Dependent Cocaine Users Research Articles

Endocannabinoids and related lipids linked to social exclusion in individuals with chronic non-medical prescription opioid use

Opioid-related overdose deaths are still on the rise in North America, emphasizing the need to better understand the underlying neurobiological mechanisms regarding the development of opioid use disorder (OUD). Recent evidence from preclinical and clinical studies indicate that the endocannabinoid system (ECS) may play a crucial role in stress and reward, both involved in the development and maintenance of substance use disorders. Animal models demonstrate a specific crosstalk between the ECS and the endogenous opioid system. However, translational studies in humans are scarce. Here, we investigated basal plasma levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyglycerol (2-AG), and eight endocannabinoid-related lipids, including oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), as well as whole blood fatty acid amide hydrolase (FAAH) activity in chronic non-medical prescription opioid users (NMPOU; n = 21) compared to opioid-naïve healthy controls (n = 29) considering age, sex, and cannabis use as potential confounders. Additionally, the association of endocannabinoids and related lipids with the participants’ response to experimentally induced social exclusion was examined. We found significantly elevated basal AEA, OEA, and PEA levels in NMPOU compared to controls, but no differences in FAAH activity, 2-AG, or other endocannabinoid-related lipids. Within NMPOU, higher AEA levels were associated with lower perception of social exclusion. Robust positive correlations within N-acylethanolamines (i.e., AEA, OEA, and PEA) indicate strong metabolic associations. Together with our recent findings of elevated basal 2-AG levels in dependent cocaine users, present results indicate substance-specific alterations of the ECS that may have implications in the search for novel therapeutic interventions for these populations.

Alterations of Stress-Related Glucocorticoids and Endocannabinoids in Hair of Chronic Cocaine Users.

BackgroundPrevious research in animals and humans has demonstrated a potential role of stress regulatory systems, such as the hypothalamic-pituitary-adrenal (HPA) axis and the endocannabinoid (eCB) system, in the development of substance use disorders. We thus investigated alterations of HPA and eCB markers in individuals with chronic cocaine use disorder by using an advanced hair analysis technique.MethodsWe compared hair concentrations of glucocorticoids (cortisone, cortisol) and the eCBs 2-arachidonylglycerol, anandamide (AEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA) between 48 recreational cocaine users (RCU), 25 dependent cocaine users (DCU), and 67 stimulant-naïve controls. Self-reported substance use and hair concentrations of substances were also assessed.ResultsSignificantly higher concentrations of hair cortisone were found in RCU and DCU compared with controls. Hair concentrations of OEA and PEA were significantly lower in DCU compared with RCU and controls. Additionally, within cocaine users, elevated cocaine hair concentration was a significant predictor for increased glucocorticoid and decreased OEA hair levels. Moreover, higher 3,4-methyl​enedioxymethamphetamine hair concentration was correlated with elevated cortisone and AEA, OEA, and PEA levels in hair within cocaine users, whereas more self-reported cannabis use was associated with lower eCBs levels in hair across the total sample.ConclusionOur findings support the hypothesis that the HPA axis and eCB system might be important regulators for substance use disorders. The mechanistic understanding of changes in glucocorticoid and eCB levels in future research might be a promising pharmacological target to reduce stress-induced craving and relapse specifically in cocaine use disorder.

Psychiatric symptoms and expression of glucocorticoid receptor gene in cocaine users: A longitudinal study

BackgroundChronic cocaine users (CU) display reduced peripheral expression of the glucocorticoid receptor gene (NR3C1), which is potentially involved in stress-related psychiatric symptoms frequently occurring in CU. However, it is unknown whether psychiatric symptoms and lower NR3C1 expression are related to each other and whether reduction of drug consumption reverse them. MethodAt baseline, NR3C1 mRNA expression was measured in 68 recreational CU, 30 dependent CU, and 68 stimulant-naïve controls. Additionally, the Revised Symptom Checklist (SCL-90R) and the Barratt Impulsiveness Scale (BIS) were assessed. At a one-year follow-up, the association between change in NR3C1 expression and psychiatric symptoms was examined in 48 stimulant-naïve controls, 19 CU who increased and 19 CU who decreased their consumption. At both test sessions, cocaine concentrations in hair samples were determined. Mixed-effects models were used to investigate how changes in drug use intensity affect severity of psychiatric symptoms and NR3C1 expression over time. ResultsAt baseline, recreational and dependent CU displayed elevated impulsivity and considerable symptom burden across most of the SCL-90R subscales. Time-group interaction effects were found for several impulsivity scores, SCL-90R Global Severity Index, Paranoid Thoughts, and Depression subscales as well as for NR3C1 expression. Pairwise comparisons showed that decreasing CU specifically improved in these SCL-90R subscales, while their NR3C1 expression was adapted. Finally, changes in NR3C1 expression were negatively correlated with changes in impulsivity but not SCL-90R scores. ConclusionOur findings suggest that NR3C1 expression changes and some psychiatric symptoms are reversible upon reduction of cocaine intake, thus favouring abstinence-oriented treatment approaches.

Stable self-serving personality traits in recreational and dependent cocaine users.

Chronic cocaine use has been associated with impairments in social cognition, self-serving and antisocial behavior, and socially relevant personality disorders (PD). Despite the apparent relationship between Machiavellianism and stimulant use, no study has explicitly examined this personality concept in cocaine users so far. In the frame of the longitudinal Zurich Cocaine Cognition Study, the Machiavellianism Questionnaire (MACH-IV) was assessed in 68 recreational and 30 dependent cocaine users as well as in 68 psychostimulant-naïve controls at baseline. Additionally, three closely related personality dimensions from the Temperament and Character Inventory (TCI)–cooperativeness, (social) reward dependence, and self-directedness–and the screening questionnaire of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) were acquired. At the one-year follow-up, 57 cocaine users and 48 controls were reassessed with the MACH-IV. Finally, MACH-IV scores were correlated with measures of social cognition and interaction (cognitive/emotional empathy, Theory-of-Mind, prosocial behavior) and with SCID-II PD scores assessed at baseline. Both recreational and dependent cocaine users showed significantly higher Machiavellianism than controls, while dependent cocaine users additionally displayed significantly lower levels of TCI cooperativeness and self-directedness. During the one-year interval, MACH-IV scores showed high test-retest reliability and also the significant gap between cocaine users and controls remained. Moreover, in cocaine users, higher Machiavellianism correlated significantly with lower levels of cooperativeness and self-directedness, with less prosocial behavior, and with higher cluster B PD scores. However, Machiavellianism was not correlated with measures of cocaine use severity (r<-.15). Both recreational and dependent cocaine users display pronounced and stable Machiavellian personality traits. The lack of correlations with severity of cocaine use and its temporal stability indicates that a Machiavellian personality trait might represent a predisposition for cocaine use that potentially serves as a predictor for stimulant addiction.

Retrospective Monitoring of Long-Term Recreational and Dependent Cocaine Use in Toenail Clippings/Scrapings as an Alternative to Hair

Toenails were assessed as an alternative matrix to hair for retrospective monitoring of cocaine consumption of recreational and dependent users. Results/methodology: Toenail clippings, scrapings and hair samples from recreational and dependent cocaine users were analyzed for cocaine and metabolites. Dependent users displayed significantly higher concentrations in hair and toenail samples compared to recreational users. Cocaine abstinence could be monitored in hair and toenail samples. One postmortem fingernail was analyzed in layers to investigate the cocaine and metabolite concentration profile. Highest concentrations were observed in the dorsal layer, being indicative of contamination. Having led to comparable results, toenails may be an alternative for retrospective monitoring of cocaine consumption/abstinence. Hair should remain the first choice for assessment of temporal evidence of drug intake.

Modulation of risky choices in recently abstinent dependent cocaine users: a transcranial direct-current stimulation study.

Previous neurobiological and neuropsychological investigations have shown that risk-taking behaviors and addictions share many structural and functional aspects. In particular, both are characterized by an irresistible need to obtain immediate rewards and by specific alterations in brain circuits responsible for such behaviors. In this study, we used transcranial direct-current stimulation over the dorsolateral prefrontal cortex (DLPFC) of two samples of subjects (18 dependent cocaine users and 18 control subjects) to investigate the effects of left and right cortical excitability on two risk tasks: (1) the balloon analog risk task (BART) and (2) the game of dice task (GDT). All subjects randomly received a left anodal/right cathodal stimulation (LAn+), a right anodal/left cathodal stimulation (RAn+), and a sham (placebo) stimulation each run at least 48 h apart. Participants were asked to perform the BART and the GDT immediately before and after each stimulation. Our results reveal that the activation of the DLPFC (left and right) results in a reduction of risky behaviors at the BART task both in controls subjects and cocaine dependent users. The effect of tDCS on GDT, instead, is more complex. Cocaine users increased safe behavior after right DLPFC anodal stimulation, while risk-taking behavior increased after left DLPFC anodal stimulation. Control subjects’ performance was only affected by the anodal stimulation of the right DLPFC, resulting in an increase of safe bets. These results support the hypothesis that excessive risk propensity in dependent cocaine users might be due to a hypoactivation of the right DLPFC and an unbalance interhemispheric interaction. In conclusion, since risky decision-making seems to be, at least in part, responsible for maintenance and relapse of addiction, we argue that a neuromodulation-based approach could represent a valuable adjunct in the clinical treatment of addiction.

Characteristics and course of dependence in cocaine-dependent individuals who never used alcohol or marijuana or used cocaine first.

Cocaine users typically try alcohol or marijuana before cocaine, but this ordering of substance use initiation is not universal. Characterizing cocaine-dependent users who deviate from the typical sequence may be informative for understanding the multiple pathways to cocaine dependence. Data were drawn from cocaine-dependent participants (N = 6,333; 41% female) in a multisite study of the genetics of substance dependence who completed in-person structured psychiatric interviews. Participants were categorized with respect to alcohol or marijuana use as (a) never used, (b) used cocaine first, or (c) first used at the same age as or after first cocaine use. The association of a range of demographic, psychiatric, and childhood risk factors with sequences of initiation and the association of those sequences with indicators of dependence course (e.g., severity) were investigated in a series of regression analyses. Women and non-European Americans were overrepresented in the atypical sequence groups. The atypical sequence groups also differed from the typical sequence groups with respect to rates of other substance use disorders. Sequences of substance use initiation were largely unrelated to other psychiatric disorders or childhood risk factors. Individuals who never used marijuana had a lower severity of dependence. Although only a minority of dependent cocaine users deviate from the typical sequence of substance use initiation, several characteristics distinguish them from those who follow the typical sequence. Findings underscore the diversity in pathways to cocaine dependence.

Altered social and non-social decision-making in recreational and dependent cocaine users

Maladaptive decision-making is assumed to be a core feature of cocaine addiction. Indeed, numerous studies have reported deficits in non-social decision-making tasks and reward-related impulsivity in dependent cocaine users. However, social decision-making has not been examined in cocaine users yet. Moreover, it is unknown if even recreational and non-dependent cocaine use is linked to decision-making deficits. Therefore, we investigated whether recreational and dependent cocaine users exhibit alterations in social and non-social decision-making. The performance of healthy controls (n = 68), recreational cocaine users (n = 68) and dependent cocaine users (n = 30) in classical decision-making paradigms (Iowa Gambling Task, Delay Discounting) and in social interaction paradigms (Distribution Game, Dictator Game) was assessed. Decisions in the social interaction tasks of both cocaine user groups were more self-serving compared with controls as cocaine users preferred higher monetary payoffs for themselves. In the Iowa Gambling Task, only dependent cocaine users were more likely to choose disadvantageous card decks, reflecting worse decision-making. They were also more likely to choose immediate smaller rewards over larger delayed rewards in the Delay Discounting task. Our results imply that both recreational and dependent cocaine users are more concerned with their own monetary gain when interacting with another person. Furthermore, primarily dependent cocaine users are less foresighted and more impulsive regarding immediate reward. Overall, social interaction deficits are already present in recreational users, while non-social decision-making deficits occur predominantly in dependent cocaine users. Thus, social interaction training and cognitive remediation strategies may improve treatment success and quality of life in cocaine dependence.

Cognitive dysfunctions in recreational and dependent cocaine users: role of attention-deficit hyperactivity disorder, craving and early age at onset

Dependent cocaine users consistently display cognitive deficits but cognitive performance of recreational cocaine users has rarely been investigated. To examine whether cognitive performance is impaired in relatively pure recreational and dependent cocaine users. The cognitive performance of recreational (n = 68) and dependent cocaine users (n = 30) was compared with the performance of stimulant-naive controls (n = 68) employing an extensive neuropsychological test battery. Moreover, the impact of attention-deficit hyperactivity disorder (ADHD) symptoms, craving and early age at onset was analysed. Dependent cocaine users display broad cognitive impairments in the domains of attention, working memory, declarative memory and executive functions. The performance of recreational cocaine users in all four domains was intermediate between that of controls and dependent users and they displayed significant deficits foremost in the domains of attention and working memory. In addition, ADHD symptoms, craving and age at onset were important modulators of cognitive function in cocaine users. Cognitive deficits occur at a recreational and non-dependent level of cocaine use. Cocaine use and ADHD seem to have mutually aggravating effects on cognitive impairment.

Impaired emotional empathy and related social network deficits in cocaine users

Chronic cocaine users consistently display neurochemical and functional alterations in brain areas involved in social cognition (e.g. medial and orbitofrontal cortex). Although social functioning plays a crucial role in the development and treatment of drug dependence, studies investigating social cognition in cocaine users are lacking. Therefore, we investigated mental perspective taking ('theory of mind') and emotional and cognitive empathy in recreational (RCU) and dependent (DCU) cocaine users. Furthermore, we related these measures to real-life indicators of social functioning. One-hundred cocaine users (69 RCU, 31 DCU) and 68 stimulant-naïve healthy controls were tested with the Multifaceted Empathy Test (MET), Movie for the Assessment of Social Cognition (MASC) and Reading the Mind in the Eyes Test (RMET). The Social Network Questionnaire was conducted to assess social network size. Furthermore, participants provided information on committed criminal offenses. RCU and DCU showed less emotional empathy compared to controls (MET), whereas cognitive empathy was not impaired (MET, RMET). Additionally, DCU made more errors in mental perspective taking (MASC). Notably, cocaine users committed more criminal offenses and displayed a smaller social network and higher cocaine use was correlated with less social contacts. Diminished mental perspective taking was tentatively correlated with more intense cocaine use as well. Finally, younger age of onset of cocaine use was associated with more pronounced empathy impairment. In conclusion, social cognition impairments in cocaine users were related to real-life social functioning and should therefore be considered in therapy and prevention strategies.

Differences in self-reported and behavioral measures of impulsivity in recreational and dependent cocaine users

BackgroundDependent cocaine users consistently display increased trait impulsivity on self-report questionnaires and less consistently exhibit elevated motor impulsivity in some behavioral tasks. However, trait and behavioral impulsivity measures have rarely been investigated in recreational users. Therefore, we examined self-reported trait and motor impulsivities in recreational and dependent cocaine users to clarify the role of impulse control in cocaine addiction and non-dependent cocaine use. MethodsWe investigated relatively pure recreational (n=68) and dependent (n=30) cocaine users, as well as psychostimulant-naïve controls (n=68), with self-report questionnaires (Barratt Impulsiveness Scale 11; Temperament and Character Inventory) and behavioral tasks (Rapid Visual Information Processing Task; Stop-Signal Task). ResultsCompared with controls, recreational and dependent cocaine users displayed higher trait impulsivity and novelty seeking scores on self-report questionnaires. Trait impulsivity scores were strongly associated with an increased number of symptoms of depression and attention deficit hyperactivity disorder and correlated significantly with long-term cocaine intake parameters. By contrast, none of the behavioral motor impulsivity measures showed significant group effects or correlated with cocaine use parameters. The correlations among the self-report measures were high, but self-reports were scarcely correlated with behavioral task measures. ConclusionsThese findings suggest that relatively pure cocaine users already display increased trait impulsivity at a recreational level of use. However, the results do not indicate any cocaine-related elevation of behavioral impulsivity in terms of motor or response inhibition. In summary, our data imply that elevated trait impulsivity is not a specific feature of dependent cocaine use.

Blue–yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users

Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.

Quitting Drugs: Quantitative and Qualitative Features

According to the idea that addiction is a chronic relapsing disease, remission is at most a temporary state. Either addicts never stop using drugs, or if they do stop, remission is short lived. However, research on remission reveals a more complex picture. In national epidemiological surveys that recruited representative drug users, remission rates varied widely and were markedly different for legal and illegal drugs and for different racial/ethnic groups. For instance, the half-life for cocaine dependence was four years, but for alcohol dependence it was 16 years, and although most dependent cocaine users remitted before age 30, about 5% remained heavy cocaine users well into their forties. Although varied, the remission results were orderly. An exponential growth curve closely approximated the cumulative frequency of remitting for different drugs and different ethnic/racial groups. Thus, each year a constant proportion of those still addicted remitted, independent of the number of years since the onset of dependence.

Increased Sensorimotor Gating in Recreational and Dependent Cocaine Users Is Modulated by Craving and Attention-Deficit/Hyperactivity Disorder Symptoms

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system.

P.6.d.010 Social and non-social decision-making in occasional and dependent cocaine users

Social learning theory, as originally proposed by Albert Bandura, followed 2000 years of intellectual inquiry into the determinants of human behavior. Reciprocal determinism is a central component of this theory and proposes that human behavior is determined by functional relationships between (1) personal factors, (2) the external environment, and (3) the behavior itself. Using this model, drug addiction can be viewed as resulting from the functional relationships between an individual’s personal characteristics, social environment, and drug-centric behaviors. In other words, addiction can be viewed as a chronically evolving biopsychosocial disorder, encompassing dimensions that are both internal and external to the individual. Effective treatment interventions should thus target all nodes of the model and the functional relationships between them, and they must constantly evolve with the progression of the disorder. An argument is thus constructed that emphasizes the need for an organized structure of metacontingencies, operating within an individual’s social environment, that targets the functional relationships between the factors that drive drug use. Optimally, these metacontingencies would operate within socially connected individuals who have the power to control the functional relationships that influence drug use, the vested interest to monitor individual and collective outcomes, the skills to determine what moment-to-moment decisions are needed to influence behavioral change, and the relative permanence necessary to carry through with the implementation of new strategies to produce outcomes that are cumulatively significant.

Cocaine-related medical and trauma problems

The purpose of this retrospective study was to describe the spectrum of medical and trauma complications associated with self-reported cocaine use. Patient databases of 23 emergency departments were searched for consultations related to cocaine use between January 2007 and December 2008. The population included 569 men (84.4%) and 105 women (15.6%): 505 (74.9%) patients were nondependent cocaine users and 169 (25.1%) were dependent cocaine users. The majority of patients (63.8%) used other drugs in combination with cocaine. Psychiatric symptoms were most frequently reported (60.9%), followed by cardiopulmonary (38.2%), gastrointestinal (22.5%), neurological (20.8%) and constitutional (17.2%) symptoms. Of psychiatric complaints, anxiety was the most common (31.5%). Sex-adjusted and age-adjusted odds ratio (OR) showed that palpitations were associated within 12 h of cocaine use [OR 2.05; 95% confidence interval (CI): 1.12-3.76], and psychotic symptoms (OR 3.05; 95% CI: 1.02-9.18) and hallucinations (OR 7.50; 95% CI: 1.12-50.31) were associated within more than 12 h of the use of cocaine. In a comparison of dependent and nondependent cocaine users, after adjusting for age and sex, cardiopulmonary symptoms (OR 1.56; 95% CI: 1.08-2.24) and paranoia (OR 2.14; 95% CI: 1.08-4.24) were associated with nondependent use of cocaine, and lethargy (OR 7.14; 95% CI: 1.55-35.56) was associated with dependent use of cocaine. The primary cause of trauma was unintentional injuries (32.4%). Sex-adjusted and age-adjusted OR showed a major risk for unintentional injuries with nondependent use of cocaine (OR 6.17; 95% CI: 1.38-42.29). The study shows that cocaine users experience diverse symptoms and may present with a wide range of physical findings.

Novelty seeking as a predictor of treatment retention for heroin dependent cocaine users

This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant relationships with overall retention were entered into a logistic regression analysis. In addition, using a survival analysis, all variables with significant relationships with time to drop-out were entered into a multivariate proportional hazards regression with time dependent covariates. Results demonstrated that although high novelty seekers, in comparison to low novelty seekers, were more likely to drop-out by the end of treatment, they had higher retention rates during the early phases of treatment. It is suggested that buprenorphine and contingency management were viewed by participants as novel treatment components and thus facilitated high novelty seekers’ success early in treatment. If replicated, results suggest that inclusion of novel treatment components might facilitate retention among this at-risk group.