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Background: Our group has established the feasibility of using on-body electrocardiographic (ECG) sensors to detect cocaine use in the human laboratory. The purpose of the current study was to test whether ECG sensors and features are capable of discriminating cocaine use from other non-cocaine sympathomimetics., Methods: Eleven subjects with cocaine use disorder wore the Zephyr BioHarness™ 3 chest band under six experimental (drug and non-drug) conditions, including 1) laboratory, intravenous cocaine self-administration, 2) after a single oral dose of methylphenidate, 3) during aerobic exercise, 4) during tobacco use (N=7 who smoked tobacco), and 5) during routine activities of daily inpatient living (unit activity). Three ECG-derived feature sets served as primary outcome measures, including 1) the RR interval (i.e., heart rate), 2) a group of ECG interval proxies (i.e., PR, QS, QT and QTc intervals), and 3) the full ECG waveform. Discriminatory power between cocaine and non-cocaine conditions for each of the three outcomes measures was expressed as the area under the receiver operating characteristics (AUROC) curve., Results: All three outcomes successfully discriminated cocaine use from unit activity, exercise, tobacco, and methylphenidate conditions with a mean AUROC values ranging from 0.66 to 0.99 and with least squares means values all statistically different/higher than 0.5 among all subjects [F(3, 99) = 3.38, p =0.02] and among those with tobacco use [F(4, 84) = 5.39, p = 0.0007]., Conclusions: These preliminary results support discriminatory power of wearable ECG sensors for detecting cocaine use., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Assessment instruments commonly used in clinical trials to measure functional outcomes in substance users may lack sensitivity to detect change during treatment, potentially limiting findings regarding benefits of reduced drug use. This study evaluated the sensitivity of the Addiction Severity Index (ASI) to detect change in psychiatric functioning among cocaine users., Methods: Data were pooled across five clinical trials for cocaine use disorder (N = 492) that included a 12-week treatment period and 6-month follow-up. Within-person cohen's d' was used to evaluate effect size of change on the Psychiatric Composite Score of the ASI (ASI-Psych) and Global Severity Index (GSI) of the Brief Symptom Inventory, as well as cocaine use., Results: Effect sizes were larger for GSI than ASI-Psych from baseline to week 12 (GSI d' = 0.59; ASI-Psych d' = 0.16), and 6-month follow-up (GSI d' = 0.48; ASI-Psych d' = 0.10). For those with non-zero ASI-Psych at baseline (n = 252), medium effect sizes were found over the 12-week period (d' = 0.53) and 6-month follow-up (d' = 0.47). Effect sizes for change in days of cocaine use were most similar to GSI in either sample., Conclusions: The ASI Psychiatric Composite Score may have limited sensitivity to detect change in psychiatric functioning among clinical trial participants who reduce cocaine use. It may be useful for detecting change amongst those reporting some psychiatric problems at the start of treatment. Future research should consider an instrument's sensitivity to change when assessing the potential functional benefits of reducing cocaine use., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Although previous studies have shown that opioid agonist therapy (OAT) is linked to reductions in illicit opioid use, less is known about how OAT impacts the use of other psychoactive substances. We aimed to examine the changes in use of different substances by comparing patterns before and after initiating OAT., Methods: Data for this study was derived from three ongoing prospective cohorts involving people who use drugs in Vancouver, Canada from 1996 to 2018. We assessed use patterns for heroin, illicit prescription opioid, cocaine, crack cocaine, crystal methamphetamine, cannabis, daily alcohol use, and benzodiazepines. Segmented regression was conducted to compare the trends of substance use between pre-treatment and post-treatment periods., Results: The study included 1107 participants. After OAT engagement, we observed an immediate decline in the proportion as well as a decreasing trend for heroin (Adjusted Odds Ratio (AOR): 0.80, 95% confidence interval (CI): 0.77, 0.83), illicit prescription opioid (AOR: 0.87, 95% CI: 0.83, 0.90), and benzodiazepines (AOR: 0.73, 95 % CI: 0.67, 0.80). There was no significant difference comparing the pre-treatment and post-treatment trends for cocaine, crack cocaine, crystal methamphetamine, and cannabis. However, higher growth slope was noted during the post-treatment period for daily alcohol use (P = 0.016)., Conclusions: We observed significant reduction in illicit opioids use following OAT initiation, but not for stimulant and cannabis. The increasing problematic use of alcohol may pose challenges to the safety and effectiveness of OAT. Development of comprehensive and tailored treatment strategies is needed for poly-substance users accessing OAT., Competing Interests: Declaration of Competing Interest The University of British Columbia has received an unstructured gift from NG Biomed Ltd., a private firm seeking a license to produce medical cannabis, to support Dr. M.-J. Milloy. He is the Canopy Growth professor of cannabis science at the University of British Columbia, a position created using unstructured gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia’s Ministry of Mental Health and Addictions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Despite calls for non-abstinence endpoints in randomized clinical trials (RCTs) for cocaine use disorder, there is a lack of data validating non-abstinence endpoints. We conducted a clinical validation of reduction in cocaine frequency level as a non-abstinence endpoint in RCTs for cocaine use disorder (CUD)., Methods: We utilized a pooled dataset (n = 716; 63.6 % male, 51.4 % non-Hispanic white) from seven RCTs for CUD. We specified three cocaine frequency levels at baseline and end of treatment (EOT): abstinence, low frequency (1-4 days/month), and high frequency (5+ days/month). Multiple regression analyses were conducted., Results: Among the sample, 38.3 % had at least a one-level reduction from baseline to EOT, whereas 61.7 % did not change/increased frequency level. At least a one-level reduction in cocaine frequency level from baseline to EOT versus no change/increase was significantly associated with better functioning up to one year following treatment on measures of cocaine use, as well as psychological, employment, legal, and other drug use problem severity domains of the Addiction Severity Index (ASI). We also conducted analyses only among those at the high frequency level at baseline and found those who reduced to low frequency use at EOT had similar outcomes at follow-up as those who reduced to abstinence., Conclusions: At least a one-level reduction in cocaine frequency level from pretreatment to EOT can be a clinically meaningful endpoint given its relation to sustained clinical benefit up to one-year following treatment. These data parallel recent findings regarding reduction in drinking risk level among individuals with alcohol use disorder., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Persons dually diagnosed with opioid and cocaine dependence (OD + CD) present a clinical challenge and are at risk of morbidity and mortality. The time of escalation of heroin and cocaine exposure in persons with OD + CD remain understudied, and the influence of gender and other variables have not been examined. This observational study focused on the time of escalation of heroin and cocaine in volunteers with OD + CD, examining gender and exposure to other drugs (e.g., cannabis or alcohol) as predictors. Ages of first use and of onset of heaviest use of each drug were collected (in whole years). Time of escalation was defined as the interval between age of first use and onset of heaviest use., Volunteers: sequentially ascertained adult volunteers recruited from the New York Metropolitan area, of which n = 297 were diagnosed with OD + CD., Methods: Instruments administered were the SCID-I diagnostic interview (DSM-IV criteria), BIS-11 impulsiveness scale, and KMSK scales, dimensional measures of maximal exposure to specific drugs., Results: In volunteers with OD + CD, ages of onset of heaviest use of cannabis (median age = 15) and alcohol (median age = 19) were in adolescence or emerging adulthood and preceded those for heroin and cocaine (median ages = 26 and 25, respectively). Maximal levels of cannabis and alcohol exposure were high, in volunteers with OD + CD. In adjusted Cox regressions, gender was not a significant predictor of time of heroin or cocaine escalation. However, more rapid time of alcohol escalation was a predictor of more rapid time of escalation of both heroin and cocaine, in volunteers with OD + CD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Methadone maintenance is an effective treatment for opioid use disorder (OUD), yet many methadone-maintained patients (MMPs) struggle with cocaine use during OUD recovery. The current study aimed to identify whether prefrontal cortex (PFC) activity during a risky decision-making task was associated with cocaine use during a 90-day follow-up in MMPs., Methods: MMPs (N = 28) attended a single neuroimaging session wherein PFC activity was measured using functional near-infrared spectroscopy (fNIRS) during the Balloon Analogue Risk Task (BART). Trait impulsivity was assessed via the Barratt Impulsiveness Scale version 11 (BIS-11). Following the neuroimaging session, MMPs were tracked via electronic health records for 90 days to determine treatment outcomes including cocaine use verified by urine drug screens., Results: During the BART, MMPs who used cocaine displayed increased neural activity in the right PFC during active decision-making (F 1, 22  = 14.75, p = 0.001) and the right dorsolateral PFC during active minus passive decision-making (F 1, 22  = 5.56, p = 0.028) compared to participants who did not use cocaine. Receiver operating characteristic curves confirmed that neural activity in the right PFC during active decision-making (AUC = 0.841, 95% CI, 0.697-0.985, p = 002), and in the right dorsolateral PFC during active minus passive decision-making (AUC = 0.805, 95% CI, 0.643-0.968, p = 0.006) was associated with continued cocaine use. MMPs who used cocaine versus those who did not reported increased trait impulsivity on the BIS-11 Total Score (t=-2.28, p = 0.031)., Conclusions: The fNIRS device is portable, relatively easy to use, and potentially feasible for use in methadone outpatient programs to assess propensity for negative treatment outcomes such as continued cocaine use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Prenatal cocaine exposure (PCE) has been linked to child/adolescent behavior problems and substance use in several longitudinal cohort studies. It is unclear whether these effects extend into adulthood and influence young adult behavior problems and substance use and, if so, whether they are mediated by childhood and adolescent experiences., Methods: These data are from an ongoing longitudinal study of individuals born to women who were recruited early in pregnancy. Trimester-specific data on prenatal drug exposure were obtained. Caregivers and offspring were assessed at delivery and at 1, 3, 7, 10, 15, and 21 years postpartum. This report is from age 21, when 225 offspring (52% females; 54% African American, 46% Caucasian) reported on behavior problems, emotion regulation, and substance use., Results: There were significant direct associations between PCE and early initiation of marijuana, 21-year emotion regulation problems, arrest history, and Conduct Disorder. The relation between PCE and young adult internalizing behavior was mediated by adolescent mood symptoms. The association between PCE and 21-year marijuana use was mediated by early initiation of marijuana use., Conclusions: PCE has both direct and indirect long-term associations with young adult development. Using statistical models that considered the complex interrelationships among PCE and adult outcomes, we demonstrated that the direct effects of PCE on young adult emotion regulation problems, arrest history, and Conduct Disorder are not completely explained by earlier adolescent behavior. Moreover, the analyses suggesting mediated pathways from PCE to young adult problems identify crucial variables to target interventions for exposed children and adolescents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Since 2000, heroin use patterns have shifted within the United States. How this change may relate to polydrug use among local heroin users is unknown. Although polydrug use has been studied, user perceptions of drug use in terms of health risks, arrest risk, availability, cost, liking, and dependence have not been considered., Methods: Data are presented from a brief, face-to-face survey conducted in 2016 of 200 non-in-treatment heroin users from Cleveland, OH. We assessed the use of and attitudes on alcohol, marijuana, methamphetamine, heroin, crack cocaine, powder cocaine, and prescription drugs. We estimated polydrug (concurrent past month) use with cluster analysis and latent profiles. Regression analysis estimated the strength of relationships between attitudes and frequency of use., Results: We identified five clusters: Cluster 1 used heroin concomitantly with alcohol and occasionally crack; Cluster 2 used heroin and crack cocaine daily; Cluster 3 used heroin daily and almost exclusively; Cluster 4 used heroin and marijuana daily; and Cluster 5 were part-time drug users. Drug use frequency was associated with liking and being anxious when drugs could not be obtained. High perceived availability of heroin and cocaine and low cost facilitated polydrug use., Conclusions: Understanding polydrug use clusters among heroin users is important for addressing the larger opioid epidemic. Users' perceptions of a drug's availability and cost appeared to facilitate polydrug use and justify more detailed future research on drug access., (Copyright © 2018. Published by Elsevier B.V.)

Background: Polysubstance use (PSU) is prevalent among individuals with substance use disorders, but the vast majority of preclinical substance use research has focused on individual substances in isolation. Cocaine has been prevalent in the repertoire of persons who use more than one illicit substance., Methods: We conducted a meta-analysis combining results from literature searches and secondary data analyses to estimate the prevalence of simultaneous and concurrent cocaine + alcohol and cocaine + cannabis use among cocaine users. We next summarized the small body of literature on behavioral, cognitive and neurobiological consequences of cocaine PSU across species, with a focus on alcohol and cannabis. Finally, we used systematic literature searches to assess the extent to which human and animal studies on the neurobiological consequences of cocaine include PSU subjects., Results: The estimated prevalence of simultaneous and concurrent alcohol use among human cocaine users was 74% and 77%, respectively. The estimated prevalence of simultaneous and concurrent cannabis use among cocaine users was 38% and 64%, respectively. Consumption of alcohol or cannabis with cocaine enhances subjective responses to cocaine, concomitant with changes in cocaine metabolism that increase blood cocaine levels, and, in the case of alcohol, produce the psychoactive metabolite cocaethylene. There is also consistent evidence for neurobiological effects of cocaine + alcohol combinations. However, animal PSU research with cocaine lags behind human research., Conclusion: Based on the prevalence and known consequences of PSU, consideration of PSU in both human and animal research is vital for understanding patterns of substance use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cocaine abuse has been reported as leading to impaired cognitive function. However, cocaine abusers commonly also abuse alcohol, which can itself produce cognitive impairment. This study, therefore, aimed to examine the potential confounding effect of alcohol abuse on neuropsychological test performance in cocaine and alcohol abusing individuals, comparing them with individuals who abused alcohol alone and non-abusing controls., Methods: Nineteen cocaine abusers who also met DSM-IV criteria for alcohol abuse/dependence (14 m, 5f; mean age 38.65 ± 3.83) and 20 matched individuals who met criteria for alcohol abuse/dependence alone (12 m, 8f; mean age 38.19 ± 4.82) were administered a battery of neuropsychological tests covering executive function, memory, language and visual/visuospatial function after two to four weeks of abstinence. Nineteen matched healthy controls (8 m, 11f; mean age 37.01 ± 5.98) were also tested., Results: Both the cocaine + alcohol group and the alcohol group performed significantly more poorly than the healthy controls on the executive (ESs 2.13 and 2.57) and memory tests (ESs 0.58 and 1.06). The findings were similar for language (ESs 0.92 and 1.69), where the cocaine + alcohol abusers additionally performed significantly better than the alcohol abusers. Both patient groups were impaired on two of the five tests of visual/visuospatial function, with better performance by the cocaine + alcohol group on one of them., Conclusions: Chronic cocaine abuse does not appear from this study to be associated with cognitive impairment over and above that which can be attributed to co-existent alcohol abuse., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Urine adulteration is a concern among patients treated for opioid use disorder. Quantitative urine testing for buprenorphine (B) and norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can facilitate constructive conversations with patients that may lead to modifications in the treatment plan, and strengthening of the patient-provider relationship., Case Summary: Three cases are presented in which discordant urine B and NB levels were recognized. Each patient was submerging buprenorphine/naloxone strips in their urine to mask ongoing illicit drug use. The authors used an approach to addressing intentional adulteration of urine samples that adheres to the principles of harm-reduction, the centrality of the patient-provider relationship, and the acknowledgment that ongoing illicit drug use and subsequent dishonesty about disclosure may be common among persons with substance use disorders. Each of the three patients ultimately endorsed diluting their urine, which allowed for strengthening of the patient-provider relationship and modifications to their treatment plans. Two of the three patients stabilized and achieved abstinence, while the third was eventually referred to a methadone treatment program., Conclusion: Providers should routinely monitor B and NB levels, rather than qualitative screening alone, and discordant levels should elicit a timely conversation with the patient. The authors use of a nonjudgmental approach to address urine adulteration, including giving patients an opportunity to reflect on potential solutions, has been effective at helping patients and providers to reestablish a therapeutic alliance and maintain retention in treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Most recent research on adolescent drug use has focused on alcohol, tobacco, and marijuana. Less is known about the recent epidemiology of adolescent cocaine use, which has serious health consequences., Purpose: To describe recent trends in cocaine use by U.S. high school students, and identify differences in lifetime and repeated use across sex and racial/ethnic groups., Methods: We used data from the national Youth Risk Behavior Surveys (YRBS) from 1999 to 2015. We estimated the prevalence of lifetime cocaine use (LCU) and repeated lifetime cocaine use (RLCU) across years by race/ethnicity and sex and tested for linear and quadratic trends., Results: The prevalence of LCU decreased from 1999 to 2015 (9.54%-5.19%). RLCU also decreased (5.13%-2.84%). Despite the overall decline, LCU and RLCU both rose between 2009-2015 (LCU:2.78%-5.19%, RLCU:1.58%-2.84%). Boys had higher rates of LCU and RLCU than girls (LCU:6.42% vs 4.65%; RLCU:3.69% vs 2.18%). American Indian/Alaskan Native, Native Hawaiian/Pacific Islander, and Hispanic adolescents had the highest overall prevalence of LCU. Black adolescents' LCU patterns differed from other racial/ethnic groups. The prevalence of LCU among Black boys increased over time, while the prevalence for Black girls remained consistently low., Conclusions: Adolescent cocaine use is less common today than in the 1990s. However, rates of adolescent cocaine use have risen across all racial/ethnic groups in the past few years. Public health efforts should address at risk groups with particularly high or rising rates of cocaine use., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Attentional bias towards substance-related stimuli has shown to be involved in the development and maintenance of cocaine dependence. The relationship between alcohol use and cocaine dependence shown in literature justify the need of study these two substances jointly., Methods: This paper analyzes patterns of attentional bias in 71 patients with cocaine dependence and compares these patterns according to whether occasional or problematic concurrent alcohol use is taken into account. It also analyzes whether attentional bias towards alcohol and cocaine-related stimuli predicts treatment retention. Attentional bias was evaluated with a visual probe task between 15 and 20days after admission to treatment. Treatment status was recorded at a three-month follow-up. Severity of dependence and cocaine and alcohol craving were also measured., Results: Results show that patients with cocaine dependence and problematic alcohol use show a pattern of approach towards alcohol stimuli (M=8.32, SD=27.01). In contrast, patients with cocaine dependence with occasional consumption of alcohol exhibit a pattern of avoidance of such stimuli (M=-7.23, SD=19.20) (t=2.79, p=0.007). Logistic regression indicates that alcohol attentional bias is the only variable with predictive capacity (OR=1.05, 95% CI=[1.01, 1.09]). It should also be noted that there is a pattern of avoidance of alcohol stimuli in patients who drop out of treatment., Conclusion: The results of this study suggest the need to delve into whether therapeutic strategies involving deeper emotional processing or avoidance strategies are more suitable for preventing relapse., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis., Methods: Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis., Results: Robust regression analyses showed that (1) duration of protease inhibitor (PI) use was independently associated with myocardial and hepatic triglyceride contents, (2) duration of PI use was independently associated with myocardial triglyceride in cocaine users (p=0.025), but not in cocaine never-users (p=0.84), and (3) duration of PI use was independently associated with hepatic triglyceride in cocaine users, but not in cocaine never-users (p=0.52)., Conclusions: Cocaine use may trigger/exacerbate the toxicity of PI in ART-associated myocardial and hepatic steatosis, suggesting that cocaine abstinence/reduced use may retard these ART-associated comorbidities. Clinical trials should be conducted to examine whether reduced cocaine use improves HIV/AIDS-associated myocardial and hepatic steatosis., (Copyright © 2017. Published by Elsevier B.V.)

Background: Altered sensitivity to positive and negative outcomes may be linked to the maladaptive choices characteristic of substance use disorders. Few studies have determined the distinct roles that positive and negative outcomes play in stimulus-response learning in cocaine users. The purpose of the present study was to investigate sensitivity to learning from positive and negative outcomes on a probabilistic learning task in cocaine users employing human laboratory and crowdsourcing techniques., Methods: Individuals who reported cocaine use were recruited for a laboratory study (Experiment 1) or an online study on Amazon.com's Mechanical Turk (mTurk) (Experiment 2). All participants completed a feedback-based probabilistic learning task in which images were classified into categories (A versus B). Positive and negative outcomes were provided in a probabilistic manner on separate trials. Proportion of optimal responses and response times were recorded., Results: Active cocaine users were less sensitive to learning from positive relative to negative outcomes. These effects were consistent across image type and session in the laboratory sample. Similarly, reduced sensitivity to learning from positive outcomes was observed in cocaine users on mTurk. Control participants did not show suboptimal performance following positive or negative outcomes., Conclusions: This study extends the limited research on feedback-based learning in drug users by demonstrating reduced sensitivity to positive outcomes in cocaine users recruited in the human laboratory and online. Future studies on the clinical significance and mechanisms underlying this bias are needed to understand its relevance as a target for intervention development., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: TV-1380 (AlbuChE) is a novel recombinant fusion protein of mutated butyrylcholinesterase (BChE) that has increased catalytic efficiency for cocaine metabolism compared to wild-type BChE., Methods: Intra-muscular injections of TV-1380 (150mg or 300mg) or placebo were administered once weekly to participants (n=66-69 per group) in a randomized, double-blind study to evaluate the ability of TV-1380 to facilitate abstinence in treatment-seeking, cocaine-dependent individuals. The primary endpoint was the proportion of participants achieving abstinence from cocaine during the last three weeks of the 12 week treatment phase, based on daily self-report of "no use" confirmed by urine testing., Results: Although there were no significant differences between the TV-1380 treatment groups and placebo for the primary endpoint, 6% of participants in the 150mg and 300mg TV-1380 groups and no participants in the placebo group achieved abstinence. For the only declared secondary endpoint, there was a dose-dependent increase in the group mean percentage of urine samples testing negative for cocaine metabolites during weeks 5-12 (8.1% and 14.6% for the 150mg and 300mg TV-1380 groups, respectively, compared to 4.7% for the placebo group; p=0.0056 for 300mg vs. placebo). No meaningful differences in adverse events were seen between treatment groups., Conclusions: While the apparent reduction in cocaine use may be of insufficient magnitude to justify further trials of TV-1380 in cocaine dependence, the results argue for development of improved enzymes with greater catalytic activity., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: Cocaine abuse is capable of activating the innate immune system in the CNS resulting in deregulation of homeostasis between pro and antiinflammatory cytokines. The aim of this study was to investigate serum levels of pro and antiinflammatory cytokines, IL-6 and IL-10 respectively, in cocaine users from a young population-based sample., Methods: This is a case-control study nested in a cross-sectional population-based survey, with individuals of 18 and 35 years old. Two groups were selected: 24 healthy controls and 12 subjects who reported cocaine use. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit., Results: There was a statistically significant increase in IL-6 (p=0.037) and decrease in IL-10 (p=0.007) serum levels, between cocaine users and the control group. There was also an increase in the ratio IL-6/IL-10 (p=0.013) among cocaine users individuals, when compared to the control group., Conclusions: Our results suggest that cocaine users showed an activation of the immune system when compared a control group, demonstrating a disruption in the balance of pro and antiinflammatory cytokines. Thus, peripheral cytokines may represent a putative biomarkers for cocaine users, contributing to the development of diagnosis and effective treatments., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Prenatal cocaine exposure (PCE) is associated with increased rates of illicit-substance use during adolescence. In addition, both PCE and illicit-substance use are associated with alterations in cortico-striato-limbic neurocircuitry, development of which is ongoing throughout adolescence. However, the relationship between illicit-substance use, PCE and functional neural responses has not previously been assessed concurrently., Methods: Sixty-eight adolescents were recruited from an ongoing longitudinal study of childhood and adolescent development. All participants had been followed since birth. Functional magnetic resonance imaging (fMRI) data were acquired during presentation of personalized stressful, favorite-food and neutral/relaxing imagery scripts and compared between 46 PCE and 22 non-prenatally-drug-exposed (NDE) adolescents with and without lifetime illicit-substance use initiation. Data were analyzed using multi-level ANOVAs (pFWE<.05)., Results: There was a significant three-way interaction between illicit-substance use, PCE status and cue condition on neural responses within primarily cortical brain regions, including regions of the left and right insula. Among PCE versus NDE adolescents, illicit-substance use was associated with decreased subcortical and increased cortical activity during the favorite-food condition, whereas the opposite pattern of activation was observed during the neutral/relaxing condition. Among PCE versus NDE adolescents, illicit-substance use during stress processing was associated with decreased activity in cortical and subcortical regions including amygdala, hippocampus and prefrontal cortex. Neural activity within cortico-striato-limbic regions was significantly negatively associated with subjective ratings of anxiety and craving among illicit-substance users, but not among non-users., Conclusions: These findings suggest different neural substrates of experimentation with illicit drugs between adolescents with and without in utero cocaine exposure., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Cocaine has become one of the drugs of most concern in Switzerland, being associated with a wide range of medical, psychiatric and social problems. Available treatment options for cocaine dependence are rare. The study sought to compare combined prize-based contingency management (prizeCM) plus cognitive-behavioral therapy (CBT) to CBT alone in cocaine-dependent patients., Methods: Sixty cocaine-dependent patients participated in a randomized, controlled trial with two treatment conditions. The participants were randomly assigned to the experimental group (EG; n = 29), who received CBT combined with prizeCM, or to the control group (CG; n = 31), who received CBT only during 24 weeks. The primary outcome measures were retention, at least 3 consecutive weeks of cocaine abstinence, the maximum number of consecutive weeks of abstinence and proportions of cocaine-free urine samples during the entire 24-week and at 6-month follow-up., Results: Sixty-three percent of the participants completed the study protocol. Participants in both groups significantly reduced cocaine use over time. Overall, no difference in cocaine-free urine screens was found across the two treatment groups, except at weeks 8, 9, 10, 17 and 21 in favor of the EG., Conclusions: The addition of prizeCM to CBT seems to enhance treatment effects, especially in the early treatment period, supporting results from previous studies. Both the combined intervention and CBT alone, led to significant reductions in cocaine use during treatment and these effects were sustained at 6-month follow-up. These findings underline the importance in implementing CM and CBT interventions as treatment options for cocaine dependence in the European context., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Introduction: The autobiographical Implicit Association Test (aIAT) is a variant of the Implicit Association Test reportedly capable of detecting an individual's concealed autobiographical event with very high accuracy. A previous attempt to utilize this measurement technique for the identification of cocaine users rendered an alarming rate of false positives. In this study, we aimed to explore the potential reasons behind the measurement's inaccuracy., Methods: Two versions of the cocaine aIAT were devised with different category labels (descriptive 'guilty/innocent' and self-referenced 'as if you were/were not'). Forty-one cocaine abstinent participants (43.9% male; mean age = 28.17 ± 7.36) were randomly assigned to one of the two conditions. Self-declared cocaine abstinence was confirmed for the 12-month period preceding data collection through hair analysis. Participants were also administered bespoke implicit and explicit cocaine user attitude measures, the self-esteem IAT and the Rosenberg self-esteem scale., Results: The category labels which elicited self-referenced knowledge showed low accuracy (19%) compared to the 65% of the 'guilty/innocent' labels proposed by original authors. The self-referenced aIAT version significantly correlated with the self-concept measures. The aIAT outcomes were independent from attitudes toward cocaine users., Conclusions: Category labels play an influential role in determining the test's accuracy, demonstrating that participants' propositional knowledge and self-concept are involved during test performance. The aIAT does not appear to tap directly into an individual's implicit memory when relevant memory is not available. Although the test cannot be recommended for detecting drug use, further research should investigate underlying mechanisms and other potentials of the technique., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Individuals with gambling or substance-use disorders exhibit similar functional alterations in reward circuitry suggestive of a shared underlying vulnerability in addictive disorders. Additional research into common and unique alterations in reward-processing in substance-related and non-substance-related addictions may identify neural factors that could be targeted in treatment development for these disorders., Methods: To investigate contextual reward-processing in pathological gambling, a slot-machine fMRI task was performed by three groups (with pathological gambling, cocaine dependence and neither disorder; N = 24 each) to determine the extent to which two groups with addictions (non-substance-related and substance-related) showed similarities and differences with respect to each other and a non-addicted group during anticipatory periods and following the delivery of winning, losing and 'near-miss' outcomes., Results: Individuals with pathological gambling or cocaine dependence compared to those with neither disorder exhibited exaggerated anticipatory activity in mesolimbic and ventrocortical regions, with pathological-gambling participants displaying greater positive possible-reward anticipation and cocaine-dependent participants displaying more negative certain-loss anticipation. Neither clinical sample exhibited medial frontal or striatal responses that were observed following near-miss outcomes in healthy comparison participants., Conclusions: Alterations in anticipatory processing may be sensitive to the valence of rewards and content-disorder-specific. Common and unique findings in pathological gambling and cocaine dependence with respect to anticipatory reward and near-miss loss processing suggest shared and unique elements that might be targeted through behavioral or pharmacological interventions in the treatment of addictions., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Despite extensive research on gender differences in addiction, there are relatively few published reports comparing treatment outcomes for women versus men based on evidence-based treatments evaluated in randomized clinical trials., Methods: An aggregate sample comprised of data from five randomized clinical trials of treatment for cocaine dependence (N = 434) was evaluated for gender differences in clinical outcomes. Secondary analyses compared gender differences in outcome by medication condition (disulfiram versus no medication) and across multiple behavioral treatment conditions., Results: Women, compared with men, had poorer treatment outcomes on multiple measures of cocaine use during treatment and at post-treatment follow-up. These results appear to be primarily accounted for by disulfiram being less effective in women compared with men. There was no evidence of meaningful gender differences in outcome as a function of the behavioral therapies evaluated., Conclusions: These findings suggest that women and men may benefit to similar degrees from some empirically validated behavioral treatments for addiction. Conversely, some addiction pharmacotherapies, such as disulfiram, may be associated with poorer outcomes among women relative to men and point to the need for careful assessment of pharmacological treatments in both sexes prior to widespread clinical implementation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Stimuli associated with cocaine use capture attention. Evidence suggests that fixation time measured on the visual probe task is a valid measure of cocaine cue attentional bias. The aim of this experiment was to demonstrate the test-retest reliability of cocaine cue attentional bias as measured by fixation time during the visual probe task., Methods: In a within-subject, repeated-measures design, thirty-six non-treatment seeking cocaine-using adults completed a visual probe task with eye tracking., Results: Participants displayed an attentional bias to cocaine-related images as measured by fixation time across two occasions (F (1, 35) = 56.5, p < 0.0001). A Pearson correlation indicated significant test-retest reliability for this effect (r = 0.51, p = 0.001). Response time failed to detect an attentional bias and test-retest reliability was low (r = 0.24, p = 0.16)., Conclusion: Fixation time during the visual probe task is a reliable measure of cocaine cue attentional bias in cocaine-using adults across time., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Long-term and early-onset cannabis consumption are implicated in subsequent substance- related problems. The aim of this follow-up study was to investigate whether these patterns of cannabis use could impact cocaine withdrawal severity and cocaine craving intensity during detoxification. In addition, we investigated their impact in the rehospitalization rates due to cocaine dependence 2.5 years after detoxification assessment., Methods: The sample was composed of 93 female cocaine-dependent inpatients who were enrolled in an inpatient detoxification unit. Cocaine withdrawal symptoms were measured at the 4th, 9th and 14th days of detoxification using the cocaine selective severity assessment (CSSA). Data on the age of first years of drug use - alcohol, cannabis and cocaine - and the years of substance abuse were obtained using the Addiction Severity Index (ASI-6). Other relevant clinical variables were also investigated, including a 2.5 years follow-up assessment of number of rehospitalization due to cocaine dependence., Results: Early-onset cannabis use and long-term cannabis abuse were associated with an increase instead of a reduction in the severity of cocaine withdrawal symptoms and craving intensity during detoxification. In addition, long-term cannabis abuse predicted higher number of rehospitalization due to cocaine dependence after 2.5 years of the first detoxification assessment., Conclusions: Early-onset cannabis use and long-term cannabis abuse are associated with a worse detoxification treatment response. Our findings may help to identify patients who will struggle more severely to control cocaine withdrawal syndrome during early drug abstinence, and indicate that cannabis use prior to cocaine withdrawal should be considered an adverse factor., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Trait impulsivity is commonly associated with cocaine dependence. The few studies that have investigated the relation between trait impulsivity and cortical morphometry, have shown a distinct relation between impulsivity and cortical volume (CV) of temporal, frontal and insula cortex. As CV is the function of cortical surface area (SA) and cortical thickness (CT) impulsivity may be differently associated to SA than to CT., Method: Fifty-three cocaine users (CU) and thirty-five controls (HC) (males aged 18-55 years) completed the Barrat impulsiveness scale and a structural scan was made on a 3T MRI scanner. CV, SA and CT were measured using Freesurfer. Multivariate analysis was used to test for group differences and group by impulsivity interaction effects in CV, SA and ST across nine regions of interest in the temporal, frontal and insular cortices. Possible confounding effects of drug- and alcohol exposure were explored., Results: Compared to HC, CU had a smaller SA of the superior temporal cortex but a larger SA of the insula. There were divergent relations between trait impulsivity and SA of the superior temporal cortex and insula (positive in HC, negative in CU) and CT of the anterior cingulate cortex (negative in HC, positive in CU). Within CU, there was a negative association between monthly cocaine use and CT of the insula and superior temporal cortex., Discussion: The distinct relation between trait impulsivity and cortical morphometry in CU and HC might underlie inefficient control over behavior resulting in maladaptive impulsive behaviour such as cocaine abuse., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Selection of an appropriate indictor of treatment response in clinical trials is complex, particularly for the various illicit drugs of abuse. Most widely used indicators have been selected based on expert group recommendation or convention rather than systematic empirical evaluation. Absence of an evidence-based, clinically meaningful index of treatment outcome hinders cross-study evaluations necessary for progress in addiction treatment science., Method: Fifteen candidate indicators used in multiple clinical trials as well as some proposed recently are identified and discussed in terms of relative strengths and weaknesses (practicality, cost, verifiability, sensitivity to missing data). Using pooled data from five randomized controlled trials of cocaine dependence (N=434), the indicators were compared in terms of sensitivity to the effects of treatment and relationship to cocaine use and general functioning during follow-up., Results: Commonly used outcome measures (percent negative urine screens; percent days of abstinence) performed relatively well in that they were sensitive to the effects of the therapies evaluated. Others, including complete abstinence and reduction in frequency of use, were less sensitive to effects of specific therapies and were very weakly related to cocaine use or functioning during follow-up. Indicators more strongly related to cocaine use during follow-up were those that reflected achievement of sustained periods of abstinence, particularly at the end of treatment., Conclusions: These analyses did not demonstrate overwhelming superiority of any single indicator, but did identify several that performed particularly poorly. Candidates for elimination included retention, complete abstinence, and indicators of reduced frequency of cocaine use., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Native Americans experience some of the highest rates of DSM-IV stimulant dependence (SD) of all U.S. ethnic groups. This report compares DSM-IV and DSM-5 stimulant use disorder (SUD) diagnostic criteria in an American Indian community sample., Methods: Demographic information, stimulant (methamphetamine or cocaine) use, and lifetime DSM-IV and DSM-5 diagnoses were assessed in 858 adult American Indians. Item Response Theory (IRT) analyses were used to assess SUD criteria in both DSM-IV and DSM-5 criteria sets along an underlying latent trait severity continuum and the effect of demographic variables on differential item functioning (DIF) in those criteria., Results: The overall rate of DSM-IV SD was 33%, of DSM-IV SUD was 38%, and of DSM-5 SUD was 36% with no gender differences. All SUD symptoms in both the DSM-IV and DSM-5 datasets functioned on the moderate portion of the underlying severity continuum. "Craving" discriminated better than any other criterion at its level of severity in indicating the presence or absence of SUD. There was little DIF in groups defined by gender or any other demographic variable in either the DSM-IV or DSM-5 datasets., Conclusions: These findings indicate that in this American Indian sample, diagnostic criteria for DSM-IV and DSM-5 SUD function similarly in terms of severity and DIF and that the abolition of the DSM-IV distinction between stimulant abuse and dependence in DSM-5 is warranted., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Former sleep studies among non-treatment seeking chronic cocaine users had captured polysomnographic changes for as long as three weeks of abstinence., Methods: 20 cocaine dependent participants, randomized to placebo in an ongoing clinical trial, received 12 days of inpatient substance abuse treatment followed by 6 weeks of outpatient cognitive behavioral therapy. Polysomnographic recording was performed on consecutive nights during the 1st and 2nd inpatient and 3rd and 6th outpatient weeks. Number of days abstinent was determined from thrice weekly urine toxicology and self-report. Polysomnographic sleep was compared between study week 1 and 2, using paired t-tests. Trajectory of total sleep time (TST) was modeled both as a linear and a quadratic function of days abstinent., Results: Despite reporting an improvement in overall sleep quality, polysomnographic sleep worsened from week 1 to 2. Among all participants, TST and stage 2 sleep time decreased, while REM sleep latency increased. Among participants who began the study with a positive urine test, there was also a decrease in REM and a trend for decreased slow wave sleep. TST compared to number of days abstinent (up to 54 days) was best fit with a quadratic model (p=0.002), suggesting the possibility of an improvement in total sleep time with extended abstinence., Conclusions: This is the first polysomnographic characterization of sleep in a large sample of cocaine users in treatment. Present findings confirm earlier results of poor and deteriorating sleep early in abstinence, and raise the possibility of improvement after an extended abstinence., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Examined effects of prenatal cocaine exposure (PCE) on tobacco, alcohol, marijuana and cocaine use by age 15., Methods: Adolescent (n=358; 183 PCE, 175 non-prenatally cocaine exposed; NCE) drug use was assessed using urine, hair, and/or blood spot samples and self-report (Youth Risk Behavior Surveillance System; YRBSS) at ages 12 and 15. Logistic regression assessed effects of PCE on drug use controlling for other drug exposures, environment and blood lead levels (BLL)., Results: Adjusted percentages of drug use (PCE vs. NCE) were: tobacco 35% vs. 26% (p<.04), marijuana 33% vs. 23% (p<.04), alcohol 40% vs. 35% (p<.01), and any drugs 59% vs. 50% (p<.005). PCE adolescents were twice as likely to use tobacco (OR=2.02, 95% CI=1.05-3.90, p<.04), 2.2 times more likely to use alcohol (OR=2.16, 95% CI=1.21-3.87, p<.01) and 1.8 times more likely to use marijuana (OR=1.81, 95% CI=1.02-3.22, p<.04) than NCE adolescents. A race-by-cocaine-exposure interaction (p<.01) indicated PCE non-African American adolescents had greater probability of tobacco use (65%) than NCE non-African American youth (21%). PCE was associated with any drug use (OR=2.16, CI=1.26-3.69, p<.005), while higher BLL predicted alcohol use (p<.001). Violence exposure was a predictor of tobacco (p<.002), marijuana (p<.0007) and any drug (p<.04)., Conclusions: PCE and exposure to violence increased the likelihood of tobacco, marijuana or any drug use by age 15, while PCE and higher early BLL predicted alcohol use. Prevention efforts should target high risk groups prior to substance use initiation., (Copyright © 2013. Published by Elsevier Ireland Ltd.)

Background: Magnetic resonance imaging has provided a wealth of information on altered brain activations and structures in individuals addicted to cocaine. However, few studies have considered the influence of age and alcohol use on these changes., Methods: We examined gray matter volume with voxel based morphometry (VBM) and low frequency fluctuation (LFF) of BOLD signals as a measure of cerebral activity of 84 cocaine dependent (CD) and 86 healthy control (HC) subjects. We performed a covariance analysis to account for the effects of age and years of alcohol use., Results: Compared to HC, CD individuals showed decreased gray matter (GM) volumes in frontal and temporal cortices, middle/posterior cingulate cortex, and the cerebellum, at p<0.05, corrected for multiple comparisons. The GM volume of the bilateral superior frontal gyri (SFG) and cingulate cortices were negatively correlated with years of cocaine use, with women showing a steeper loss in the right SFG in association with duration of use. In contrast, the right ventral putamen showed increased GM volume in CD as compared to HC individuals. Compared to HC, CD individuals showed increased fractional amplitude of LFF (fALFF) in the thalamus, with no significant overlap with regions showing GM volume loss., Conclusions: These results suggested that chronic cocaine use is associated with distinct changes in cerebral structure and activity that can be captured by GM volume and fALFF of BOLD signals., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Markers of chronic cocaine exposure on neural mechanisms in animals and humans is of great interest. The probabilistic reversal-learning task may be an effective way to examine dysfunction associated with cocaine addiction. However the exact nature of the performance deficits observed in cocaine users has yet to be disambiguated., Method: Data from a probabilistic reversal-learning task performed by 45 cocaine users and 41 controls was compared and fit to a Bayesian hidden Markov model (HMM)., Results: Cocaine users demonstrated the predicted performance deficit in achieving the reversal criterion relative to controls. The deficit appeared to be due to excessive switching behavior as evidenced by responsivity to false feedback and spontaneous switching. This decision-making behavior could be captured by a single parameter in an HMM and did not require an additional parameter to represent perseverative errors., Conclusions: Cocaine users are characterized by excessive switching behavior on the reversal-learning task. While there may be a compulsive component to behavior on this task, impulsive decision-making may be more relevant to observed impairment. This is important in building diagnostic tools to quantify the degree to which each type of dysfunction is present in individuals, and may play a role in developing treatments for those dysfunctions., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Ascertaining agreement between DSM-IV and DSM-5 is important to determine the applicability of treatments for DSM-IV conditions to persons diagnosed according to the proposed DSM-5., Methods: Data from a nationally representative sample of US adults were used to compare concordance of past-year DSM-IV opioid, cannabis, cocaine and alcohol dependence with past-year DSM-5 disorders at thresholds of 3+, 4+, 5+ and 6+ positive DSM-5 criteria among past-year users of opioids (n=264), cannabis (n=1622), cocaine (n=271) and alcohol (n=23,013). Substance-specific 2 × 2 tables yielded overall concordance (kappa), sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV)., Results: For DSM-IV alcohol, cocaine and opioid dependence, optimal concordance occurred when 4+ DSM-5 criteria were endorsed, corresponding to the threshold for moderate DSM-5 alcohol, cocaine and opioid use disorders. Maximal concordance of DSM-IV cannabis dependence and DSM-5 cannabis use disorder occurred when 6+ criteria were endorsed, corresponding to the threshold for severe DSM-5 cannabis use disorder. At these optimal thresholds, sensitivity, specificity, PPV and NPV generally exceeded 85% (>75% for cannabis)., Conclusions: Overall, excellent correspondence of DSM-IV dependence with DSM-5 substance use disorders was documented in this general population sample of alcohol, cannabis, cocaine and opioid users. Applicability of treatments tested for DSM-IV dependence is supported by these results for those with a DSM-5 alcohol, cocaine or opioid use disorder of at least moderate severity or severe cannabis use disorder. Further research is needed to provide evidence for applicability of treatments for persons with milder substance use disorders., (Published by Elsevier Ireland Ltd.)

Background: Severe mental illness is often exclusionary criteria for studies examining factors that influence addiction treatment outcome. Therefore, little is known about predictors of treatment response of individuals receiving psychosocial treatments for addictions who suffer from co-occurring severe mental illness., Methods: The impact of demographic, substance abuse severity, psychiatric severity, and service utilization variables on in-treatment performance (i.e., longest duration of abstinence) in a 12-week contingency management (CM) intervention for stimulant abuse in 96 severely mentally ill adults was investigated. A 4-step linear regression was used to identify independent predictors of in-treatment abstinence., Results: This model accounted for 37.4% of variance in the longest duration of abstinence outcome. Lower levels of stimulant use (i.e., stimulant-negative urine test) and psychiatric severity (i.e., lower levels of psychiatric distress), as well as higher rates of outpatient treatment utilization at study entry were independently associated with longer duration of drug abstinence., Conclusion: These data suggest that individuals with low levels of stimulant use and psychiatric severity, as well as those actively engaged in services are most likely to succeed in a typical CM intervention. For others, modifications to CM interventions, such as increasing the value of reinforcement or adding CM to evidence based psychiatric interventions may improve treatment outcomes., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Medications decreasing central noradrenergic activity have been associated with attenuation of cocaine effects., Aims: This pilot study examined the efficacy of doxazosin versus placebo for reducing cocaine use in treatment-seeking cocaine dependent persons., Methods: We screened 108 cocaine dependent subjects and assigned 35 participants to receive either doxazosin (8mg/day) or placebo for 13 weeks. Participants were titrated on the study medication according to two different schedules. During the initial phase of the study, patients were titrated onto the study medication over an 8-week period (DOX-slow). After reviewing data from our human laboratory study, a second phase was initiated, wherein titration was accelerated to a 4-week period (DOX-fast). All participants received weekly cognitive behavioral therapy. Urine toxicology was performed thrice weekly., Results: Baseline subject characteristics were comparable. Thirty subjects entered the study: 8 subjects in DOX-slow, 9 subjects in DOX-fast, and 13 subjects in placebo. Total number of cocaine-negative urines was significantly increased in the DOX-fast group; and percentage of total cocaine-negative urines by group were 10% for DOX-slow group, 35% for DOX-fast group, and 14% for placebo (χ(2)=36.3, df=2, p<0.0001). The percentage of participants achieving two or more consecutive weeks of abstinence by group was 0% for DOX-slow group, 44% for DOX-fast group, and 7% for placebo (χ(2)=7.35, df=2, p<0.023)., Conclusions: This pilot study suggests the potential efficacy of doxazosin when rapidly titrated in reducing cocaine use., (Published by Elsevier Ireland Ltd.)

Background: Contingency management (CM) is efficacious for reducing drug use, but it has rarely been applied to patients with severe and persistent mental health problems. This study evaluated the efficacy of CM for reducing cocaine use in psychiatric patients treated at a community mental health center., Methods: Nineteen cocaine-dependent patients with extensive histories of mental health problems and hospitalizations were randomized to twice weekly urine sample testing with or without CM for 8 weeks. In the CM condition, patients earned the chance to win prizes for each cocaine-negative urine sample. Patients also completed an instrument assessing severity of psychiatric symptoms pre- and post-treatment., Results: Patients assigned to CM achieved a mean (standard deviation) of 2.9 (1.7) weeks of continuous cocaine abstinence versus 0.6 (1.7) weeks for patients in the testing only condition, p=.008, Cohen's effect size d=1.35. Of the 16 expected samples, 46.2% (27.5) were cocaine negative in the CM condition versus 13.8% (27.9) in the testing only condition, p=.02, d=1.17, but proportions of negative samples submitted did not differ between groups. Reductions in psychiatric symptoms were noted over time in CM, but not the testing only, condition, p=.02., Conclusions: CM yielded benefits for enhancing durations of abstinence in dual diagnosis patients, and it also was associated with reduced psychiatric symptoms. These findings call for larger-scale and longer-term evaluations of CM in psychiatric populations., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Identifying variables that predict drug use in treatment-seeking drug addicted individuals is a crucial research and therapeutic goal. This study tested the hypothesis that choice to view cocaine images is associated with concurrent and prospective drug use in cocaine addiction., Methods: To establish choice-concurrent drug use associations, 71 cocaine addicted subjects (43 current users and 28 treatment seekers) provided data on (A) choice to view cocaine images and affectively pleasant, unpleasant, and neutral images [collected under explicit contingencies (when choice was made between two fully visible side-by-side images) and under more probabilistic contingencies (when choice was made between pictures hidden under flipped-over cards)]; and (B) past-month cocaine and other drug use. To establish choice-prospective drug use associations, 20 of these treatment-seeking subjects were followed over the next 6 months., Results: Baseline cocaine-related picture choice as measured by both tasks positively correlated with subjects' concurrent cocaine and other drug use as driven by the actively-using subjects. In a subsequent multiple regression analysis, choice to view cocaine images as compared with affectively pleasant images (under probabilistic contingencies) was the only predictor that continued to be significantly associated with drug use. Importantly, this same baseline cocaine>pleasant probabilistic choice also predicted the number of days drugs were used (cocaine, alcohol, and marijuana) over the next 6 months., Conclusions: Simulated cocaine choice - especially when probabilistic and when compared with other positive reinforcers - may provide a valid laboratory marker of current and future drug use in cocaine addiction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Methadone maintenance for heroin dependence reduces illicit drug use, crime, HIV risk, and death. Typical dosages have increased over the past few years, based on strong experimental and clinical evidence that dosages under 60 mg/day are inadequate and that dosages closer to 100mg/day produce better outcomes. However, there is little experimental evidence for the benefits of exceeding 100 mg/day, or for individualizing methadone dosages. We sought to provide such evidence., Methods: We combined individualized methadone dosages over 100 mg/day with voucher-based cocaine-targeted contingency management (CM) in 58 heroin- and cocaine-dependent outpatients. Participants were randomly assigned to receive a fixed dose increase from 70 mg/day to 100mg/day, or to be eligible for further dose increases (up to 190 mg/day, based on withdrawal symptoms, craving, and continued heroin use). All dosing was double-blind. The main outcome measure was simultaneous abstinence from heroin and cocaine., Results: We stopped the study early due to slow accrual. Cocaine-targeted CM worked as expected to reduce cocaine use. Polydrug use (effect-size h=.30) and heroin craving (effect-size d=.87) were significantly greater in the flexible/high-dose condition than in the fixed-dose condition, with no trend toward lower heroin use in the flexible/high-dose participants., Conclusions: Under double-blind conditions, dosages of methadone over 100mg/day, even when prescribed based on specific signs and symptoms, were not better than 100mg/day. This counterintuitive finding requires replication, but supports the need for additional controlled studies of high-dose methadone., (Published by Elsevier Ireland Ltd.)

Background: Cocaine 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., Methods: This 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 (80 mg/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., Results: Survival analysis revealed no differences in study retention between the two groups, with approximately 56% of subjects completing the 12-week study (Cox analysis χ(2) = .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 (χ(2) = 0.2, p = .66; OR = 0.89 [95% CI 0.41-1.74]). Atomoxetine was generally well tolerated in this population., Conclusions: These data provide no support for the utility of atomoxetine in the treatment of cocaine dependence., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans., Methods: Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N=300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors., Results: Participants assigned to OP received, on average, 3.67 (SD=1.30)h of counseling per active week in treatment. IOP participants received an average of 5.23 (SD=1.68)h of counseling per active week (less than the anticipated 9h per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p=.67) or cocaine dependence (p=.63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps>.05)., Conclusions: Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) will soon replace the DSM-IV, which has existed for nearly two decades. The changes in diagnostic criteria have important implications for research and for the clinical care of individuals with Substance Use Disorders (SUDs)., Methods: We used the Semi-Structured Assessment for Drug Dependence and Alcoholism to evaluate the lifetime presence of DSM-IV abuse and dependence diagnoses and DSM-5 mild, moderate, or severe SUDs for alcohol, cocaine, opioids, and cannabis in a sample of 7,543 individuals recruited to participate in genetic studies of substance dependence., Results: Switches between diagnostic systems consistently resulted in a modestly greater prevalence for DSM-5 SUDs, based largely on the assignment of DSM-5 diagnoses to DSM-IV "diagnostic orphans" (i.e., individuals meeting one or two criteria for dependence and none for abuse, and thus not receiving a DSM-IV SUD diagnosis). The vast majority of these diagnostic switches were attributable to the requirement that only two of 11 criteria be met for a DSM-5 SUD diagnosis. We found evidence to support the omission from DSM-5 of the legal criterion due to its limited diagnostic utility. The addition of craving as a criterion in DSM-5 did not substantially affect the likelihood of an SUD diagnosis., Conclusion: The greatest advantage of DSM-5 for the diagnosis of SUDs appears to be its ability to capture diagnostic orphans. In this sample, changes reflected in DSM-5 had a minimal impact on the prevalence of SUD diagnoses., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Frontal systems dysfunction is present in stimulant-dependent patients. However, it is unclear whether this dysfunction is a pre-morbid risk factor or stimulant-induced, is severe enough to be clinically relevant, and if it is relevant to treatment response. These questions were addressed using the Frontal Systems Behavior Scale (FrSBe), a reliable and valid self-report assessment of three neurobehavioral domains associated with frontal systems functioning (Apathy, Disinhibition, and Executive Dysfunction, summed for a Total), that assesses both pre- and post-morbid functioning, and has a specific cutoff for defining clinically significant abnormalities., Method: Six sites evaluating 12-step facilitation for stimulant abusers obtained the FrSBe from 180 methamphetamine- and/or cocaine-dependent participants. Dichotomous treatment response measures included self-reported stimulant use, stimulant urine drug screens, and treatment completion., Results: A substantial percentage of participants retrospectively reported clinically significant neurobehavioral abnormalities prior to lifetime stimulant abuse initiation (e.g., 67.5% on FrSBe-Total) with a significant increase in the proportion reporting such abnormalities for current functioning (86% on FrSBe-Total; p<0.0001). Treatment response was significantly worse for participants with, relative to those without, clinically significant Disinhibition as measured by treatment non-completion (31.6% vs. 15.6%, OR=2.51) and self-reported stimulant use during treatment (40.5% vs. 16.7%, OR=3.40)., Conclusion: These findings suggest that frontal systems dysfunction is present prior to stimulant-abuse onset and worsens with stimulant use. Disinhibition may be a prime target for intervention in stimulant-dependent individuals., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The μ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR)., Methods: The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations., Results: The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53 × 10(-5); n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 × 10(-7)) (p-values non-FDR corrected)., Conclusion: The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Prior research has demonstrated the dimensionality of alcohol, nicotine and cannabis use disorders criteria. The purpose of this study was to examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription drug abuse and dependence criteria and to determine the impact of elimination of the legal problems criterion on the information value of the aggregate criteria., Methods: Factor analyses and Item Response Theory (IRT) analyses were used to explore the unidimensionality and psychometric properties of the illicit drug use criteria using a large representative sample of the U.S. population., Results: All illicit drug abuse and dependence criteria formed unidimensional latent traits. For amphetamines, cocaine, sedatives, tranquilizers and opioids, IRT models fit better for models without legal problems criterion than models with legal problems criterion and there were no differences in the information value of the IRT models with and without the legal problems criterion, supporting the elimination of that criterion., Conclusion: Consistent with findings for alcohol, nicotine and cannabis, amphetamine, cocaine, sedative, tranquilizer and opioid abuse and dependence criteria reflect underlying unitary dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the American Psychiatric Association's DSM-5 Substance and Related Disorders Workgroup., (Published by Elsevier Ireland Ltd.)

Background: A number of changes have been proposed and investigated in the criteria for substance use disorders in DSM-5. However, although clinical utility of DSM-5 is a high priority, relatively little of the empirical evidence supporting the changes was obtained from samples of substance abuse patients., Methods: Proposed changes were examined in 663 patients in treatment for substance use disorders, evaluated by experienced clinicians using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). Factor and item response theory analysis was used to investigate the dimensionality and psychometric properties of alcohol, cannabis, cocaine and heroin abuse and dependence criteria, and craving., Results: The seven dependence criteria, three of the abuse criteria (hazardous use; social/interpersonal problems related to use; neglect of roles to use), and craving form a unidimensional latent trait for alcohol, cannabis, cocaine and heroin. Craving did not add significantly to the total information offered by the dependence criteria, but adding the three abuse criteria and craving together did significantly increase total information for the criteria sets associated with alcohol, cannabis and heroin., Conclusion: Among adult patients in treatment for substance disorders, the alcohol, cannabis, cocaine and heroin criteria for dependence, abuse (with the exception of legal problems), and craving measure a single underlying dimension. Results support the proposal to combine abuse and dependence into a single diagnosis in the DSM-5, omitting legal problems. Mixed support was provided for the addition of craving as a new criterion, warranting future studies of this important construct in substance use disorders., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: Craving is a hallmark of addiction and characterized by obsessive thoughts about, and compulsive urges to use, a substance. While craving is frequently thought of as primarily being a feature of acute withdrawal, there is evidence to suggest that it increases in strength over extended periods of abstinence. While several measures are available to assess acute craving states, there remains a lack of clinical measures appropriate for capturing the enduring cognitive aspects of urges to use drugs. The present study was designed to develop and validate a measure of obsessive-compulsive thoughts in cocaine-dependent individuals., Methods: The proposed 14-item Obsessive Compulsive Cocaine Use Scale (OCCUS) was administered to 107 individuals: 55 participants meeting diagnostic criteria for cocaine dependence and 52 recreational users of cocaine. In addition to the OCCUS, participants also completed the Drug Abuse Screening Test, Cocaine Craving Questionnaire-Now, and Social Desirability Scale of the California Personality Inventory., Results: Results of confirmatory factor analysis indicated that the OCCUS fit the two-factor structure of the Obsessive Compulsive Drinking Scale on which it was based, independently assessing the "obsessive" and "compulsive" aspects of cocaine dependence. The OCCUS demonstrated good internal consistency reliability and convergent, discriminant, and criterion validity., Conclusion: The proposed measure is a promising step towards the successful capture of the long-term cognitive features of craving for cocaine via self-report, and should represent a useful tool for clinical and research use., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Cocaine dependence is associated with cognitive deficits and altered task-related cerebral activation in cognitive performance (see Li and Sinha, 2008, for a review). Relatively little is known whether these individuals are also impaired in regional brain activation of the default mode network (DMN). We demonstrated previously that greater activation of the default brain regions precedes errors in a stop signal task performed by healthy controls (SST, Li et al., 2007). We seek to determine whether individuals with cocaine dependence are impaired in DMN activity, specifically activity preceding error, as compared to the healthy people. We also examine the relation to years of cocaine use., Methods: Individuals with cocaine dependence (CD, n=23) and demographics-matched healthy controls (HC, n=27) performed a SST that employed a tracking procedure to adjust the difficulty of stop trials and elicit errors approximately half of the time. Blood oxygenation level dependent (BOLD) signals of go trials preceding stop error as compared to those preceding stop success trials were extracted with generalized linear models using statistical parametric mapping., Results: HC showed activation of bilateral precuneus and posterior cingulate cortices and ventromedial prefrontal cortex (vmPFC) preceding errors during the SST. In contrast, despite indistinguishable stop signal performance, CD did not show these error predicting activations. Furthermore, the effect size of error-preceding vmPFC activation was inversely correlated with years of cocaine use., Conclusions: These findings indicate DMN deficits and could potentially add to our understanding of the effects of chronic cocaine use on cerebral functions in cocaine dependence. Work to further clarify potential changes in functional connectivity and gray matter volume is warranted to understand the relevance of DMN to the pathology of cocaine misuse., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Although DSM-IV criteria are widely used in making diagnoses of substance use disorders, gaps exist regarding diagnosis classification, use of dependence criteria, and effects of measurement bias on diagnosis assessment. We examined the construct and measurement equivalence of diagnostic criteria for cocaine and opioid dependences, including whether each criterion maps onto the dependence construct, how well each criterion performs, how much information each contributes to a diagnosis, and whether symptom-endorsing is equivalent between demographic groups., Methods: Item response theory (IRT) and multiple indicators-multiple causes (MIMIC) modeling were performed on a sample of stimulant-using methadone maintenance patients enrolled in a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN) (N=383). Participants were recruited from six community-based methadone maintenance treatment programs associated with the CTN and major U.S. providers. Cocaine and opioid dependences were assessed by DSM-IV Checklist., Results: IRT modeling showed that symptoms of cocaine and opioid dependences, respectively, were arrayed along a continuum of severity. All symptoms had moderate to high discrimination in distinguishing drug users between severity levels. "Withdrawal" identified the most severe symptom of the cocaine dependence continuum. MIMIC modeling revealed some support for measurement equivalence., Conclusions: Study results suggest that self-reported symptoms of cocaine and opioid dependences and their underlying constructs can be measured appropriately among treatment-seeking polysubstance users.

Background: The study evaluated, among cocaine users, the hypothesized positive association of depression and concurrent cocaine use and impairment, alcohol use and impairment, and general drug use and impairment. The hypothesis that gender would moderate these associations, with women showing a stronger correlation between depression and measures of substance use and impairment, was also tested. Also examined was the association of depression with future cocaine use and impairment and substance use treatment participation., Methods: Empirical reports on adult cocaine users published in English in peer-reviewed journals since 1986 that contained data on depression and substance use outcome(s) were obtained using a systematic search. Studies that placed restrictions on range of depression scores to select the sample, experiments that administered cocaine to subjects, and trials of antidepressant medications were excluded. The search yielded 60 studies for the analysis including 53 reports that collected data from clinical venues and seven that were community-based., Results: As hypothesized, the analyses showed that depression is associated with concurrent cocaine-, alcohol-, and general drug use and impairment. Effect sizes were small. Hypothesized moderating effects of gender were not supported. Depression was not associated, at a statistically significant level, with treatment participation or future cocaine use and impairment., Conclusions: Depression is consistently but modestly associated with measures of cocaine-, alcohol-, and general drug use and impairment among cocaine users. Associations of depression with treatment participation and with future cocaine use and impairment are not immediately evident, although limitations of data warrant cautious interpretation.

Crack cocaine is a highly addictive drug. To learn more about crack addiction, long-term crack smokers who had never met the DSM-IV criteria for lifetime cocaine dependence were compared with those who had. The study sample consisted of crack users (n=172) from the Dayton, Ohio, area who were interviewed periodically over 8 years. Data were collected on a range of variables including age of crack initiation, frequency of recent use, and lifetime cocaine dependence. Cocaine dependence was common with 62.8% of the sample having experienced it. There were no statistically significant differences between dependent and non-dependent users for age of crack initiation or frequency of crack use. In terms of sociodemographics, only race/ethnicity was significant, with proportionally fewer African-Americans than whites meeting the criteria for cocaine dependence. Controlling for sociodemographics, partial correlation analysis showed positive, statistically significant relationships between lifetime cocaine dependence and anti-social personality disorder, attention deficit/hyperactivity disorder, and lifetime dependence on alcohol, cannabis, amphetamine, sedative-hypnotics, and opioids. These results highlight the importance addressing race/ethnicity and comorbid disorders when developing, implementing, and evaluating interventions targeting people who use crack cocaine. Additional research is needed to better understand the role of race/ethnicity in the development of cocaine dependence resulting from crack use.