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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 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.)

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.

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.

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.

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.

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.

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.

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.

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.

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.