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Background: In rodents, cholinesterase inhibitors can cause sustained decreases in the reinforcing effects of cocaine. Nonetheless, cocaine is metabolized by butyrylcholinesterase (BuChE), raising concerns that cholinesterase inhibition could increase its peripheral concentrations, perhaps augmenting toxicity. Although donepezil is approved for use in patients and selective for inhibiting acetylcholinesterase over BuChE, no studies have reported cocaine bioavailability in human subjects receiving donepezil., Methods: Twelve cocaine-dependent veterans received three days of treatment with either oral placebo or 5 mg daily of donepezil, followed by cross-over to the opposite treatment. During both oral treatments, double-blind intravenous cocaine was administered at .0, .18, and .36 mg/kg in a laboratory setting, followed by determinations of heart rate, blood pressure, and plasma concentrations of cocaine and major metabolites., Results: Intravenous cocaine produced dose-related increases in systolic blood pressure that were most pronounced over the initial 30 minutes after treatment. Oral donepezil attenuated drug-induced elevations of systolic blood pressure following low-dose cocaine (.18 mg/kg). No significant difference in blood pressure following treatment with placebo or donepezil after high-dose cocaine (.36 mg/kg). Peak values of blood pressure and heart rate were unaffected by donepezil. Plasma concentrations of cocaine and metabolites did not differ in donepezil- and placebo-treated participants., Conclusions and Scientific Significance: We conclude that donepezil can attenuate drug-induced increases in systolic blood pressure following low-dose cocaine, but does not otherwise modify the cardiovascular effects of intravenous cocaine. Clinically significant changes in cocaine bioavailability and cardiovascular effects do not occur following this dose of donepezil. (Am J Addict 2016;25:392-399)., (© 2016 American Academy of Addiction Psychiatry.)

Background: The key objectives of this study were to examine whether HIV infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies (ARTs) to subclinical coronary artery disease (CAD) in HIV-infected persons., Methods and Results: Between June 2004 and February 2015, 1429 African American (AA) adults with/without HIV infection in Baltimore, Maryland, were enrolled in an observational study of the effects of HIV infection, exposure to ART, and cocaine use on subclinical CAD. The prevalence of subclinical coronary atherosclerosis was 30.0% in HIV-uninfected and 33.7% in HIV-infected (P=0.17). Stratified analyses revealed that compared to HIV-uninfected, HIV-infected ART naïve were at significantly lower risk for subclinical coronary atherosclerosis, whereas HIV-infected long-term ART users (≥36 months) were at significantly higher risk. Thus, an overall nonsignificant association between subclinical coronary atherosclerosis and HIV was found. Furthermore, compared to those who were ART naïve, long-term ART users (≥36 months) were at significantly higher risk for subclinical coronary atherosclerosis in chronic cocaine users, but not in those who never used cocaine. Cocaine use was independently associated with subclinical coronary atherosclerosis., Conclusions: Overall, HIV infection, per se, was not associated with subclinical coronary atherosclerosis in this population. Cocaine use was prevalent in both HIV-infected and -uninfected individuals and itself was associated with subclinical disease. In addition, cocaine significantly elevated the risk for ART-associated subclinical coronary atherosclerosis. Treating cocaine addiction must be a high priority for managing HIV disease and preventing HIV/ART-associated subclinical and clinical CAD in individuals with HIV infection., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: The presence of cocaine dependence is under-recognized by cocaine users and requires a careful standardized interview to be ascertained by clinicians., Objective: To test if past experiences of cue-induced physical symptoms of craving (nausea, vomiting, sweating, shaking, nervousness) before cocaine use could be a useful way to boost the diagnosis of cocaine dependence., Methods: A cross-sectional study of 221 cocaine users from several outpatient addiction treatment services in France, addressing the most severe period of cocaine use. DSM-IV cocaine dependence was determined with the MINI International Neuropsychiatric Interview (MINI). Physical symptoms before using cocaine were retrospectively assessed with a single item rated on a 0-5 scale., Results: The prevalence of DSM-IV cocaine dependence was 84.6%. The mean score on the physical symptoms item was 1.3 (SD 1.3). A cut-off score of ≥ 1 on this item alone resulted in a sensitivity of 62%, a specificity of 88.2%, a positive predictive value of 96.6% and a negative predictive value of 29.7% to detect DSM IV cocaine dependence in this sample. Adding this item to a model with the frequency of cocaine use significantly increased the predictive power: Nagelkerke's R(2) increased from .149 to .326 (p < .001)., Discussion and Conclusion: Recalling past experiences of cue-induced physical signs of cocaine craving is associated with a clinical diagnosis of lifetime cocaine dependence and could be a simple way to improve its detection in clinical settings., (© American Academy of Addiction Psychiatry.)

Cocaine dependence is defined by a loss of inhibitory control over drug-use behaviors, mirrored by measurable impairments in laboratory tasks of inhibitory control. The current study tested the hypothesis that deficits in multiple subprocesses of behavioral control are associated with reliable neural-processing alterations that define cocaine addiction. While undergoing functional magnetic resonance imaging (fMRI), 38 cocaine-dependent men and 27 healthy control men performed a stop-signal task of motor inhibition. An independent component analysis on fMRI time courses identified task-related neural networks attributed to motor, visual, cognitive and affective processes. The statistical associations of these components with five different stop-signal task conditions were selected for use in a linear discriminant analysis to define a classifier for cocaine addiction from a subsample of 26 cocaine-dependent men and 18 controls. Leave-one-out cross-validation accurately classified 89.5% (39/44; chance accuracy = 26/44 = 59.1%) of subjects with 84.6% (22/26) sensitivity and 94.4% (17/18) specificity. The remaining 12 cocaine-dependent and 9 control men formed an independent test sample, for which accuracy of the classifier was 81.9% (17/21; chance accuracy = 12/21 = 57.1%) with 75% (9/12) sensitivity and 88.9% (8/9) specificity. The cocaine addiction classification score was significantly correlated with a measure of impulsiveness as well as the duration of cocaine use for cocaine-dependent men. The results of this study support the ability of a pattern of multiple neural network alterations associated with inhibitory motor control to define a binary classifier for cocaine addiction., (© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.)

Objective: To describe the clinical and serologic abnormalities in 6 patients who presented with retiform purpura and extensive cutaneous necrosis after exposure to levamisole-adulterated cocaine., Methods: All patients were evaluated at San Francisco General Hospital or the University of California San Francisco Medical Center. Each underwent standard screening for substances of abuse and had urine tested for the presence of levamisole by liquid chromatography tandem mass spectrometry. Routine laboratory, autoantibody, and antiphospholipid antibody testing was performed in the hospitals' clinical or reference laboratories. Testing for atypical antineutrophil cytoplasmic antibodies (ANCAs) was performed separately using commercially available enzyme-linked immunosorbent assay kits., Results: The patients were women ages 39-50 years who presented with retiform purpura and cutaneous necrosis. Skin biopsies revealed a predominantly small-vessel thrombotic vasculopathy with varying degrees of vasculitis. Four patients were neutropenic. All tested positive for lupus anticoagulant, had IgM antibodies to cardiolipin, and tested strongly positive for ANCAs in a perinuclear pattern by immunofluorescence. Each patient had antibodies to multiple components of neutrophil granules, including neutrophil elastase, lactoferrin, cathepsin G, proteinase 3, and myeloperoxidase., Conclusion: Rheumatologists should be aware of this distinctive form of necrotic purpura, its associated autoantibodies, and its link to levamisole-adulterated cocaine., (Copyright © 2011 by the American College of Rheumatology.)

Chronic use of cocaine is associated with a variety of behavioral symptoms. The current report describes the assessment of cocaine-related behavioral symptoms (CRB) using the Scale for Assessment of Positive Symptoms of Cocaine-Induced Psychosis (SAPS-CIP). The CRB section, one of the three domains in the SAPS-CIP, consists of sub-domains, including Aggressive/Agitated Behavior, Repetitive/Stereotyped Behavior, and Unusual Social or Sexual Behavior. Severity scores are assigned according to operational criteria, and range from 0 (not present) to 5 (severe). We interviewed 261 unrelated cocaine-abusing adults using the SAPS-CIP, and 243 of them met criteria for inclusion in the study. The proportion of subjects endorsing different classes of CRBs varied across categories, with 109 of 243 (44.9%) subjects reporting aggressive and agitated behaviors, 180 subjects (74.1%) repetitive/stereotyped behaviors, and 192 (79.0%) unusual social/sexual behaviors. A substantial minority of the subjects (10.3-25.1%) reported that they experienced marked-to-severe behavioral symptoms associated with cocaine use. The proportions of subjects endorsing CRB did not differ by ethnic/racial group or by sex. Correlations among the different domains of CRB were strong, but behaviors rated in the CRB section were less well correlated with psychotic symptoms, which were rated in the hallucination and delusion sections of the instrument. A variety of CRBs are common in cocaine-dependent subjects, and many of these are highly intercorrelated. CRBs also correlate with hallucinations and delusions induced by cocaine, but to a lesser degree. Our findings suggest that there may be some common vulnerability factors that contribute to both cocaine-induced psychosis and CRBs.

In this study we present the addiction severity profile in a sample of 202 cocaine addicts, using the composite scores for each area of the EuropASI (European version of the ASI), which are compared with the severity ratings obtained through interviewers' subjective assessments. The results showed that the areas of the EuropASI which reflected the greatest severity according to the composite scores were, in the following order: employment/support, family/social situation, use of alcohol and psychiatric state. The results obtained with the composite scores show discrepancies with those obtained from the severity rating. Statistically significant differences were found in the areas of alcohol (Z = -6.205; p < 0.001), drugs (Z = -11.902; p < 0.001), family/social (Z = -6.915; p < 0.001) and psychiatric status (Z = -6.651; p < 0.001). The results call into question the reliability and validity of severity ratings obtained through interviewers' subjective assessments. For diagnosis and research, a more objective appraisal is recommended, using composite scores, since severity ratings depend totally on the interviewer's judgement, and do not appear to constitute a sound measure for estimating therapeutic change.

We investigated the presence of DSM-IV subtyping for dependence on cocaine and amphetamines (with versus without physical dependence) among outpatient stimulant users enrolled in a multisite study of the Clinical Trials Network (CTN). Three mutually exclusive groups were identified: primary cocaine users (n = 287), primary amphetamine users (n = 99), and dual users (cocaine and amphetamines; n = 29). Distinct subtypes were examined with latent class and logistic regression procedures. Cocaine users were distinct from amphetamine users in age and race/ethnicity. There were four distinct classes of primary cocaine users: non-dependence (15%), compulsive use (14%), tolerance and compulsive use (15%), and physiological dependence (tolerance, withdrawal, and compulsive use; 56%). Three distinct classes of primary amphetamine users were identified: non-dependence (11%), intermediate physiological dependence (31%), and physiological dependence (58%). Regardless of stimulants used, most female users were in the most severe or the physiological dependence group. These results lend support for subtyping dependence in the emerging DSM-V.

Aims: Cocaine is the second most-used illicit drug world-wide and its consumption is increasing significantly, especially in western Europe. Until now, the annual prevalence has been estimated indirectly by means of interviews. A recently introduced and direct nation-wide approach based on measurements of the major urinary excreted metabolite of cocaine, benzoylecgonine, in wastewater is proposed., Design: Wastewater samples from 41 wastewater treatment plants (WWTPs) in Belgium, covering approximately 3,700,000 residents, were collected. Each WWTP was sampled on Wednesdays and Sundays during two sampling campaigns in 2007-08. Samples were analysed for cocaine (COC) and its metabolites, benzoylecgonine (BE) and ecgonine methylester (EME) by a validated procedure based on liquid chromatography coupled with tandem mass spectrometry. Concentrations of BE were used to calculate cocaine consumption (g/day per 1000 inhabitants) for each WWTP region and for both sampling campaigns (g/year per 1000 inhabitants)., Findings: Weekend days showed significantly higher cocaine consumption compared with weekdays. The highest cocaine consumption was observed for WWTPs receiving wastewater from large cities, such as Antwerp, Brussels and Charleroi. Results were extrapolated for the total Belgian population and an estimation of a yearly prevalence of cocaine use was made based on various assumptions. An amount of 1.88 tonnes (t) per year [standard error (SE) 0.05 t] cocaine is consumed in Belgium, corresponding to a yearly prevalence of 0.80% (SE 0.02%) for the Belgian population aged 15-64 years. This result is in agreement with an earlier reported estimate of the Belgian prevalence of cocaine use conducted through socio-epidemiological studies (0.9% for people aged 15-64 years)., Conclusions: Wastewater analysis is a promising tool to evaluate cocaine consumption at both local and national scale. This rapid and direct estimation of the prevalence of cocaine use in Belgium corresponds with socio-epidemiological data. However, the strategy needs to be refined further to allow a more exact calculation of cocaine consumption from concentrations of BE in wastewater.

The primary objective of this study was to compare and contrast psychotic symptoms reported by cocaine- and methamphetamine-dependent individuals. Participants included 27 cocaine-dependent and 25 methamphetamine-dependent males, as well as 15 cocaine-dependent and 18 methamphetamine-dependent females. After screening, participants were excluded if they met criteria for any Axis I diagnosis other than nicotine dependence, or methamphetamine or cocaine dependence (ie, participants had to use either methamphetamine or cocaine but were excluded if they met dependence criteria for both). The participants were administered the newly developed Psychotic Symptom Assessment Scale (PSAS), which assesses psychotic symptoms. A high proportion of both cocaine- and methamphetamine-dependent men and women reported delusions of paranoia and auditory hallucinations. However, during the abstinent and intoxicated conditions, methamphetamine-dependent men and women were more likely than cocaine-dependent men and women to report psychotic symptoms. Future studies will compare psychotic symptoms reported by non-dependent recreational stimulant users to stimulant-dependent individuals.

The present study examines the diagnostic challenges of identifying ante-mortem illicit substance use in human postmortem cases. Substance use, assessed by clinical case history reviews, structured next-of-kin interviews, by general toxicology of blood, urine and/or brain, and by scalp hair testing, identified 33 cocaine, 29 cannabis, 10 phencyclidine and nine opioid cases. Case history identified 42% cocaine, 76% cannabis, 10% phencyclidine and 33% opioid cases. Next-of-kin interviews identified almost twice as many cocaine and cannabis cases as Medical Examiner (ME) case histories, and were crucial in establishing a detailed lifetime substance use history. Toxicology identified 91% cocaine, 68% cannabis, 80% phencyclidine and 100% opioid cases, with hair testing increasing detection for all drug classes. A cocaine or cannabis use history was corroborated by general toxicology with 50% and 32% sensitivity, respectively, and with 82% and 64% sensitivity by hair testing. Hair testing corroborated a positive general toxicology for cocaine and cannabis with 91% and 100% sensitivity, respectively. Case history corroborated hair toxicology with 38% sensitivity for cocaine and 79% sensitivity for cannabis, suggesting that both case history and general toxicology underestimated cocaine use. Identifying ante-mortem substance use in human postmortem cases are key considerations in case diagnosis and for characterization of disorder-specific changes in neurobiology. The sensitivity and specificity of substance use assessments increased when ME case history was supplemented with structured next-of-kin interviews to establish a detailed lifetime substance use history, while comprehensive toxicology, and hair testing in particular, increased detection of recent illicit substance use.

Introduction and Aims: There is no generally accepted clinical or research instrument available for recording the longitudinal course of a drug-using 'career'. This paper reports on an initial examination of the properties of the Lifetime Drug Use History Questionnaire (LDUH), built around monthly mapping of drug use patterns in relation to other life events., Design and Methods: Forty heroin and cocaine users completed structured interviews at two treatment sites. Twenty subjects were interviewed on two occasions separated by a 3-day interval, using either the same interviewer (n = 10) or two different interviewers (n = 10) as assessments of inter-rater and test - retest reliability., Results: Very good inter-rater agreements were observed, demonstrated by Cronbach's alpha and intraclass correlation coefficients generally higher than 0.8 and 0.7, respectively. Additionally, concordance with clinical notes was assessed for four drug use history variables, resulting in poorer rates of agreement. An exact matching with clinical records was obtained for the variable 'age of first use of heroin' in 47.2% (n = 17) of the heroin users, while a good agreement (only 1 or 2 years' difference) was found in 36.1% of cases (n = 5)., Discussion and Conclusions: The LDUH method resulted in high reliability for heroin and cocaine and suggests an effective, clinically applicable method for history-taking. The paucity and inconsistency of similar information in the clinical notes would further justify the use of a standardised method for recording drug histories.

Cocaine dependence (CD) is often accompanied by major depressive disorder (MDD). The comorbid condition (CD + MDD) is especially difficult to treat, with relapse possibly made more likely by intensified dysphoria during abstinence in the setting of MDD. We studied treatment-seeking CD + MDD volunteers, currently depressed, and a comparison CD group over three days of inpatient monitored abstinence. At admission, Beck Depression Inventory (BDI) and anxiety scores differed significantly between groups. By Day 3, BDI scores improved for both CD and CD + MDD groups. The mood response to cocaine cessation among CD + MDD individuals resembled that of CD participants, contrary to some expectations.

This study compared pretreatment addiction severity profiles of 339 abusers in three diagnostic groups: cocaine dependence only (CO), cocaine dependence with substance-induced major depression (SIMD), and cocaine dependence with independent major depression (IMD). Depressed subjects reported more severe problems than non-depressed subjects across numerous domains, regardless of diagnostic etiology. These findings support the need for specialized treatment approaches targeting depressive symptoms or life stress for cocaine-dependent patients with IMD or SIMD, though patients with IMD may require additional attention for chronic and comorbid psychiatric and medical problems.

This study examined gender differences within a sample of Canadian Aboriginal individuals admitted to an inpatient, hospital-based substance abuse detoxification program. Even though alcohol was the most frequent primary drug of detoxification for both genders, women received proportionately higher rates of cocaine or opiate detoxification diagnoses. In addition to a younger age, females reported higher rates of physical and sexual abuse. Women were also administered antidepressants, antibiotic medication protocols, and more medical evaluation tests. It appears that Canadian Aboriginal women have a diverse set of psychological and medical needs. This study demonstrates the need for detoxification programs to address the substantial rates of intravenous drug use and the associated risk of infectious disease (eg, Hepatitis C, HIV) among this treatment-seeking population.

The Addiction Severity Index (ASI) is a multi-dimensional interview used to measure the substance use, health, and social problems of those with alcohol and other drug problems, both at admission to treatment and subsequently at follow-up contacts. This article first discusses the conceptual and practical importance of the ASI's multi-dimensional approach to measuring addiction severity, as illustrated by two case presentations. The second section of the paper reviews how this measurement approach has led to some important findings regarding the prediction and measurement of addiction treatment effectiveness. The third section describes the historical and practical considerations that have changed the instrument over time, details the problems with the instrument, and describes our efforts to correct those problems with the ASI-6. Finally, some recent ASI data collected from over 8,400 patients admitted to a nationally representative sample of U.S. addiction treatment programs are presented.

The association between borderline personality disorder (BPD) and substance use disorder (SUD) was examined in a predominantly psychiatric (77.6%) sample of 232 women. BPD proved to be a significant predictor of a lifetime diagnosis of SUD across four different categories: any SUD (including alcohol); alcohol use; drug use; and heroin, cocaine, or poly-substance use. BPD continued to be a predictor of SUD even when the effects of other cluster B and all cluster C PDs were controlled statistically. Antisocial personality disorder generally yielded larger odds ratios than BPD and emerged as a partial mediator of the relation between BPD and SUD. Histrionic PD was the only other PD that showed meaningful relations with SUD.

Since 1997, substance users have received disability benefits only for impairments apart from their substance use disorders. It is hypothesized that substance users currently receiving disability benefits would be more severely compromised, medically and/or psychiatrically, than those not receiving disability. Enrolling a community sample of 330 heroin and cocaine users between January 2002 and January 2004, it was found that individuals who were not receiving disability payments had similar mental health scores, current depressive symptoms scores, and lifetime rates of major depression compared to those receiving payments, but significantly lower rates of bipolar or psychotic disorders and psychiatric hospitalization (p < .01). Physically disabled persons had lower physical function scores and were more likely to be HIV-infected or taking medications regularly (p < .001). The authors conclude that schizophrenia, bipolar disorders, and chronic physical illness, but not major depression, are qualifying substance users for disability benefits. Longitudinal studies of disability status and its effects on the lives of substance users are warranted.

Using the Addiction Severity Index and Brief Symptom Inventory, drug use and psychosocial problems are compared between 93 custodial and 125 non-custodial mothers and fathers initiating outpatient treatment for cocaine dependence. Compared to non-custodial parents, custodial parents experienced more severe current cocaine and alcohol problems, including spending more money on cocaine and alcohol, as well as using more cocaine and being intoxicated on more days. Non-custodial parents demonstrated more psychological distress, more prior history of alcohol problems, and greater current employment and legal problems than custodial parents. Suggestions are made for differential treatment plans based on these findings.

Objective: Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL., Methods: HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme-linked immunosorbent assays using purified native HNE as target antigen., Results: Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven percent of HNE ANCA-positive CIMDL sera were also PR3 ANCA-positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA-negative, as were sera obtained from healthy controls., Conclusion: Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.

The goals of the current study were to determine whether incorporating disability benefit management into combined outpatient psychiatric/addiction treatment was feasible and clinically useful for managing severely mentally ill, substance-abusing patients over time, and then if patients in this program would demonstrate the first-week-of-the-month increased substance abuse and hospitalizations shown in other studies. Forty-four patients were studied for an average of forty weeks, with little treatment or study dropout. There was no evidence in either the schizophrenic/cocaine abuser or the broader diagnostic sample of the cyclic first-of-the-month pattern of substance use and hospitalizations observed in other studies. Findings suggest that combined treatment/benefit management programs are clinically feasible and effective in stabilizing patients and keeping them in treatment.

Aim: Failure to disclose cocaine use can have a negative impact on medical care and research validity. This study was performed to identify predictors of cocaine non-disclosure among individuals who self-reported heroin use during a medical care encounter., Design: A prospective comparison of self-report of cocaine use among heroin users and hair analysis for cocaine., Setting: Four health-care clinics at an academic, inner-city hospital., Participants: Patients presenting for a health-care visit who were willing to self-report use of heroin and were not engaged in any form of drug treatment., Measurements: (1) Self-report using standardized instruments: the Drug Addiction Severity Test (DAST), the Addiction Severity Index (ASI) and quantity/frequency questions for heroin and cocaine use. (2) Biochemical evidence: analysis of hair by radioimmunoassay (RIA) for cocaine and opiate levels., Findings: Among 336 heroin users who tested positive for cocaine in hair, 34.2% did not report their recent cocaine use. The mean cocaine level for discordant individuals was significantly lower than for concordant individuals (109.6 ng/10 mg versus 470.57 ng/10 mg; P < 0.0001). Multivariate predictors of disclosure included opiate and cocaine levels in hair and the ASI drug severity subscore., Conclusions: Although self-report has been validated for treatment system patients, almost a third of the out-of-treatment heroin users in this medical clinic study failed to disclose concomitant cocaine use. The likelihood of non-disclosure was greatest for heavy users of heroin and light users of cocaine. Confirmation of self-report with biochemical analysis in the medical setting may be necessary to improve both clinical care and research validity.

We investigated whether platelet-tritiated paroxetine binding, a measure of serotonin uptake sites, and behavioral measures of impulsivity, aggression, and craving differed between cocaine-dependent subjects and controls and whether paroxetine binding was related to these behavioral measures. One hundred and five African-American cocaine-dependent outpatients and 44 African-American controls were studied. Tritiated paroxetine binding sites on platelets were assayed, and standardized assessments of impulsivity, aggression, and craving were performed. The Bmax values of paroxetine binding were significantly reduced among cocaine patients compared to controls. Cocaine patients showed significantly higher scores on certain measures of sensation seeking, impulsivity, and aggression as compared to controls. Furthermore, paroxetine binding showed a significant negative correlation with most measures of sensation seeking, impulsivity, and aggression--though not craving--among cocaine patients. Our findings indicate that densities of serotonin uptake sites may be reduced among cocaine abusers and related to impulsive-aggressive behavioral dimensions.

A continuing social problem is presented by the large number of individuals who use crack cocaine. Recent research has identified unique pyrolysis products of crack or burned cocaine as anhydroecgonine methylester (AEME) and ecgonidine (ECD) through gas chromatography/mass spectrometry (GC/MS) that allow for the detection of crack use distinct from other cocaine use. However, there have been no large-scale studies to document the presence and prevalence of these substances in sweat. A new sweat-testing appliance called a fastpatch was developed for this study. Through mild heating and a slightly larger collection pad than a standard Pharmchek( trade mark ) sweat patch, this product shows the promise of shorter required wear periods than standard sweat patches, and possibly longer time-periods of detected use. One hundred and eighty subjects wore 360 fastpatch prototypes (one per hand). However, subsequent analysis determined that only one patch per subject was needed to obtain sufficient sweat eluate for GC/MS. Cocaine use was detected in sweat of 92% of subjects through GC/MS, comparing favorably with 91% with EMIT urinalysis. Crack metabolites were detected in 54% of subjects. The predominant analyte detected was AEME. There were no significant differences in detection rates between 15-, 20- and 30-minute wear periods. All wear periods detected both cocaine use in general and crack use successfully. These results suggest that crack use as distinct from other cocaine use can be detected in sweat and that fastpatches are a promising new way to detect drugs of abuse.

Background: Recent studies suggest that a progression occurs from alcohol abuse to alcohol dependence. Although DSM-IV criteria for all substance use-related diagnoses are based largely on the alcohol dependence syndrome, progression from abuse to dependence might not generalize to other substances., Aims: This study tested whether a progression from DSM-IV abuse to dependence occurs related to the use of cannabis, cocaine and opiates., Design: Retrospective data from the DSM-IV Substance Use Disorders Work Group (n = 1226) were reanalysed using McNemar's chi2, configural frequency analyses and survival analyses. Participants were men and women who were primarily African-Americans or Caucasians., Settings: Participants were recruited from community and clinical settings. The measure was the Composite International Diagnostic Interview-Substance Abuse Module., Findings: For all substances, life-time dependence in the absence of life-time abuse was rare. Results were consistent with a progression occurring for alcohol and cannabis, but not for cocaine and opiates. Abuse and dependence occurred in the same year for 66% of the cocaine users who experienced both disorders (57% of users with any cocaine disorder) and 65% of the opiate users who experienced both disorders (46% of users with any opiate disorder). Because cocaine and opiate dependence in the absence of abuse were rare, it is possible that progressions in cocaine and opiate disorders occur more rapidly than cannabis and alcohol., Conclusions: Research is needed to clarify the mechanisms that influence progressions of substance use disorders. Potential factors leading to between-drug variation in rate of progression of disorders are discussed.

Aims: To evaluate the advantages of using a sweat patch (PharmCheck) for detecting cocaine abuse in cocaine-dependent patients participating in a clinical trial. The utility of the sweat patch was assessed from the following perspectives: the reliability and validity of quantitative sweat patch results, the possible degradation of cocaine to benzoylecgonine (BE) as a function of the length of time that a patch is worn, the completeness of the dataset yielded by thrice-weekly urine toxicology compared with thrice-weekly and weekly sweat patches, and the relative costs associated with sweat patch versus urine measures., Design: Data were collected during a 10-week out-patient clinical trial in which participants wore two sweat patches, one applied every visit and one applied weekly. Urine samples were collected thrice weekly, as were self-reports of substance use., Setting: A multi-site clinical trial conducted in Boston, Cincinnati and New York, USA., Participants: Twenty-seven participants with comorbid diagnoses of cocaine dependence and adult attention deficit disorder completed the study., Measurements: Sweat patch and urine samples were analyzed by standard methods for cocaine and cocaine metabolites., Findings: Quantitative sweat patch measures had good reliability in that the correlation between the weekly and per-visit patches was 0.96 (P < 0.0001). The concurrent validity, as judged by the correlation between quantitative urine BE levels and either weekly (0.76, P < 0.0001) or per-visit (0.73, P < 0.0001) cocaine sweat patch levels was reasonable. The correlation between the self-report of cocaine use and these same two patches, however, was lower (0.40, P < 0.05 and 0.30, P < 0.05, respectively). The results revealed no significant degradation of cocaine to BE associated with wearing the patch for a longer time. Finally, the per-visit patch provided cocaine use data on 80.5% of all study days (a total of 70), while urine toxicology and the weekly patch provided 77.4% and 76.1%, respectively., Conclusions: The present findings suggest that the PharmCheck patch might be an attractive alternative to urine toxicology for use as an outcome measure in cocaine clinical trials.

This study addressed the role of demographic variables, severity of drug dependence, and drug-related problems infacilitating or impeding engagement into a research treatment. Patients were tracked through various stages of entry for the research treatment: phone screening, intake, and randomization to treatment. Results suggested that certain demographic factors put patients more at risk for dropping out at intake and randomization. African-American and unemployed patients were less likely to stay in treatment at both stages, with largest differences at intake. Younger patients were less likely to complete both phases, with bigger differences noted at randomiZation. Patients with more days of cocaine use andpatients referred from advertisements were less likely to keep their intake appointments.

This report describes retention in treatment in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (CCTS), a multi-site trial of four psychosocial treatments for 487 cocaine dependent patients. Younger, African-American, and unemployed patients were retained in treatment for fewer days than their counterparts. African-American patients who lived with a partner were retained in treatment for less time than if they lived alone. Higher psychiatric severity kept men in treatment longer but put women at risk for dropping out sooner. Patients who completed the full treatment used drugs less often than patients who dropped out, but outcome did not differ at each month. Patients in the drug counseling condition stayed in treatment for fewer days than patients in psychotherapy, but they were more likely to be abstinent after dropout. Patients with higher psychiatric severity were more at risk for continuing to use drugs after dropout.

This study investigated whether alcohol use affects baseline characteristics and treatment outcome in 128 adults who participated in a randomized trial of cognitive behavioral vs. 12-step treatment for crack cocaine abuse. Assessments were taken at baseline and weeks 4, 8, 12, and 26 on biologically-verified cocaine abstinence and psychometric measures. Alcohol use was measured at intake and subsequent assessments using the Addiction Severity Index (ASI) and self-reported frequency of alcohol consumption. Results indicate alcohol use at baseline was associated with increased baseline cocaine use and ASI drug severity but was not associated with ASI psychiatric severity, psychiatric diagnoses, or other baseline variables. Alcohol use at baseline did not predict worse treatment outcome for cocaine abstinence. However, alcohol use after four weeks of treatment did predict ability to achieve cocaine abstinence at assessment points during and after treatment.

Aim: The study aimed to assess the efficacy of the Severity of Dependence Scale (SDS) as a diagnostic measure of cocaine dependence and determine the cut-off score that best discriminates between the presence and absence of a DSM-IV diagnosis of cocaine dependence., Design: Cross-sectional survey., Setting: Sydney, Australia., Participants: One hundred and forty-two cocaine users., Measurements: The diagnostic performance of the SDS was measured via ROC analysis against DSM-IV diagnoses of cocaine dependence, as measured by the Composite International Diagnostic Interview (CIDI)., Findings: ROC analysis revealed the SDS to be a test of high diagnostic utility for the measurement of cocaine dependence. The cut-off point on the SDS at which there is optimal discrimination between the presence and absence of a DSM-IV diagnosis of cocaine dependence was found to be 3 (i.e. a score of 3 or more)., Conclusions: The study statistically validated the utility of the SDS as a diagnostic measure of cocaine dependence and has determined an appropriate cut-off point. The SDS is recommended as a brief screening instrument for cocaine dependence that can be used in addition to more comprehensive measures, such as the CIDI.

Objective: Cocaine dependence first appeared as a diagnostic category in 1987 with the publication of DSM-III-R. While the temporal sequencing of alcohol symptoms has a long history, little such attention has been focused on cocaine dependence. This paper examines the retrospective recall of DSM-III-R cocaine dependence symptom progression among a large sample of cocaine users and the relationship of these symptoms to psychiatric comorbidity., Methods: Using data from the US National Comorbidity Survey, DSM-III-R criterion 'A' cocaine dependence symptoms were sequenced temporally based on age of symptom onset. Each of these numerical symptom strings was examined to determine its prevalence and association to comorbid psychiatric disorders., Results: Cocaine users represented 16%, of the sample. Although hundreds of symptom sequence permutations are possible, only a few are highly prevalent. Subjects whose early onset symptoms are neuroadaptive (e.g. tolerance and withdrawal) are more likely to develop cocaine dependence than subjects whose early symptoms are characterized by psychosocial consequences. Furthermore, certain temporal patterns were found to increase or decrease the presence or absence of cocaine dependence and psychiatric comorbidity. Finally, psychiatric comorbidity preceded rather than followed cocaine use onset disproportionately., Conclusions: Like alcohol users, cocaine users follow a limited array of symptom sequence pathways from first use to dependence. By better understanding and examining the temporal progression of drug use symptoms, clinicians might improve screening and assessment activities and determine more effectively the extent of risks associated with continued premorbid drug use and enhance treatment-matching. We encourage clinicians to develop evaluation instruments that specifically ask patients to sequence their cocaine use-related symptoms temporally.

This study addresses the issue of whether the increased rates of substance-related problems for family members of cocaine abusers are specific for each substance. The present analysis examined the prevalence of problems due to alcohol or drug use separately for mothers, fathers, sisters, and brothers using the Family History Assessment Module. The probands were 343 out-of-treatment subjects with DSM-III-R cocaine disorders who did or did not have additional alcohol and opiate disorders. After accounting for age, race, gender, and antisocial personality, family history of alcohol-related problems had an odds ratio of 1.6 (p <.05) if a participant was alcoholic in addition to abusing cocaine. Specifically, a significantly greater proportion of participants' sisters (p <.001) and brothers (p <.05) had alcohol-related problems if the participant had a history of alcoholism. Among probands who reported opiate abuse or dependence, 38% had relatives with drug-related problems, while participants without opiate abuse or dependence had less than 31% of relatives with drug-related problems (p <.05). However, this association with opiate abuse or dependence and family history of drug-related problems was non-significant after controlling for participants' age, race, gender, treatment status, and antisocial personality diagnosis (odds ratio = 1.4, 95% C.I. = 0.8-2.4). Associations between participants' alcoholism and first-degree relatives' drug-related problems (and vice versa) showed that participants' history of opiate addiction did improve prediction of first-degree relatives' alcohol-related problems, except for participants' brothers. Additional familial risks for alcoholism were seen among siblings of drug abusers who also reported abuse of or dependence on alcohol even after controlling for relatives' ages. Furthermore, parental prevalence of alcohol-related problems were greater when participants had opiate addiction in addition to cocaine addiction. This seems to indicate that opiate addiction in addition to cocaine addiction has particularly strong inheritance patterns. In contrast, parental prevalence of drug-related problems was not greater when participants had alcohol addiction in addition to cocaine addiction. Thus, the cross-substance parent-child familial risk is limited to the dually diagnosed illicit drug.

A consecutive series of 100 male cocaine dependent patients were interviewed about suicidal behavior and completed the 34-item Childhood Trauma Questionnaire (CTQ) to determine whether childhood trauma is associated with suicidal behavior in cocaine dependent men. Patients who had attempted suicide (n = 34) reported significantly higher scores for childhood emotional abuse, physical abuse, sexual abuse, and emotional and physical neglect than patients who had never attempted suicide (n = 66). In this study, various childhood traumas were found to be significantly associated withsuicidal behavior among adult male cocaine dependent patients.

While methadone maintenance treatment (MMT) has been demonstrated to be an effective treatment for opiate dependence, its impact on the treatment outcome of other illicit drug abuse is not as clear. Using the initial urine drug screen (UDS) and follow-up UDS at 1, 6, 12, and 24 months, 167 patients consecutively admitted to MMT were evaluated for opiate, sedative (predominantly benzodiazepine), and stimulant (predominantly cocaine) use. Retention for the opiate only group was 97.32 days longer on average than for patients using opiates along with stimulants, sedatives, or both stimulants and sedatives. Patients abusing opiates only had the greatest decrease in drug use; however, MMT was also associated with decreases in cocaine and sedative use over the 24 month follow-up period. There was no evidence that patients "switched" their drugs of abuse with time in treatment. The negative impact of non-opiate drug use on outcome in MMT and its implications for treatment planning are discussed.

This study examined the relationships between lifetime years of cocaine, alcohol, and marijuana use prior to entry into residential treatment for primary cocaine dependence and (a) intake depression levels, and (b) levels of cocaine use in the six months after completing treatment. Years of education, age, and lifetime years of cocaine and alcohol use contributed significantly to predicting depression levels. Lifetime years of alcohol use alone predicted cocaine use during the six months post-treatment.

Aims: The factor structure of DSM-IV substance disorder criteria is examined among alcohol, cannabis, cocaine and opiate users to determine the dimensionality of abuse and dependence criteria within each of these drug classes and whether a common construct can be generalized across drug classes., Design: 12-month criterion prevalence was assessed as part of the World Health Organization's Study on the Reliability and Validity of the Alcohol and Drug Use Disorder Instruments in various settings at eight sites around the world using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). A majority of respondents were recruited from non-treatment settings. In addition to exploratory factor analysis, confirmatory factor analysis was used to analyse factor structures using weighted least square methods and tetrachoric correlation matrices. Multi-sample analysis techniques were used to model differences between drug-classes., Findings: In the full data analyses identified a single factor solution for each user population and across user populations. However, analyses of data from users reporting low to moderate symptomatology identified a two-dimensional construct among alcohol, cannabis and opiate users consisting of a major "dependence" factor and a lesser "abuse" factor. In addition, results showed that neither the abuse criterion "(A2) use in physical hazardous situations" or the dependence criterion "(D7) use despite knowledge of psychological/physical problems" were central to the latent construct in any of the user populations, except for D7 among alcohol users., Conclusions: The multi-dimensional results found among users with low to moderate symptomatology indicate that: (1) previous results from relatively homogeneous populations may have been biased towards lesser order solutions, and that (2) the DSM-IV substance disorder criteria describe at least two distinct phenomena, supporting the current DSM-IV organization of substance disorder criteria. Further work needs to evaluate whether prevalent symptoms are present in random or predictable combinations, whether combinations reflecting a specific hierarchy of severity can be identified, and whether incident symptoms are accumulated in a predictable pattern, within specific user populations and across user populations.

A small, controlled study was conducted to assess whether pergolide mesylate has clinical promise as a treatment for cocaine abuse prior to embarking on a larger, randomized, double-blind, controlled trial. Fourteen individuals were placed on placebo for 2 weeks, followed by a 24-week single-blind study in which they were placed on pergolide for 12 weeks, followed by placebo for 12 weeks. Another 14 patients received single-blind placebo for two weeks and then were randomized into a 24-week double-blind, placebo-controlled, multiple baseline design. Initially, patients enrolled in the study were placed on risperidone (n = 9) or placebo (n = 5). During the first 12 weeks, retention was worse for those receiving pergolide compared to risperidone or placebo. Neither risperidone nor pergolide were more efficacious in reducing cocaine use than placebo. Although earlier open studies found pergolide to show promise as a treatment for cocaine abuse, this study did not support these earlier findings. Comparing an agent to both an active control and placebo group may better predict whether a promising new agent will have clinical utility compared to the standard open trial.

This study evaluated the prevalence of Axis II disorders in substance abuse patients and the relationship between Axis II psychopathology and two other known predictors of adverse addiction treatment outcomes, i.e., Axis I psychiatric comorbidity and illegal drug use, specifically cocaine. 232 patients with cocaine and/or alcohol dependence were admitted to either inpatient or outpatient addiction recovery programs at Carrier Foundation, a nonprofit, private-pay hospital in New Jersey. Axis II disorders were more prevalent in cocaine than alcohol dependence and in patients with Axis I psychiatric comorbidity. When all three predictors were evaluated in one prediction model, the combination of Axis I and II psychopathology was the best predictor of a return to substance use at one year post-treatment, compared to the three factors alone. These findings highlighted the importance of the interrelationship of the relative prognostic value of three known predictors of addiction treatment.

Crack cocaine users are at high risk for HIV, with higher frequency crack users engaging in higher rates of HIV-related sexual risk behaviors. This study will assess the variables impacting changes in crack use frequency. Out-of-treatment crack users were street recruited in East Harlem, NY. Subjects (n = 727) were 33% female, 91% minority, and 28% reported recent drug injecting. Baseline and 6-month follow-up interviews were administered. There was a significant reduction in crack use over time (p < .0001). Subjects were categorized according to five groups, based on their change in level of crack use between the two interviews, to predict those who stopped, maintained, or changed their level of use. Discriminant analyses identified six variables as the best predictors of the five groups, including having been in drug treatment since baseline and having been a drug injector (both related to reduced levels of crack use). The overall reduction in crack use for the sample masked the fact that important subgroups remained at high use levels or increased their use. The identification of subgroups who may be most resistant to reducing drug use can be helpful in developing more effective interventions.