Cocaine-dependent Patients Research Articles

A placebo-controlled trial of memantine for cocaine dependence with high-value voucher incentives during a pre-randomization lead-in period

Preclinical findings suggest that the inhibition of NMDA glutamatergic neurotransmission may have beneficial effects in the treatment of cocaine dependence. We hypothesized that memantine, a low potency, uncompetitive NMDA receptor antagonist, would be safe and effective in the treatment of cocaine dependence, particularly in preventing relapse to cocaine use in abstinent individuals. Cocaine dependent patients ( N = 112) were enrolled. The trial began with a 2-week placebo lead-in period during which patients received high-value voucher contingency management to induce abstinence. Participants were then randomized to receive either memantine 20 mg bid ( N = 39) or placebo ( N = 42) for 12-weeks in combination with individual relapse-prevention therapy. The randomization was stratified by abstinence status during the lead-in period. The primary outcome was the weekly proportion of days of cocaine use. There were no significant differences in cocaine use outcome between the groups treated with memantine versus placebo. Thus, the efficacy of memantine 40 mg/d for the treatment of cocaine dependence was not supported. Urine-confirmed abstinence during the lead-in period was achieved by 44% of participants, and was a strong predictor of subsequent cocaine abstinence during the trial. This suggests that this clinical trial design, an intensive behavioral intervention during a lead-in period, resolves cocaine dependent patients into two subgroups, one that rapidly achieves sustained abstinence and may not need a medication, and another that displays persistent cocaine use and would most likely benefit from a medication to help induce abstinence. Targeting the latter subgroup may advance medication development efforts.

White Matter Integrity is Associated with Treatment Outcome Measures in Cocaine Dependence

Cocaine dependence is associated with white matter impairments that may compromise cognitive function and hence drug users' abilities to engage in and benefit from treatment. The main aim of this study was to assess whether white matter integrity correlates with treatment outcome measures in cocaine dependence. Diffusion tensor imaging (DTI) was used to assess the white matter (WM) of 16 treatment-seeking cocaine-dependent patients before 8 weeks of therapy. The measures for treatment outcome were longest self-reported duration of continuous cocaine abstinence, percent of urine screens negative for cocaine, and duration (weeks) of treatment retention. Correlations between treatment outcome measures and DTI parameters (fractional anisotropy (FA), longitudinal eigenvalue (lambda(1)), perpendicular eigenvalue (lambda(T)), and mean diffusivity (MD)) were analyzed. Longest self-reported abstinence from cocaine and percent of cocaine-negative urine samples during treatment positively correlated with FA values and negatively correlated with lambda(1), lambda(T), and MD values across extensive brain regions including the corpus callosum, frontal, parietal, temporal, and occipital lobes, and cerebellum. The findings of an association between better WM integrity at treatment onset and longer abstinence suggest that strategies for improving WM integrity warrant consideration in developing new interventions for cocaine dependence.

Normalizing Effects of Modafinil on Cocaine-Induced Sleep Abnormalities

Normalizing Effects of Modafinil on Cocaine-Induced Sleep Abnormalities

Increased error-related thalamic activity during early compared to late cocaine abstinence

Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task ( Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE > SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control.

Randomized trial of continuing care enhancements for cocaine-dependent patients following initial engagement.

The effects of cognitive-behavioral relapse prevention (RP), contingency management (CM), and their combination (CM + RP) were evaluated in a randomized trial with 100 cocaine-dependent patients (58% female, 89% African American) who were engaged in treatment for at least 2 weeks and had an average of 44 days of abstinence at baseline. The participants were from intensive outpatient programs, which provide 10 hr per week of group counseling. The CM protocol provided gift certificates (maximum value $1,150; mean received = $740) for cocaine-free urines over 12 weeks on an escalating reinforcement schedule, and weekly individual RP sessions were offered for up to 20 weeks. Average number of RP sessions attended was 3 in RP and 13 in CM + RP. Generalizing estimation equation analyses over 18 months postrandomization showed significant effects for CM (but not RP) on urine toxicology and self-reported cocaine use (p = .05), with no significant CM x RP interactions. Secondary analyses indicated CM + RP produced better cocaine urine toxicology outcomes at 6 months than treatment as usual, odds ratio [OR] = 3.96 (1.33, 11.80), p < .01, and RP, OR = 4.89 (1.51, 15.86), p < .01, and produced better cocaine urine toxicology outcomes at 9 months than treatment as usual, OR = 4.21 (1.37, 12.88), p < .01, and RP, OR = 4.24 (1.32, 13.65), p < .01. Trends also favored CM + RP over CM at 6 months, OR = 2.93 (0.94, 9.07), p = .06, and 9 months, OR = 2.93 (0.94, 9.10), p = .06. Differences between the conditions were not significant after 9 months. These results suggest CM can improve outcomes in cocaine-dependent patients in intensive outpatient programs who have achieved initial engagement, particularly when it is combined with RP.

PW01-242 - Risk factors for cocaine-induced psychosis in cocaine dependent patients

IntroductionCocaine consumption can induce transient psychotic symptoms, expressed as paranoia or hallucinations. Cocaine induced psychosis (CIP) is common but not developed in all cases.ObjectivesTo describe the Risk Factors for developing cocaine-induced psychosis in cocaine dependent patients, according DSM-IV-TR criteria.MethodsThis is the first European study about the relationship of CIP with consumption pattern variables and personality disorders, we evaluated 220 cocaine dependents over 18 years, 80'5% males, mean age 33.9 years (SD = 7.6). Patients were recluted from an outpatient clinic department and subsequently systematically evaluated using SCID I and SCID II interviews for comorbidity disorders, and a clinical-based systematic psychotic symptoms form.ResultsA high proportion of cocaine dependent patients reported psychotic symptoms (51.8%) under influence of cocaine. The most frequent reported psychotic symptoms were paranoid beliefs and suspiciousness (42.4%). After a logistic regression analysis we found that a model consisted of high cocaine consumption (mean of 12.01 grams per week), cannabis dependence history and to use intranasal or smoked rout of administration had a sensitivity of 63.2% and a specificity of 70.2%.ConclusionWe conclude that is relevant to evaluate CIP in patients consuming high amounts of cocaine, with cannabis dependence history and who do not use intranasal rout. It could be useful for preventing consequences or risks of psychotic states for themselves or others.

PW01-243 - The apomorphine test as a biological marker for relapse in cocaine dependent-patients

IntroductionUntil now, no reliable biological markers of risk and relapse in substance-dependent patients have been identified. The yawn-inducing test with apomorphine has been proposed as a marker of the functional status of the dopaminergic system and therefore a predictor of suffering an addiction or predisposition to relapse.ObjectivesStudying the safety and efficacy of apomorphine test as a predictor of relapse in intranasal cocaine dependent, diagnosed according to DSM-IV-TR.MethodsWe performed the test of apomorphine at the beginning (day 1) and end (day 11/12) of a detoxification program in 33 patients (29 men). The majority of patients relapsed after 22 weeks of follow up (87% relapse). The average yawns in the sample were 10.9 ± 9.3 in the initial test (Apo 1) and 10.2 ± 10.2 in the final test (Apo 2). The 42% of patients relapsed early (before 4 weeks) and 45% late (afther 4 weeks). 58% of the sample (N = 19), which did not fall belatedly filled an average of 8.0 yawns in Apo1 and 8.1 on Apo2 and 42% who did so early (N = 14), 14,8 in Apo1 and 14.6 in Apo2. Therefore there are an increased number of yawns in patients with early relapse. No important side effects were reported.ConclusionsPatients with early relapse have a higher number of yawns that those falling late or abstainers The apomorphine test is a safe test and it is a readily applicable tool in clinical practice and may be a biological marker of risk.

P03-257 - Psychotic symptoms in cocaine injecting drug users, report of healthcare professionals working in a medically supervised injection clinic (MSICS)

ObjectivesDescribe the prevalence and characteristics of psychotic symptoms in the context of cocaine injection use in a harm reduction program.To find associations between intravenous cocaine use and other drug use in cocaine dependent patients suffering from cocaine induced psychosis (CIP). Cannabis was found to be a risk factor for developing CIP in non-intravenous cocaine dependence.MethodsDuring a period of 6 months professionals from our Outpatient Drug Clinic completed a confidential questionnaire to describe the adverse clinical effects following cocaine injection. It included age, gender, ethnic group, daily consumption rate and other drugs used in the last 30 days.ResultsSurvey was achieved with a sample of 75 Caucasians patients, 69 men and 6 women with an average age of 32 years old. Seventeen percent (13/75) had psychotic symptoms, of which 84% (11/13) had hallucinations (visuals 4/11, auditive 7/11 and kinaesthetic 2/11), 15% (2/13) illusions.Eighteen percent (14/75) had stereotypy movements and 3% (2/75) had aggressive behaviour. Drugs used by CIP patients, the previous 30 days were: 61% (8/13) cannabis, 31% (4/13) opiates and 15% (2/13) alcohol.ConclusionsIntravenous cocaine use produced acute psychotic symptoms in 17% of our patients, of which 61% used cannabis. Despite the ethical and practical implications of this type of study, it is necessary to do more observational studies with bigger surveys to conclude these results with statistically significance.

Self-reports of interoceptive responses during stress and drug cue-related experiences in cocaine- and alcohol-dependent individuals.

Cocaine dependence is associated with neuroadaptations in stress and reward pathways that could alter stress and drug-related experiences and associated interoceptive sensations and result in enhanced craving states. Subjective interoceptive emotional and physiological responses experienced in stressful and drug cue situations were examined in abstinent cocaine-dependent individuals. Fifty-six treatment engaged cocaine-dependent patients with comorbid alcohol abuse or dependence were interviewed to identify personal stressful, drug cue, and neutral situations using a scene construction questionnaire (SCQ) that includes an emotional and physiological response checklist. Using this checklist, subjects identified emotional and bodily sensations that they recently experienced in the stress- and drug-related scenarios. Kappa coefficients indicated fair to moderate but significant degree of concordance in heart (p < .01), perspiration (p < .05), stomach (p < .05), and blood flow (p < .01) sensations for both stress and drug cue scenarios, while the McNemar change test indicated differential endorsement of interoceptive responses in stress and drug cue situations for breathing (p < .05), stomach (p < .05), tension (p < .05), and chest (p < .05) sensations, and for sad (p < .01), anger (p < .01), and excitement (p < .01) responses. Increased heartbeat and tension, tears, and anger urges were most commonly endorsed in the stress scenarios (between 50% and 79%), whereas butterflies in stomach, increased heartbeat and tension, jittery, restless, and warm excitement (53%-73%) were the most frequently endorsed sensations in the drug cue-related experiences. These self-reported sensations comprise both general arousal and specific interoceptive responses pertaining to stress or drug cue-related experiences in cocaine dependence, with potential value in guiding treatments targeting craving reduction.

Comparison of completers and dropouts in psychological treatment for cocaine addiction

This study investigated the characteristics associated with treatment dropout in cocaine-dependent patients. A sample of 102 cocaine-addicted patients (89 male patients and 13 female patients) was assessed at entry to a therapeutic programme in order to collect information on socio-demographic, psychopathological (assessed by SCL-90-R), personality (assessed by MCMI-II), legal and consumption variables (assessed by EuropAsi). The rate of patients who dropped out of the intervention programme was 30.4% (N = 31) of the sample. Dropouts and completers were compared on all studied variables. According to the results obtained, dropouts showed a significantly higher score on the EuropAsi variables related to alcohol consumption, family problems and need for psychological treatment, as well as on the histrionic and antisocial scales of the MCMI-II. Moreover, all patients with histrionic personality disorder dropped out of the treatment. On the other hand, completers showed a significantly higher score on the compulsive scale of the MCMI-II. The implications of these results for further research and clinical practice are commented upon.

Cocaine-Specific Antibodies Blunt the Subjective Effects of Smoked Cocaine in Humans

Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine (TA-CD) produces selective anticocaine antibodies, yet the impact of these antibodies on cocaine's direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving, and cardiovascular effects. Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week for 13 weeks inpatient where the effects of cocaine (0 mg, 25 mg, 50 mg) were determined before vaccination and at weekly intervals thereafter. Two doses of TA-CD (82 microg, n = 4; 360 microg, n = 6) were administered at weeks 1, 3, 5, and 9. Peak plasma antibody levels, which were highly variable, significantly predicted cocaine's effects. Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (55%-81%) reduction in ratings of good drug effect and cocaine quality, while those in the lower half showed only a nonsignificant attenuation (6%-26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer (p < .12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia. The TA-CD vaccine substantially decreased smoked cocaine's intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine dependence.

Baseline Neurocognitive Profiles Differentiate Abstainers and Non-Abstainers in a Cocaine Clinical Trial

ABSTRACT Previous studies have shown that cocaine users have higher levels of impulsivity and impaired decision making; however, few have examined these factors as predictors of treatment success. We obtained baseline neurocognitive measures from 75 cocaine-dependent individuals participating in a 12-week clinical trial targeting impulsivity with behavioral therapies and pharmacotherapy. Participants treated with citalopram had higher cocaine abstinence rates compared to placebo-treated participants. The aim of this secondary analysis study was to determine whether profiles of performance on neurocognitive measures administered at baseline discriminated among patients who achieved abstinence and those who did not. Participants completed the Immediate and Delayed Memory Task, Barratt Impulsiveness Scale–11, and Iowa Gambling Task. Profile analysis results showed different patterns of performance on these baseline measures as a function of outcome. Compared with non-abstinent participants, abstinent participants had higher scores on the Barratt Impulsiveness Scale–11 Non-Planning subscale and better performance on the Iowa Gambling Task. Profile differences for the two outcome groups did not vary as a function of treatment condition. Results suggest that cocaine-dependent patients entering treatment with higher impulsivity and less impaired decision-making abilities may respond favorably to targeted behavioral interventions. Neurocognitive profiles may be useful in understanding population heterogeneity and predicting differential outcomes in subgroups of cocaine abusers.

Modafinil for the treatment of cocaine dependence

Aim Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. Methods This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200 mg, and 69 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. Results The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period ( p > 0.79). However, two secondary outcomes showed significant effects by modafinil 200 mg: the maximum number of consecutive non-use days for cocaine ( p = 0.02), and a reduction in craving ( p = 0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence ( p < 0.02). Conclusions These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

Elevated cortisol and learning and memory deficits in cocaine dependent individuals: Relationship to relapse outcomes

Cocaine dependence is characterized by stress system dysregulation, including elevated cortisol activity, emotional negativity, and behavioral disinhibition. High levels of stress and glucocorticoids are also known to affect learning, memory and executive function. Therefore, we examined the relationships between chronic cocaine use, elevated distress and learning and memory dysfunction in abstinent cocaine dependent (CD) individuals, and whether these measures were associated with cocaine relapse outcomes. Stress was assessed in 36 inpatient treatment engaged CD individuals and 36 demographically matched healthy control (HC) participants using the Perceived Stress Scale (PSS) and repeated morning salivary cortisol levels over three consecutive days. The Rey Auditory Verbal Learning Test (RAVLT) was conducted to measure verbal learning, memory, and executive function. Prospective assessment of cocaine use outcomes during 90 days following discharge from inpatient treatment was also conducted. CD patients showed higher levels of distress compared to controls in PSS scores and cortisol levels. They also demonstrated a significantly reduced learning curve, and fewer correct responses and more errors on recognition. Elevated cortisol was significantly associated with worse RAVLT performance in CD patients. Poor memory scores, but not distress measures, were significantly associated with greater cocaine use after inpatient treatment. These findings are the first to demonstrate that learning and memory deficits in CD individuals are associated with enhanced cortisol and with cocaine use outcomes after inpatient treatment. The findings are consistent with recent addiction models suggesting that chronic cocaine-related neuroadaptations affects learning and memory function, which in turn, influences drug use outcomes.

Early abstinence in cocaine pharmacotherapy trials predicts successful treatment outcomes

There is a robust relationship between early and later abstinence in smoking cessation, but that relationship has not been explored among other substances of abuse. To assess whether early abstinence during treatment, as opposed to baseline abstinence, predicted later abstinence among cocaine-dependent patients, data from two randomized double-blind controlled clinical pharmacotherapy trials were analyzed. Similar to the findings in the smoking cessation literature, results indicate that abstinence in the first 2 weeks of pharmacotherapy predicted later in-trial abstinence. This finding has implications both for treatment research and for clinical practice, suggesting that patients who do not respond early in treatment may need a more intensive intervention.

Characteristics of Cocaine Dependent Patients Who Attempt Suicide

There have been few studies examining risk factors for attempting suicide among cocaine dependent patients. Therefore, a large group of 406 abstinent cocaine dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. The results showed that 43.5% of the patients had attempted suicide. Attempters were younger; more were female; more reported childhood trauma, a family history of suicidal behavior, a history of aggression, treatment with antidepressant medication, and comorbidity with alcohol and opiate dependence. Logistic regression revealed that childhood physical abuse, childhood emotional negelect, comorbidity with alcohol dependence, and treatment with antidepressant medication were significant predictors of attempting suicide. Thus these results suggest that attempting suicide is common among cocaine dependent patients and that both distal and proximal risk factors may play a role.

Predictors of Treatment Outcome in Outpatient Cocaine and Alcohol Dependence Treatment

We examined the ability of several baseline variables to predict treatment outcome in a pharmacotherapy trial that included 164 participants who were both cocaine- and alcohol-dependent and were selected for a randomized, double-blind, placebo-controlled study. Predictor variables included results from the baseline Addiction Severity Index (ASI), initial Urine Drug Screen results, cocaine and alcohol craving and cocaine and alcohol withdrawal symptoms at the start of treatment. Successful treatment was defined as four continuous weeks of self-reported cocaine abstinence verified by urine drug screens. In respect to demographic characteristics, there were no significant differences between patients who achieved four weeks of abstinence from cocaine and those who did not. Baseline variables that most consistently predicted cocaine abstinence included initial urine drug screen (UDS) results, the initial Cocaine Selective Severity Assessment (CSSA) scores, and initial self-reported cocaine use in past 30 days, whereas cocaine craving, cocaine composite scores, alcohol craving, alcohol withdrawal symptoms, and alcohol composite scores did not. The results of this study suggest that cocaine dependence severity in general, and initial UDS results, the CSSA scores and frequency of recent cocaine use in particular, have a significant impact on treatment outcome in the treatment of cocaine-dependent patients with comorbid alcoholism. Initial UDS results and CSSA scores are very useful predictors of treatment outcome and could be used as stratifying variables in outpatient cocaine and alcohol medication trials.

Cocaine Dependence and Concurrent Marijuana Use: A Comparison of Clinical Characteristics

Background/Objectives: Marijuana is the most commonly used illicit substance, yet among the least studied in medication development research. Cocaine-dependent individuals frequently also use marijuana; however, little is known about the effect of this combined use on treatment presentation. Methods: Marijuana use was assessed in 1183 individuals seeking outpatient treatment for cocaine dependence. Based on past 30 days of use, the sample was divided into three groups: () patients reporting no recent marijuana use (n = 634); () occasional use (n = 403); () and frequent concurrent marijuana use (n = 146). Differences on baseline measures of substance use, addiction severity (ASI), psychopathology, and sociodemographic characteristics were examined as a function of level of marijuana use. Results: Frequent marijuana users were more likely to be female, Caucasian, and younger than other groups. Cocaine-dependent patients with frequent marijuana use also used more cocaine and alcohol, and reported more medical, legal, and psychiatric problems, including antisocial personality disorder. Conclusion and Scientific Significance: Cocaine-dependent patients with frequent marijuana use present for treatment with more severe impairment. Accounting for this heterogeneity among participants may improve treatment outcome.

Smoking in Pregnant Women Screened for an Opioid Agonist Medication Study Compared to Related Pregnant and Non-Pregnant Patient Samples

Background: Little is known about the prevalence and severity of smoking in pregnant opioid dependent patients. Objectives: To first characterize the prevalence and severity of smoking in pregnant patients screened for a randomized controlled trial, Maternal Opioid Treatment: Human Experimental Research (MOTHER), comparing two agonist medications; and second, to compare the MOTHER screening sample to published samples of other pregnant and/or patients with substances use disorders. Methods: Pregnant women (N = 108) screened for entry into an agonist medication comparison study were retrospectively compared on smoking variables to samples of pregnant methadone-maintained patients (N = 50), pregnant opioid or cocaine dependent patients (N = 240), non-pregnant methadone-maintained women (N = 75), and pregnant non-drug-addicted patients (N = 1,516). Results: Of screened patients, 88% (n = 95) smoked for a mean of 140 months (SD = 79.0) starting at a mean age of 14 (SD = 3.5). This rate was similar to substance use disordered patients and significantly higher compared to general pregnant patients (88% vs. 22%, p < .001). Conclusion and Scientific Significance: Aggressive efforts are needed to reduce/eliminate smoking in substance-abusing pregnant women.

Cognition, commitment language, and behavioral change among cocaine-dependent patients.

Patients' cognitive abilities and verbal expressions of commitment to behavioral change predict different aspects of substance abuse treatment outcome, but these 2 traits have never been examined conjointly. The authors therefore investigated patients' cognitive abilities and verbal expressions of commitment to behavioral change as predictors of retention and drug use outcomes in an outpatient cognitive behavioral treatment (CBT) of adult cocaine-dependent patients. A neuropsychological battery was administered at baseline. Two independent raters used recordings of CBT sessions to code commitment language strength across the temporal segments (e.g., beginning, middle, and end) of 1 session per patient. Better cognitive abilities predicted treatment retention (p < .01) but not drug use, whereas mean commitment strength across the session segments predicted reduced drug use (p = .01). Results indicate that although commitment to behavioral changes such as abstinence may occur independently of patients' cognitive abilities, engagement in the behavioral intervention process appears to depend on cognitive abilities. Future clinical studies should further investigate the relations between cognition and commitment to change and their differential contributions to treatment processes and outcome.