Treat Cocaine Use Research Articles

Serotonin 5-HT2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder.

Cocaine exhibits prominent abuse liability, and chronic abuse can result in cocaine use disorder with significant morbidity. Major advances have been made in delineating neurobiological mechanisms of cocaine abuse; however, effective medications to treat cocaine use disorder remain to be discovered. The present review will focus on the role of serotonin (5-HT; 5-hydroxytryptamine) neurotransmission in the neuropharmacology of cocaine and related abused stimulants. Extensive research suggests that the primary contribution of 5-HT to cocaine addiction is a consequence of interactions with dopamine (DA) neurotransmission. The literature on the neurobiological and behavioral effects of cocaine is well developed, so the focus of the review will be on cocaine with inferences made about other monoamine uptake inhibitors and releasers based on mechanistic considerations. 5-HT receptors are widely expressed throughout the brain, and several different 5-HT receptor subtypes have been implicated in mediating the effects of endogenous 5-HT on DA. However, the 5-HT2A and 5-HT2C receptors in particular have been implicated as likely candidates for mediating the influence of 5-HT in cocaine abuse as well as to traits (e.g., impulsivity) that contribute to the development of cocaine use disorder and relapse in humans. Lastly, new approaches are proposed to guide targeted development of serotonergic ligands for the treatment of cocaine use disorder.

Plasma profile of pro-inflammatory cytokines and chemokines in cocaine users under outpatient treatment: influence of cocaine symptom severity and psychiatric co-morbidity.

The treatment for cocaine use constitutes a clinical challenge because of the lack of appropriate therapies and the high rate of relapse. Recent evidence indicates that the immune system might be involved in the pathogenesis of cocaine addiction and its co-morbid psychiatric disorders. This work examined the plasma pro-inflammatory cytokine and chemokine profile in abstinent cocaine users (n = 82) who sought outpatient cocaine treatment and age/sex/body mass-matched controls (n = 65). Participants were assessed with the diagnostic interview Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Tumor necrosis factor-alpha, chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 and chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) were decreased in cocaine users, although all cytokines were identified as predictors of a lifetime pathological use of cocaine. Interleukin-1 beta (IL-1β), chemokine (C-X3-C motif) ligand 1 (CX3CL1)/fractalkine and CXCL12/SDF-1 positively correlated with the cocaine symptom severity when using the DSM-IV-TR criteria for cocaine abuse/dependence. These cytokines allowed the categorization of the outpatients into subgroups according to severity, identifying a subgroup of severe cocaine users (9-11 criteria) with increased prevalence of co-morbid psychiatric disorders [mood (54%), anxiety (32%), psychotic (30%) and personality (60%) disorders]. IL-1β was observed to be increased in users with such psychiatric disorders relative to those users with no diagnosis. In addition to these clinical data, studies in mice demonstrated that plasma IL-1β, CX3CL1 and CXCL12 were also affected after acute and chronic cocaine administration, providing a preclinical model for further research. In conclusion, cocaine exposure modifies the circulating levels of pro-inflammatory mediators. Plasma cytokine/chemokine monitoring could improve the stratification of cocaine consumers seeking treatment and thus facilitate the application of appropriate interventions, including management of heightened risk of psychiatric co-morbidity. Further research is necessary to elucidate the role of the immune system in the etiology of cocaine addiction.

Comorbilidad psicopatológica en consumidores de cocaína en tratamiento ambulatorio

Cocaine addiction is a growing health problem and among its complications highlights the high prevalence of mental disorders co-occurring with abuse and dependence. This psychopathological comorbidity varies according to the time of consumption and the age of the patient. Early detection of psychopathological disorders associated with drug consumption is necessary to optimize health care and to improve the prognosis. The main aim of the present study was to estimate the prevalence and characteristics of psychopathological comorbidity in a population of subjects seeking outpatient treatment for cocaine use. We recruited 110 subjects using cocaine by nasal insufflations evaluated with the PRISM (Psychiatric Research Interview for Substance and Mental Disorders), a semi-structured diagnostic interview that differentiates primary mental disorders from those induced by the drug. This population presented 86.4% male and had a mean age of 36.5. They displayed a pathological use of cocaine of 7 years and the presence of psychopathology was associated with a higher number of DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders- IV-TR) criteria for substance dependence. The lifetime prevalence of some psychopathological comorbidity was 61.8%, highlighting mood disorders (34.5%), followed by anxiety disorders (22.7%) and psychotic disorders (15.5%). About 20% showed antisocial personality disorder and 21% borderline personality disorder. From among mood and psychotic disorders, the induced disorders were more frequent, while the primary disorders were more prevalent in anxiety.

Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine.

Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate; follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine; cocaine-dependent subjects were sensitive only to 300 mg caffeine. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS ‘elated’ scales; follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3–4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. In conjunction with previous preclinical and human studies, the data suggest that adenosine modulating drugs may have value in the treatment of stimulant use disorders.

Atomoxetine does not alter cocaine use in cocaine dependent individuals: A double blind randomized trial

BackgroundCocaine abuse continues to be a significant public health problem associated with morbidity and mortality. To date, no pharmacotherapeutic approach has proven effective for treating cocaine use disorders. Preclinical and clinical evidence suggests that noradrenergic activity may play a role in mediating some effects of cocaine and may be a rational target for treatment. MethodsThis double blind, placebo-controlled randomized, parallel group, 12-week outpatient clinical trial enrolled cocaine dependent individuals seeking treatment to examine the potential efficacy of the selective norepinephrine reuptake inhibitor, atomoxetine (80mg/day; p.o.; n=25), compared to placebo (n=25). Subjects were initially stratified on cocaine use (<15 days or ≥15 days of the last 30), age and race using urn randomization. Attendance, medication adherence and study compliance were reinforced with contingency management, and weekly counseling was offered. An array of measures (vital signs, laboratory chemistries, cognitive and psychomotor tests, cocaine craving and urine samples for drug testing) was collected throughout the study and at follow-up. ResultsSurvival analysis revealed no differences in study retention between the two groups, with approximately 56% of subjects completing the 12-week study (Cox analysis χ2=.72; p=.40; Hazard Ratio 1.48 [95% CI 0.62–3.39]). GEE analysis of the proportion of urine samples positive for benzoylecgonine, a cocaine metabolite, revealed no differences between the atomoxetine and placebo groups (χ2=0.2, p=.66; OR=0.89 [95% CI 0.41–1.74]). Atomoxetine was generally well tolerated in this population. ConclusionsThese data provide no support for the utility of atomoxetine in the treatment of cocaine dependence.

The Role of Psychosocial Characteristics in Criminal Convictions Among Cocaine and Gambling Clients in Treatment

This study assessed the relative importance of problem gambling, cocaine use and selected psychosocial characteristics in predicting criminal convictions. A self-administered questionnaire was completed by clients when admitted to a treatment program for a primary problem with cocaine (n = 300), gambling (n = 199), or tobacco (n = 249). The questionnaire included questions on various psychosocial characteristics and criminal conviction(s) in the past 3 years. Those in treatment for cocaine use or gambling had higher rates of criminal conviction (21.8 % and 11.6 %, respectively) than those in treatment for tobacco (1.6 %). In a multivariate analysis, being in treatment for cocaine or gambling, compared to those in treatment for tobacco, was significantly associated with having had a criminal conviction; while having high levels of social support and being employed full-time were protective factors against criminal conviction. Due to the cross-sectional nature of the study causation cannot be inferred.

Contingency management is efficacious and improves outcomes in cocaine patients with pretreatment marijuana use

Background Marijuana use is common in patients seeking treatment for cocaine use. Nevertheless, few studies have examined effects of marijuana use on treatment outcomes in general, and even fewer with respect to contingency management (CM) treatment, which has been criticized for potentially increasing non-reinforced drug use. Methods Data from three randomized clinical trials of CM versus standard treatment (ST) in cocaine-abusing patients were examined ( Petry et al., 2004, 2005a, 2006a; N = 393) to assess effects of pretreatment marijuana use on outcomes. Patients were divided into two groups: (1) no self-reported marijuana use (No Pre-M; n = 315) and (2) any self-reported marijuana use (Pre-M; n = 78) in the 30 days pretreatment. Results CM was especially efficacious in enhancing retention in Pre-M patients such that retention nearly doubled among Pre-M patients assigned to CM versus those assigned to ST. In contrast, CM exerted only modest benefits on retention in No Pre-M patients. Pretreatment marijuana use was not related to during-treatment abstinence from cocaine, opioids, and alcohol, or abstinence at a Month 9 follow-up. However, CM treatment and longest duration of abstinence achieved during treatment were significant predictors of Month 9 abstinence. Pre-M patients also evidenced more improvements in drug problems over time when randomized to CM. Conclusions CM was especially efficacious in facilitating retention and improving severity of drug-related problems in those who used marijuana in the month before initiating treatment.

Contingency Management for the Treatment of Methamphetamine Use Disorders

Theory and some preliminary evidence suggest that contingency management may be an effective treatment strategy or adjunct to psychosocial treatment for methamphetamine use disorders. An experimentally rigorous investigation on the topic was provided by a large multisite trial conducted under the auspices of the Clinical Trials Network of the National Institute on Drug Abuse. The authors report data on 113 participants who were diagnosed with methamphetamine abuse or dependence. They were randomly assigned to receive 12 weeks of either treatment as usual or treatment as usual plus contingency management. Urine samples were tested for illicit drugs, and breath samples were tested for alcohol. The reinforcers for drug-negative samples were plastic chips, some of which could be exchanged for prizes. The number of plastic chips drawn increased with each week of negative samples but was reset to one after a missed or positive sample. The participants in both groups remained in treatment for equivalent times, but those receiving contingency management in addition to usual treatment submitted significantly more negative samples, and they were abstinent for a longer period of time (5 versus 3 weeks). These results suggest that contingency management has promise as a component in treatment strategies for methamphetamine use disorder.

A Combined Cognitive and Behavioral Intervention for Cocaine-Using Methadone Clients

Treating cocaine use by opiate-dependent clients in methadone programs is a well-documented challenge. Both behavioral (contingency management) and cognitive (relapse prevention) interventions have shown promise in helping engage these clients in treatment. In this study, the effectiveness of combining contingency management with a cocaine-specific relapse prevention counseling module was examined. Sixty-one cocaine-using methadone clients were randomly assigned to one of four treatment conditions to participate in the eight-week intervention and eight-week follow-up period. Using analysis of variance (ANOVA), differences in cocaine use and treatment retention were examined. Contingency management was significantly related to reductions in cocaine use and the counseling module was positively related to six-month retention rates. Both interventions were associated with positive treatment response but the effects were reflected in different behavioral outcomes.

Cost effectiveness of disulfiram: Treating cocaine use in methadone-maintained patients

Converging evidence suggests that disulfiram is a promising treatment for cocaine dependence. We study the cost-effectiveness of providing disulfiram to methadone-maintained opioid addicts in a randomized clinical trial setting. Our economic evaluation is based on a double blind clinical trial in which 67 cocaine-dependent methadone-maintained opioid-dependent subjects were randomized to get the additional treatment of disulfiram or placebo in a 12-week trial. Outcome measures used are the number of days of cocaine use and grams of cocaine per week. Cost measures used are the cost of providing standard methadone treatment and the incremental cost of adding disulfiram to the standard treatment. Cost measures of standard and disulfiram-enhanced treatment were collected retrospectively from the provider. Results from this cost-effectiveness analysis imply that, even though disulfiram increases slightly the cost of methadone treatment, its increase in effectiveness may be important enough to warrant its addition for treating cocaine dependence in methadone-maintained opiate addicts.

Longitudinal Treatment Effects Among Cocaine Users: A Growth Curve Modeling Approach

This study examined longitudinal treatment effects among cocaine users. The study examined a sample of 371 cocaine users screened from arrestees in jails and from patients in sexually transmitted disease clinics and emergency rooms—all in Los Angeles County during 1992–1994. Of the 371 subjects, 121 had never been in treatment and 250 reported a history of participation in drug user treatment (145 subjects' first treatment was for cocaine use and 105 were in treatment for a drug other than cocaine). Data were collected during face-to-face interviews using a natural history interview instrument. We applied a series of growth curve models to investigate treatment effects on cocaine use. For those who had been in treatment for cocaine use, use of cocaine decreased from approximately 70% before treatment to 12% after treatment entry, while no such changes were observed among those who had never been in treatment or those in treatment for other drugs. Relative to nontreated users, cocaine-treated participants showed a greater likelihood of pretreatment use for both initial status (OR = 3.58) and growth rate (OR = 1.05). After treatment entry, cocaine-treated participants as compared to nontreated participants had a lower likelihood of use (OR = 0.27), although their cocaine use after the initial status increased at a greater rate (OR = 1.03). Treated users were five times less likely to use when they were in treatment than when they were out of treatment. Longer treatment retention was related to initially reduced use but not to later rates of change in cocaine use. The study findings support that treatment for cocaine use is effective in reducing cocaine use. Longitudinal models provide opportunities to demonstrate the dynamic relationships between treatment and outcome.

Epidemic crack cocaine use linked with epidemics of genital ulcer disease and heterosexual HIV infection in the Bahamas: evidence of impact of prevention and control measures.

Epidemic freebase/crack cocaine use began in the Bahamas in 1982, closely followed by epidemics of genital ulcer disease (GUD) and HIV infection. Numbers of new clients receiving ambulatory treatment for cocaine use in Nassau peaked in 1984. To assess interrelations among epidemics of crack use, GUD, and HIV infection. The study was designed for review and comparison of temporal trends in ambulatory and inpatient treatment of cocaine users and in numbers of cases of sexually transmitted disease (STD) and HIV infection in the Bahamas. A retrospective case-control study of cocaine use and STDs was performed at the Comprehensive Dermatovenereology Clinic in Nassau. Ambulatory visits and inpatient admissions for cocaine use peaked in 1984 and 1987, respectively. GUD cases increased 12-fold in the Bahamas from 1983 to the period of 1985-1987 and then declined. At the Comprehensive Dermatovenereology Clinic, gonorrhea cases outnumbered bacterial GUD cases approximately 10:1 in 1982 and 1983, but the latter increased to outnumber gonorrhea cases in 1985 and 1987-1988. Annual HIV seroprevalences at new-problem visits rose from less than 0.3% in 1986 to 12.9% by 1994 and then leveled off. Cocaine use among patients seen with STD from 1985 through 1990 was significantly associated with GUD (odds ratio [OR], 3.3; 95% CI, 2.1-5.1), secondary syphilis (OR 5.5; 95% CI, 2.4-12.6), and HIV infection (OR, 8.1; 95% CI, 4.3-15.2). In temporally linked successive epidemics of cocaine use, GUD, and HIV infection, case-control analyses confirmed the association of cocaine use with GUD and with HIV infection. Declining GUD and HIV seroprevalence stabilization followed declines in cocaine use and implementation of syndromic management of GUD, as well as intensified partner-notification efforts.

Fluoxetine treatment of cocaine-dependent patients with major depressive disorder

Sixty-eight male and female individuals with both DSM-IV diagnoses of cocaine dependence and major depressive disorder were randomly assigned to one of two medication conditions (placebo vs. 40 mg per day) as part of a double-blind, placebo-controlled clinical efficacy trial of fluoxetine for the treatment of this dual diagnosis. During the 12-week outpatient treatment phase all participants also received individual cognitive-behavioral psychotherapy targeting both cocaine use and depression. Depressive symptoms remitted as a function of time in treatment, with no significant medication effects found. Fewer cocaine positive urines were found during the first 6 weeks of treatment in the placebo group compared with the 40-mg group. Cocaine use and depressive symptoms during treatment were significantly correlated. The findings fail to support the role of fluoxetine for treatment of cocaine use and depression in dually-diagnosed patients.

The Autonomy of Mood Disorders Among Cocaine-Using Methadone Patients

This study uses an algorithm to determine whether patients dually diagnosed with a mood disorder and cocaine dependence have either (a) an autonomous mood disorder (onset of mood disorder prior to substance use disorder (SUD) or mood disorder symptoms persist during periods of abstinence or (b) a nonautonomous mood disorder (onset of SUD preceded mood disorder and mood disorder symptoms remit during periods of abstinence). The relationship among autonomy, patient characteristics, and treatment completion is examined. The sample included 67 methadone patients with a mood disorder (87% major depression, 13% bipolar) who were enrolling in a 6-month psychosocial treatment for cocaine use. Of these subjects, 27% were rated as having an autonomous mood disorder and 73% a nonautonomous mood disorder. Mean age was 37 years; 55% were female and 82% were Hispanic or African-American. All subjects had been stabilized on methadone (mean = 70 mg). During the 30 days prior to study intake, subjects with an autonomous mood disorder, compared to subjects with a nonautonomous mood disorder, reported fewer days using cocaine (12.5 versus 21.1) and fewer days drinking four or more drinks of alcohol (1.1 versus 6.1). Treatment completion was associated with less cocaine use, autonomy, and African-American ethnicity. However, when these variables were controlled using logistic regression, only autonomous mood disorder and ethnicity predicted treatment completion. These results suggest that autonomy may be a useful construct to measure, and that subjects with nonautonomous mood disorders may need special efforts to ensure treatment retention.

Responding for Rewarding Brain Stimulation: Cocaine and Isradipine Plus Naltrexone

Rats, fixed with chronically indwelling electrodes for electrical intracranial stimulation (ICS) of the lateral hypothalamus, were taught to press a bar for ICS. Once pressing rates became stable, during daily 20-min sessions, rats were given cocaine (5 or 20 mg/kg) before the sessions. When given daily, cocaine consistently enhanced rates of pressing. When a combination of small doses of isradipine (e.g., 1 mg/kg) and naltrexone (3 mg/kg) were given before cocaine administration, the combination blocked cocaine’s enhancement of pressing for ICS. The combination, however, neither reduced rates of pressing below those observed under placebos (i.e., baseline conditions) nor reduced rates when no cocaine was given. Naltrexone and isradipine (in the dose used in the combination) by themselves did not block cocaine’s effects. This profile of effects indicates that a combination of isradipine and naltrexone is apt to be useful in treating cocaine use disorders.

A Combination of Isradipine and Naltrexone Blocks Cocaine’s Enhancement of a Cocaine Place Preference

Rats were conditioned by pairing cocaine with one side of an alley and placebo with the other. After conditioning, compared to Baseline and a placebo-control group, rats spent more time in the place of cocaine experience. Subsequently, there were further tests except now cocaine was given just before the test session in addition to one of two other kinds of injections. One of these additional injections was a placebo and the other was a combination of a small dose of isradipine (1 mg/kg) and a dose of naltrexone (3 mg/kg) (ISR+NTX). Measures of gross activity (movement from one side of the alley to the other) were taken during testing. ISR+NTX blocked cocaine’s ability to sustain a place preference. ISR+NTX also blocked sensitization of cocaine’s ability to enhance locomotor activity. This blockade of cocaine’s usual effects indicates that ISR+NTX may have a role in treating cocaine use disorders.

Relationship between Self-Efficacy Perceptions and In-treatment Drug Use among Regular Cocaine Users

The perceived ability to engage in situation-specific behaviors (self-efficacy) to overcome nicotine dependence and alcohol abuse has been shown to correlate significandy with and be predictive of the actual ability to engage in such behaviors. Self-efficacy is also related to subsequent behavior change during treatment and maintenance of this change after treatment termination. In this study, part of a national outcome study, the relationship between self-efficacy and drug use was investigated in a subsample of regular cocaine users (n = 294) who completed at least three months of treatment in community-based outpatient treatment programs. Frequency of cocaine and other drug use was reported for the period of 1 year before treatment and at 1 month and 3 months in treatment. Self-efficacy regarding resisting drug use was measured at 1 and 3 months in treatment. Self-efficacy at 1 month was correlated with cocaine use at 1 month and self-efficacy contributed to the prediction of self-reported drug use at 1 month over and above pretreatment and demographic variables. Similarly, self-efficacy at 3 months was correlated with cocaine use at 3 months and contributed to the prediction of self-reported drug use at 3 months. These outcomes were obtained even though over 75% of subjects reported no drug use during treatment. The results supported previous findings suggesting that increased self-efficacy regarding resisting drug use is associated with lower rates of drug use during treatment, and that self-efficacy enhancement may be an important intervention in the treatment of cocaine use.

Lifestyle differences between young adult cocaine users and their nonuser peers.

Health-related behaviors were examined in a group of twenty-five young adults who regularly used cocaine and in a matched sample of twenty-five nonusing young adults. We hypothesized that cocaine users would have a less healthy lifestyle as indicated by behavioral scales or items on three health domains: Nonillicit Drugs, Health Orientation, and Health Behaviors. Cocaine users consumed more cups of coffee per day, more alcoholic beverages per week, and ate fewer complete/balanced meals per day than non-users. Cocaine users also reported fewer relaxing or stress-reducing activities and less daily planning and organization. A within-groups analysis of the cocaine users revealed that the heavier users perceived themselves as less healthy relative to their peers and ate fewer complete/balanced meals. These results suggest that cocaine use is a behavior embedded within a complex of interrelated unhealthy behaviors that constitute an unhealthy lifestyle. By implication, cocaine use is associated with a greater lifestyle imbalance involving polydrug use at the expense of nutrition and effective self-management. These results suggest that clinical interventions for prevention and treatment of cocaine use should promote specific healthy lifestyle changes in addition to the current practice of promoting a cessation of drug use.

Factors which differentiate cocaine users in treatment from nontreatment users.

This study compares a sample of cocaine users in drug treatment programs to a sample of cocaine users not in treatment. These samples were compared on: (1) level of cocaine use, (2) consequences of user, (3) employment, (4) social support system, and (5) criminal behavior. These attributes were related to being in treatment. Among intermediate-level cocaine users, friendship patterns, employment, and criminal history were associated with treatment status. The implications for the treatment of cocaine use are addressed.