Cocaine-dependent Patients Research Articles

INTERDEPENDENT GROUP CONTINGENCY MANAGEMENT FOR COCAINE‐DEPENDENT METHADONE MAINTENANCE PATIENTS

Contingency management (CM) for drug abstinence has been applied to individuals independently even when delivered in groups. We developed a group CM intervention in which the behavior of a single, randomly selected, anonymous individual determined reinforcement delivery for the entire group. We also compared contingencies placed only on cocaine abstinence (CA) versus one of four behaviors (CA, treatment attendance, group CM attendance, and methadone compliance) selected randomly at each drawing. Two groups were formed with 22 cocaine-dependent community-based methadone patients and exposed to both CA and multiple behavior (MB) conditions in a reversal design counterbalanced across groups for exposure order. The group CM intervention proved feasible and safe. The MB condition improved group CM meeting attendance relative to the CA condition.

A pilot study of community-friendly manual-guided drug counseling

Therapist training manuals that are more “community friendly” are needed to facilitate effectiveness testing and dissemination of treatments to community based setting. The aim of the current project was to create revised versions of individual drug counseling (IDC) and group drug counseling (GDC) treatment manuals for cocaine dependence and to conduct a preliminary study of their effectiveness. After changing the format and context of existing drug counseling manuals to have greater ease of use in the community, draft manuals were given to 23 community-based counselors for their feedback. Final versions were then used in a pilot randomized clinical trial involving 41 cocaine-dependent patients who received 3 months of either IDC + GDC or GDC-alone treatment. Counselors implemented the new treatment manuals with acceptable levels of adherence and competence. Outcome results indicated that substantial change in drug use was evident, but the amount of abstinence obtained was limited.

Impaired Reproduction of Three-Dimensional Objects by Cocaine-Dependent Subjects

Impaired Reproduction of Three-Dimensional Objects by Cocaine-Dependent Subjects

CLINICAL STUDY: Cocaine craving is associated with electrophysiological brain responses to cocaine‐related stimuli

Several studies show that substance dependence disorders are characterized by an enhanced processing of substance-related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electrophysiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine-dependent patients. These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders.

Pretreatment Brain Activation During Stroop Task Is Associated with Outcomes in Cocaine-Dependent Patients

Cognitive behavioral and related therapies for cocaine dependence may exert their effects, in part, by enhancing cognitive control over drug use behavior. No prior studies have systematically examined the neural correlates of cognitive control as related to treatment outcomes for cocaine dependence. Twenty treatment-seeking cocaine-dependent individuals performed a Stroop color-word interference task while undergoing functional magnetic resonance imaging (fMRI) prior to initiating treatment. The primary outcome measures were percent of urine drug screens negative for cocaine, percent days abstinent, and treatment retention. Correlations between regional brain activation during Stroop task performance and treatment outcome measures were analyzed. During Stroop performance, individuals activated brain regions similar to those reported in nonaddicted individuals, including the anterior cingulate cortex, dorsolateral prefrontal cortex, parietal lobule, insula, and striatum. Activations at treatment onset correlated differentially with specific outcomes: longer duration of self-reported abstinence correlated with activation of ventromedial prefrontal cortex, left posterior cingulate cortex, and right striatum; percent drug-free urine screens correlated with striatal activation; and treatment retention correlated with diminished activation of dorsolateral prefrontal cortex. A modest correlation between Stroop effect and treatment retention was found. The functions of specific brain regions underlying cognitive control relate differentially to discrete outcomes for the treatment of cocaine dependence. These findings implicate neurocircuitry underlying cognitive control in behavioral treatment outcome and provide insight into the mechanisms of behavioral therapies for cocaine dependence. They also suggest neural activation patterns during cognitive control tasks are more sensitive predictors of treatment response than behavioral measures.

The role of the alliance and techniques in predicting outcome of supportive-expressive dynamic therapy for cocaine dependence.

We examine the complex relations among therapeutic alliance, adherence to Supportive-Expressive Therapy (SET), therapist competence, and their interactions in predicting change in drug use. Experts rated early therapy sessions of cocaine dependent patients (n 108) randomized to SET as part of the Collaborative Cocaine Treatment Study. Moderate adherence to SET and competent delivery of SET were separately associated with poorer outcome. Further, strong alliance combined with low levels of SET adherence was associated with a better outcome than moderate or high levels. Moreover, the usage of nonprescribed techniques (i.e., Individual Drug Counseling [IDC]) by SET therapists predicted better outcome in a subsample (n 36), and SET patients receiving high levels of IDC adherence had less predicted drug use compared with those with high levels of SET techniques. Overall results may suggest that decreasing cocaine use through straightforward drug counseling techniques instead of trying to help patients understand the reasons for their use is a better initial road to recovery.

Attentional deficits in cocaine-dependent patients: Converging behavioral and electrophysiological evidence

Although there are several reports of patients with cocaine dependence displaying cognitive deficits, the nature of their information processing deficits is not well characterized. In the present study, the attentional performance of cocaine-dependent patients ( n = 14) was examined and compared with that of healthy control individuals ( n = 15). Attention was assessed using an auditory oddball event-related task as well as the Continuous Performance Test (CPT, Identical Pairs version). The cocaine-dependent group displayed P300 amplitude reduction compared to controls. The group difference in P300 response latency did not reach significance. On the CPT, the cocaine-dependent patients displayed significantly poorer discriminability and greater errors of commission than the controls. There was a positive correlation between performance on the oddball event-related task and performance on the CPT. This investigation provides converging behavioral and electrophysiological evidence of attentional deficits in cocaine-dependent patients.

The Search for Medications to Treat Stimulant Dependence

Progress in understanding the neurobiology of stimulant dependence has enabled researchers to identify medications whose pharmacological effects suggest that they might help patients initiate abstinence or avoid relapse. Several of these medications and a vaccine have shown encouraging results in controlled clinical trials with cocaine-dependent patients. The search for a medical treatment for methamphetamine dependence started more recently, due to the later emergence of this epidemic, but at least one candidate medication has shown promise in early clinical testing. Treatment approaches that combine efficacious medications and empirically proven behavioral interventions, such as voucher-based reinforcement therapy, will almost certainly produce the best results.

Modafinil: A Useful Medication for Cocaine Addiction? Review of the Evidence from Neuropharmacological, Experimental and Clinical Studies

Cocaine addiction is a chronic relapsing disorder associated with severe medical and psychosocial complications. However, there are no approved medications for cocaine dependent individuals. Modafinil, a medication that differs chemically and pharmacologically from other central nervous system stimulants, has been suggested to be potentially useful for this complex disorder. The present paper aims to critically review the published evidence from laboratory and clinical studies on modafinil for cocaine addiction, including discussion of its pharmacological characteristics and how it may relate with cocaine neurobiology. Whilst its exact mechanism of action remains to be elucidated, different neurotransmitter systems have been implicated, including modulation on dopamine, glutamate/GABA, noradrenaline and the hypocretin/orexin system, but it is possible that modafinil acts by a synergistic combination of mechanisms. With a favourable pharmacokinetic profile, it appears to have a low abuse potential. Laboratory and clinical studies provide consistent, albeit preliminary, evidence of the potential usefulness of modafinil for cocaine dependent patients. Not only there is no evidence of pharmacokinetic interactions between modafinil and cocaine, but in addition cocaine induced euphoria and cardiovascular effects appear to be attenuated by modafinil. Furthermore, modafinil has been shown to decrease cocaine self-administration. In addition, modafinil treated patient are more likely to achieve protracted abstinence than placebo treated patients. However, further research is needed to confirm these findings.

Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor

Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons.Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users.In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers.BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users (1).These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users.1) Angelucci F, Ricci V, Pomponi M, Conte G, Mathe AA, Tonali P, Bria P. Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor. J Psychopharmacol. 2007 Aug 22

A Pet imaging study of the effects of modafinil and topiramate on brain mechanisms underlying cue-induced cocaine craving and dependence in cocaine-dependent and methadone maintained cocaine-dependent patients

A Pet imaging study of the effects of modafinil and topiramate on brain mechanisms underlying cue-induced cocaine craving and dependence in cocaine-dependent and methadone maintained cocaine-dependent patients

CLINICAL STUDY: Adrenocorticotropic hormone and cortisol plasma levels directly correlate with childhood neglect and depression measures in addicted patients

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been reported to be involved in vulnerability to alcohol and drug dependence in humans, possibly underlying both addictive behaviour and depression susceptibility. The aim of the present study was to investigate the possible interactions between childhood adverse experiences, depressive symptoms and HPA axis function in addicted patients, in comparison with healthy control. Eighty-two abstinent heroin or cocaine dependent patients and 44 normal controls, matched for age and sex, completed the symptoms Check List-90 (SCL-90), measuring depressive symptoms, and the Childhood Experience of Care and Abuse Questionnaire. Blood samples were collected to determine adrenocorticotropic hormone (ACTH) and cortisol basal plasma levels at 8:00 and 8:30 a.m. Addicted individuals showed significantly higher neglect and depression scores and ACTH-cortisol plasma levels respect to control subjects. Depression scores at SCL-90 in addicted patients positively correlated with plasma ACTH and cortisol values. In turn, plasma ACTH levels were directly associated with childhood neglect measures, reaching statistical significance with 'mother-neglect' scores. Plasma cortisol levels were related to 'father antipathy' among cocaine addicts. These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may have a persistent effect on HPA axis function as an adult, partially contributing, together with genetic factors and other environmental conditions, to both depressive traits and substance abuse neurobiological vulnerability.

Cocaine Withdrawal Symptoms Identify “Type B” Cocaine‐Dependent Patients

Recent studies of substance dependence typologies briefly show that multivariate systems originally developed for identifying subtypes of alcoholics, such as Babor's Type A and B system, may also be valid in abusers of other substances, such as cocaine. Type B patients are characterized by an earlier onset of addiction and more severe symptoms of their addiction, psychopathology, and impulsivity. The Type B classification has also been associated with deficits in serotonergic function. We have found that patients who exhibit more severe cocaine withdrawal symptoms, as measured by scores on the Cocaine Selective Severity Assessment (CSSA), have poor treatment outcome and share many characteristics with "Type B" patients. In this paper, we review baseline characteristics of cocaine-dependent patients from several recently completed outpatient cocaine dependence treatment trials to assess the association of cocaine withdrawal symptom severity and the Type B profile. Identifying subtypes of cocaine-dependent patients may improve our ability to treat cocaine dependence by targeting treatments for specific subtypes of patients. We examined the ability of the CSSA scores to capture Type B characteristics in cocaine dependence by analyzing a series of cocaine medication trials that included 255 cocaine-dependent subjects. High CSSA scores at baseline were associated with a history of violent behavior, a family history of substance abuse, antisocial personality disorder, higher addiction severity, and co-morbid psychiatric diseases. Patients with high CSSA scores are also more likely to meet criteria for Type B (Type II) cocaine dependence. Identifying Type B cocaine-dependent patients may help to develop targeted psychosocial or pharmacological treatments for these difficult-to-treat patients.

Self-efficacy for cocaine abstinence: Pretreatment correlates and relationship to outcomes

Little research has been conducted on the relationship of self-efficacy at treatment entry to individual differences or to treatment outcome for patients with cocaine dependence. Those relationships were examined in 163 cocaine-dependent patients in a residential treatment program using two measures of self-efficacy administered in the first week of treatment: beliefs about success in quitting in general and confidence about not using in 11 cocaine-specific high-risk situations. The most robust correlates of self-efficacy were greater desire to stop using and lower urge to use in high-risk situations. Age, depressive symptoms, cognitive functioning, recent substance use, and past success with quitting also correlated with self-efficacy. Both measures of self-efficacy predicted quantity and frequency of cocaine use and abstinence at 3 but not 6 months after treatment after controlling pretreatment cocaine use. Results suggest that treatments should target self-efficacy in cocaine-dependent patients.

Alpha synuclein protein levels are increased in serum from recently abstinent cocaine abusers

Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. Recent studies have shown increased alpha synuclein protein expression in serum of alcoholic patients that is linked with severity of alcohol craving. The aim of this study was to analyze the serum levels of alpha synuclein in healthy subjects and in recently abstinent cocaine abusers. Alpha synuclein protein expression was measured by enzyme-linked immunosorbent assay in serum specimens obtained from 38 recently abstinent cocaine dependent patients and 14 control subjects. The presence of cocaine dependence disorder was based on the Structured Clinical Interview (DSM-IV). Drug severity was assessed by the Addiction Severity Index ratings and composite measures. Scores of the intensity and frequency of cocaine craving episodes were obtained from the Minnesota Cocaine Craving Questionnaire. The serum concentrations of alpha synuclein in cocaine dependent patients were significantly higher as compared with age-matched drug-free controls ( p < 0.001). Alpha synuclein levels in blood were significantly correlated with the intensity ( r = 0.60, p < 0.001) and frequency ( r = 0.64, p < 0.001) of cocaine craving and with 30 days of cocaine use in the prior month before entry to treatment ( r = 0.56, p < 0.005). However, there was no correlation between the serum protein levels of alpha synuclein and age in either group. This report is the first demonstration of altered alpha synuclein levels in peripheral blood from cocaine abusers. These data agree with previous reports in postmortem brain of cocaine abusers and provide support for an association between alpha synuclein and cocaine dependence.

Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor

Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs may alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons. In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers. Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users. BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users. These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users.

Barreras de accesibilidad al tratamiento: diferencias entre adictos a la heroína y adictos a la cocaína de la Comunidad Valenciana

Objectives This study aimed at assessing the main factors why cocaine and heroin dependent patients delay their entrance to treatment in drug abuse specific resources in the Autonomous Region of Valencia, as well as to identify whether differences are found according to the substance that caused the treatment demand. Method Five hundred and thirty nine patients from Addictive Behaviours Units (UCA) were interviewed. A survey was conducted including items about previous demanded treatment and barriers of accessibility to treatment in specific ambulatory centres. Results The «Unawareness of illness and related problems» axis (mean ± sd, 2.29 ± 0.639) obtained the highest scores, while the «Treatment extrinsecal factors» axis obtained the lowest scores (1.51 ± 0.417). Male cocaine addicts scored higher in «Unawareness of illness and related problems» and «Treatment extrinsec factors» axis, and male heroin addicts had higher scores in «Resistance to change» and «Treatment intrinsec factors». The «Stigmatization and environment response» axis did not register significative differences among the different user profiles. Conclusions Barriers such as logistic, financial and administrative were considered less important by evaluated individuals. It is required to develop training programs addressed to health practitioners to detect the problem and to improve the motivation to change of drug dependent patients.

Efficacy of central nervous system stimulant treatment for cocaine dependence: a systematic review and meta‐analysis of randomized controlled clinical trials

To evaluate the efficacy of central nervous system (CNS) stimulants compared with placebo for the treatment of cocaine dependence. A systematic review and meta-analysis was carried out. Bibliographic databases were searched, reference lists of retrieved studies were hand-searched and the first authors of each study were contacted. All randomized controlled clinical trials (RCCT) comparing the efficacy of any CNS stimulant with placebo in cocaine-dependent patients were included. Quantitative data synthesis was performed for each single CNS stimulant and for all CNS stimulants. Nine RCCT met the inclusion criteria. These RCCT included 640 patients and compared five CNS stimulants: mazindol, dextroamphetamine, methylphenidate, modafinil and bupropion with placebo. No CNS stimulant improved study retention [RR = 0.94 (0.81-1.09)] or cocaine use [RR = 0.90 (0.79-1.02)]. An exploratory analysis using indirect estimations of cocaine use showed that the proportion of cocaine-positive urine screens was lower with dexamphetamine than with placebo [RR = 0.73 (0.60-0.90)] and that all CNS stimulants pooled together also suggested a significant decrease of cocaine use [RR = 0.87 (0.77-0.99)]. Data on craving could not be meta-analysed due to heterogeneity, but no RCCT found differences in cocaine craving between active drug and placebo except one, whose outcome favoured dexamphetamine. No serious adverse event (AE) was reported. Average of AE-induced dropouts was low and was greater for CNS stimulants than placebo: 4.4% versus 1.3% (P = 0.03). The main outcomes of this study do not support the use of CNS stimulants for cocaine dependence. Nevertheless, secondary analyses provide some hopeful results that encourage further research with these drugs, mainly with dexamphetamine and modafinil.

Contingency management in cocaine abusers: A dose-effect comparison of goods-based versus cash-based incentives.

Goods-based contingency management interventions (e.g., those using vouchers or prizes as incentives) have demonstrated efficacy in reducing cocaine use, but cost has limited dissemination to community clinics. Recent research suggests that development of a cash-based contingency management approach may improve treatment outcomes while reducing operational costs of the intervention. However, the clinical safety of providing cash-based incentives to substance abusers has been a concern. The present 16-week study compared the effects of goods-based versus cash-based incentives worth $0, $25, $50, and $100 on short-term cocaine abstinence in a small sample of cocaine-dependent methadone patients (N = 12). A within-subject design was used; a 9-day washout period separated each of 8 incentive conditions. Higher magnitude ($50 and $100) cash-based incentives (checks) produced greater cocaine abstinence compared with the control ($0) condition, but a magnitude effect was not seen for goods-based incentives (vouchers). A trend was observed for greater rates of abstinence in the cash-based versus goods-based incentives at the $50 and $100 magnitudes. Receipt of $100 checks did not increase subsequent rates of cocaine use above those seen in control conditions. The efficacy and safety data provided in this and other recent studies suggest that use of cash-based incentives deserves consideration for clinical applications of contingency management, but additional confirmation in research using larger samples and more prolonged periods of incentive delivery is needed.

Effects of major depressive disorder and attention-deficit/hyperactivity disorder on the outcome of treatment for cocaine dependence

Co-occurring psychiatric disorders have been associated with poor prognosis among substance-dependent patients, but few studies have examined this association among patients with cocaine dependence (CD). We compared baseline characteristics and treatment outcome between cocaine-dependent patients with major depressive disorder (MDD; n = 66), those with attention-deficit/hyperactivity disorder (ADHD; n = 53), and those with CD without comorbid disorders (CD alone; n = 48) who had been randomized to the placebo arms of clinical trials with venlafaxine, methylphenidate, and gabapentin, respectively. The three groups differed significantly in racial makeup, with more Caucasians and Hispanics among patients with MDD and those with ADHD but more African Americans among those with CD alone. The groups did not differ significantly in treatment retention, with retention rates ranging from 42% to 47%; neither did they differ in the rates of achieving 2 consecutive weeks of urinalysis-confirmed abstinence, with rates ranging from 40% to 50%. Using logistic regression for repeated measures with general estimating equations, modeling the likelihood of a cocaine-positive week over time in treatment, we found the diagnostic group to interact with the baseline level of cocaine use and time. Among cocaine-dependent patients who achieved abstinence at baseline, those with MDD and those with ADHD had better outcome over time as compared with patients with CD alone. However, among patients with cocaine-positive urine specimens at baseline, those with MDD and those with ADHD were associated with poor outcome as compared with patients with CD alone. The findings suggest that diagnosis and treatment of co-occurring disorders such as depression and ADHD may be important components of treatment planning for CD and that the baseline level of cocaine use should be included as a covariate in studies evaluating the impact of such treatment.