcohol binge drinking was related only to impulsive decision-making. These results suggest that impulsivity traits and behaviors are present not only in chronic drug abusers but also in recreational drug users. Future work should continue to investigate the long-term effects of these common consumption patterns on various impulsive behaviors and psychopathological symptoms.     

Predicting response to opiate antagonists and placebo in the treatment of pathological gambling

Rationale  Although opiate antagonists have shown promise in the treatment of pathological gambling (PG), individual responses vary. No studies have systematically examined predictors of medication treatment outcome in PG. Understanding clinical variables related to treatment outcome should help generate treatment algorithms for PG. Objective  We sought to identify clinical variables associated with treatment outcome in PG subjects receiving opiate antagonists. Materials and methods  Two hundred eighty-four subjects [137 (48.2%) women] with DSM-IV PG were treated in one of two double-blind placebo-controlled trials (16 weeks of nalmefene or 18 weeks of naltrexone). Gambling severity was assessed with the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) with positive response defined as ≥35% reduction in PG-YBOCS score for at least 1 month by study endpoint. Depression, anxiety, and psychosocial functioning were included in stepwise logistic regression analyses designed to identify clinical factors independently associated with treatment response. Results  The clinical variable most strongly associated with a positive response to an opiate antagonist was a positive family history of alcoholism (p = 0.006). Among individuals receiving higher doses of opiate antagonists (i.e., nalmefene 50 or 100 mg/day or naltrexone 100 or 150 mg/day), intensity of gambling urges (PG-YBOCS urge subscale) was associated with a positive response on a trend level (p = 0.036). Among individuals receiving placebo, younger age was associated, on a trend level, with positive treatment outcome (p = 0.012). Conclusions  A family history of alcoholism appears to predict response to an opiate antagonist in PG. Future research is needed to identify specific factors (e.g., genetic) mediating favorable responses.     

A preliminary study of the neural effects of behavioral therapy for substance use disorders

Background

The mechanisms by which behavioral therapies for substance use disorders (SUDs) exert their effects and the components of treatment that contribute most to substance use outcome remain unclear. Disruptions to aspects of impulse control and attention have been hypothesized to contribute to the development and maintenance of addiction; moreover, alterations in these processes may underlie responses to treatment.

Methods

Individuals participating in a randomized clinical trial evaluating computer-assisted cognitive behavioral therapy (CBT) for substance abuse participated in fMRI Stroop before and after treatment. A non-substance-using comparison group performed the same task under test–retest conditions.

Results

The patient group demonstrated decreased Stroop-related BOLD signal in regions including the anterior cingulate, inferior frontal gyrus and midbrain at post-treatment relative to pre-treatment, and displayed a greater decrease in the subthalamic nucleus and surrounding regions compared to healthy controls following test–retest.

Conclusions

Behavioral therapies may be associated with reduction in substance use and effects on neural systems involved in cognitive control, impulsivity, motivation and attention.     

Identifying the facets of impulsivity that explain the relation between ADHD symptoms and substance use in a nonclinical sample

Adults with attention-deficit/hyperactivity disorder (ADHD) are at higher risk to use substances than their nonclinical peers. Increased levels of impulsivity are generally thought to contribute to their increased levels of risk. Impulsivity is a multifaceted construct, however, and little research to date has attempted to identify which facets of impulsivity contribute to the increased rates of substance abuse among individuals with ADHD. The current study examined the relation among ADHD symptom clusters (i.e., hyperactivity/impulsivity and inattention), substance use rates (i.e., alcohol use, nicotine use, and marijuana use), and personality processes associated with impulsive behavior in a group of young adults. Participants were 361 undergraduate students. Both symptom clusters were positively associated with rates of substance use. Specifically, hyperactive/impulsive symptoms were associated with alcohol and nicotine use, and inattentive symptoms were associated with alcohol use. Several pathways from hyperactive/impulsive symptoms to alcohol, nicotine, and marijuana use via specific facets of impulsivity were identified. These findings have implications for understanding the relation between ADHD symptoms and substance use, as well as clinical implications for preventing and treating substance use problems in individuals with symptoms of ADHD.     

Differences in impulsivity and risk-taking propensity between primary users of crack cocaine and primary users of heroin in a residential substance-use program

Crack cocaine use is more associated with impulsivity and a propensity to take risks than heroin use, yet no studies have examined this relationship in the absence of acute drug effects. The current study examined impulsivity (using the Delay Discounting Task) and risk-taking propensity (using the Balloon Analogue Risk Task) across independent groups of primary crack cocaine users with minimal heroin use (n = 16) and primary heroin users with minimal crack cocaine use (n = 11) in residential treatment, with all participants drug abstinent during participation. Crack cocaine users evidenced greater levels of impulsivity and risk-taking propensity, with only the difference in impulsivity persisting after controlling for age and gender. These data hold potential theoretical importance in understanding differences between crack cocaine and heroin users, as the findings cannot be attributed solely to acute pharmacological drug effects.     

Effects of periadolescent versus adult cocaine exposure on cocaine conditioned place preference and motor sensitization in mice

Rationale Age of initial exposure to addictive substances is inversely proportional to risk of developing drug dependence. There is debate, however, as to whether intake at a young age causes dependency or whether young people who experiment with addictive substances are predisposed to dependency by other factors.Objectives We tested the relationship between cocaine exposure at two different ages in mice and the development of subsequent drug-seeking behavior to test for age-specific exposure effects.Methods We performed dose-response analysis of cocaine conditioned place preference (CPP) and locomotor activity in periadolescent and adult C57Bl/6J mice. In addition, we pretreated periadolescent and adult C57Bl/6J mice with cocaine or saline in the home cage or a drug-associated context, and then examined their behavior in a biased CPP procedure in adulthood.Results Dose-response relationships were similar between the two age groups. In the pretreatment experiments, we observed locomotor sensitization during the pretreatment in periadolescent but not adult mice. We also observed an enhanced aversion to the non-preferred side of the chamber in periadolescent mice compared to adult mice, which was alleviated by cocaine association with that side. Third, we observed that after further conditioning in adulthood, there were no pretreatment-specific effects.Conclusions Our results are consistent with a vulnerable brain hypothesis for responses to cocaine based on our findings that periadolescent mice exhibit greater locomotor sensitization to cocaine, and greater baseline anxiety responses that are alleviated by cocaine exposure compared to adult mice.     

A MAOA gene*cocaine severity interaction on impulsivity and neuropsychological measures of orbitofrontal dysfunction: Preliminary results

Background

Based on previous evidence of a MAOA gene*cocaine use interaction on orbitofrontal cortex volume attrition, we tested whether the MAOA low activity variant and cocaine use severity are interactively associated with impulsivity and behavioral indices of orbitofrontal dysfunction: emotion recognition and decision-making.

Methods

72 cocaine dependent individuals and 52 non-drug using controls (including healthy individuals and problem gamblers) were genotyped for the MAOA gene and tested using the UPPS-P Impulsive Behavior Scale, the Iowa Gambling Task and the Ekman's Facial Emotions Recognition Test. To test the main hypothesis, we conducted hierarchical multiple regression analyses including three sets of predictors: (1) age, (2) MAOA genotype and severity of cocaine use, and (3) the interaction between MAOA genotype and severity of cocaine use. UPPS-P, Ekman Test and Iowa Gambling Task's scores were the outcome measures. We computed the statistical significance of the prediction change yielded by each consecutive set, with ‘a priori’ interest in the MAOA*cocaine severity interaction.

Results

We found significant effects of the MAOA gene*cocaine use severity interaction on the emotion recognition scores and the UPPS-P's dimensions of Positive Urgency and Sensation Seeking: Low activity carriers with higher cocaine exposure had poorer emotion recognition and higher Positive Urgency and Sensation Seeking.

Conclusion

Cocaine users carrying the MAOA low activity show a greater impact of cocaine use on impulsivity and behavioral measures of orbitofrontal cortex dysfunction.     

Natural reward-related learning in rats with neonatal ventral hippocampal lesions and prior cocaine exposure

Rational Psychostimulant injections in rats have been shown to alter future performance in natural reward conditioning. These effects may represent a persistent impact of drugs on neurocircuits that interface cognitive and motivational processes, which may be further altered in neuropsychiatric conditions that entail increased addiction vulnerability.Objective This study investigated whether a rat model of schizophrenia with cocaine addiction vulnerability shows altered natural reward conditioning with or without prior cocaine exposure.Methods Adult rats with SHAM or neonatal ventral hippocampal lesions were given cocaine (15 mg/kg per day for 5 days) or saline injections, followed 7 days later by natural reward-conditioned learning. Over ten daily sessions, water-restricted rats were assessed for durations of head entries into a magazine during random water presentations, a conditioning stimulus phase predictive of the water reward, and an inappropriate phase when conditioning stimuli were absent and reward presentation would be delayed.Results Over repeated sessions, lesioned and SHAM rats showed similar reductions in total magazine entry durations, with similar increases in the allocations of entry times during the water presentation. However, lesioned rats, especially those exposed to cocaine, demonstrated reduced allocations of magazine entry times during the conditioning stimulus phase, and increased allocations during the inappropriate phase.Conclusions Intact natural reward motivation accompanied by deficient learning of complex contingencies to guide efficient reward approach may represent a form of impulsivity as an addiction vulnerability trait marker in an animal model of schizophrenia.     

Escalation of food-maintained responding and sensitivity to the locomotor stimulant effects of cocaine in mice

Escalation of drug self-administration is a consequence of extended drug access and is thought to be specifically related to addiction, but few studies have investigated whether intake of non-drug reinforcers may also escalate with extended-access. The goal of these studies was to determine the effects of limited and extended-access to food reinforcers on behavioral and pharmacological endpoints in mice. In distinct groups, responding on a lever was maintained by liquid reinforcement, or nose-poke responses were maintained by sucrose pellets or liquid food in sessions lasting 1 h (limited-access) or 10 h (extended-access). The reinforcing strength of each food, as well as reinforcer-associated cues, was tested before and after extended-access using a progressive ratio (PR) schedule, and locomotor activity in response to novelty and increasing doses of cocaine was assessed in an open field setting in all animals after access to food reinforcers. Escalation of lever-pressing behavior reinforced by liquid food, but not nose-poke behavior reinforced by liquid food or sucrose pellets, was observed across successive extended-access sessions. A concomitant increase in the reinforcing strength of liquid food and its associated cues was apparent in mice that escalated their responding, but not in mice that did not escalate. Finally, extended reinforcer access leading to behavioral escalation was accompanied by an increased sensitivity to the psychostimulant effects of cocaine compared to limited-access. These findings indicate that behavioral escalation can develop as a consequence of extended-access to a non-drug reinforcer, although both the nature of the reinforcer (liquid versus solid food) and the topography of the operant response (lever versus nose-poke) modulate its development. These data also suggest that some of the behavioral and pharmacological corrolaries of behavioral escalation observed following extended-access to drug self-administration may not be due to drug exposure, but rather, may result from basic behavioral processes which underlie operant responding maintained by appetitive stimuli.