Diagnosis Of Cocaine Dependence Research Articles

Bidirectional influence of heroin and cocaine escalation in persons with dual opioid and cocaine dependence diagnoses.

Persons with dual severe opioid and cocaine use disorders are at risk of considerable morbidity, and the bidirectional relationship of escalation of mu-opioid agonists and cocaine use is not well understood. The aim of this study was to examine the bidirectional relationship between escalation of heroin and cocaine use in volunteers dually diagnosed with opioid and cocaine dependence (OD + CD). Volunteers from New York with OD + CD (total n = 295; male = 182, female = 113; age ≥ 18 years) were interviewed with the Structured Clinical Interview for the DSM-IV Axis I Disorders and Kreek-McHugh-Schluger-Kellogg scales for dimensional measures of drug exposure, which also collect ages of 1st use and onset of heaviest use. Time of escalation was defined as age of onset of heaviest use minus age of 1st use in whole years. Times of escalation of heroin and cocaine were positively correlated in both men (Spearman r = .34, 95% confidence interval [CI: .17, .48], p < .0001) and women (Spearman r = .51, [.27, .50], p < .0001) volunteers. After we adjusted for demographic variables, a Cox regression showed that time of cocaine escalation was a predictor of time of heroin escalation (hazard ratio [HR] = 0.97, 95% CI [0.95, 0.99], p = .003). Another Cox regression showed that this relationship is bidirectional, because time of heroin escalation was also a predictor of time of cocaine escalation (HR = 0.98, [0.96-0.99], p = .016). In these adjusted models, gender was not a significant predictor of time of escalation of either heroin or cocaine. Therefore, escalation did not differ robustly by gender when adjusting for demographics and other major variables. Overall, rapid escalation of cocaine use was a predictor of rapid escalation of heroin use, and vice versa, in persons with dual severe opioid and cocaine use disorders. These findings suggest a shared vulnerability to rapid escalation of these 2 drugs in persons with dual severe opioid and cocaine use disorders. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Analyses of polymorphisms of intron 2 of OPRK1 (kappa-opioid receptor gene) in association with opioid and cocaine dependence diagnoses in an African-American population

RationaleThe dynorphin/kappa-opioid receptor (KOR) system (encoded by PDYN and OPRK1 genes respectively) is highly regulated by repeated exposure to drugs of abuse, including mu-opioid agonists and cocaine. These changes in the dynorphin/KOR system can then influence the rewarding effects of these drugs of abuse. Activation of the dynorphin/KOR system is also thought to have a role in the pro-addictive effects of stress. Recent in vitro assays showed that the OPRK1 intron 2 may function as a genomic enhancer in the regulation KOR expression, and contains a glucocorticiod-responsive sequence site. We hypothesize that SNPs in intron 2 of OPRK1 are associated with categorical opioid or cocaine dependence diagnoses, as well as with dimensional aspects of drug use (i.e., magnitude of drug exposure). MethodsThis study includes 577 subjects ≥ 18 years old, with African ancestry (AA) from the USA. They were divided into three groups: 152 control subjects, 142 persons with lifetime opioid dependence diagnosis (OD), and 283 subjects with lifetime cocaine dependence diagnosis (CD). Five SNPs (rs16918909, rs7016778, rs997917, rs6473797, rs10111937) that span 10 Kb nucleotides in intron 2 of OPRK1 were used for the association analyses. Genotyping was performed with the Smokescreen® array or sequencing of PCR-amplified DNA fragments. Association analyses for OD and CD diagnoses and the OPRK1 intron 2 alleles were carried out with Fisher’s exact test. The Kreek-McHugh-Schluger-Kellogg (KMSK) scales were used for dimensional measure of maximum exposure to specific drugs, using Mann-Whitney tests. ResultsTwo SNPs, rs997917 and rs10111937 showed point-wise significant allelic association (p < 0.05) with CD diagnosis, and rs10111937 showed a point-wise significance in association with OD. None of these single SNP associations with categorical diagnoses were significant after correction for multiple testing (pcorr > 0.05). However, significant associations of several genotype patterns (diplotypes) were found with cocaine dependence, but none for opioid dependence. The most significant genotype pattern with cocaine dependence diagnosis occurred for rs6473797 and rs10111937 (pcorr = 0.036, odds ratio = 1.92, FDR < 0.05), and survived correction for multiple testing. Dimensional analyses with KMSK scores show that persons with either rs997917 or rs10111937 variants had greater exposure to cocaine, compared to those with prototype allele (Mann-Whitney tests, point-wise). ConclusionsThis study provides additional support of potential importance of regulatory regions of intron 2 of the OPRK1 gene in development of cocaine and opioid dependence diagnoses, in a population with African-American ancestry.

Association of Serotonin Transporter (SERT) Polymorphisms with Opioid Dependence and Dimensional Aspects of Cocaine Use in a Caucasian Cohort of Opioid Users.

IntroductionA functional tandem repeat polymorphism in the promoter of the serotonin transporter (SERT) gene (SLC6A4) has been studied for association to neuropsychiatric conditions, including substance use disorders. Short (S) forms of this repeat result in reduced transcription, and presumably greater synaptic levels of serotonin, which are involved in opioid and cocaine-induced reward. Dual exposure to heroin and cocaine is a common pattern of poly-drug use and is associated with considerable morbidity. We hypothesize that SLC6A4 variants are associated with cocaine exposure in subjects with an opioid dependence diagnosis (OD), and also in non-dependent opioid users (NOD). Other single nucleotide polymorphisms (SNPs) of SLC6A4 may also be likewise associated.Materials and MethodsThis study determined whether variants of the SLC6A4 promoter repeats and two intronic SNPs, rs16965628 and rs2066713, are associated with categorical diagnoses of opioid dependence (DSM-IV criteria) and with dimensional aspects of cocaine use, in a Caucasian cohort (n=591). Three groups of subjects were examined: (1) 276 subjects with opioid dependence diagnosis (OD); (2) 163 subjects who had used opioids for non-medical reasons but never had an opioid dependence diagnosis (NOD); (3) 152 healthy controls (HC).ResultsAside from high exposure to heroin in the OD group, relatively high exposure to cocaine was detected in both OD and NOD groups. The SERT repeat genotype (classified as “long-long” [LL] versus ”short-long” plus “short-short” [SL+SS]) was not associated with categorical opioid dependence diagnoses. A nominally significant association was identified with the [SL+SS] genotype of SLC6A4 and cocaine KMSK scores ≥“cutpoint” for a cocaine dependence diagnosis (p=0.026). The [SL+SS] genotype was associated with more rapid cocaine escalation than the LL genotype. No significant associations of rs16965628 and rs2066713 SNPs were found overall.ConclusionThe functional SERT promoter tandem repeat genotype may be associated to heavy cocaine exposure and more rapid escalation of cocaine use, in persons with and without opioid dependence diagnosis.

Altered power spectra in antisocial males during rest as a function of cocaine dependence: A network analysis

Abnormalities in the spectral power of offenders’ neural oscillations have been noted within select Resting-State Networks (RSNs); however, no study has yet evaluated the influence of cocaine dependence, drug use severity, and psychopathic traits on these abnormalities. To this end, the present study compared rest-related power spectral characteristics between two groups of offenders (with and without a DSM-IV-TR cocaine-dependence diagnosis) and a non-offender control group. Results indicated that both offender groups presented with lower low frequency power ratio (LFPR) scores (i.e. across all RSNs) than non-offenders. These differences in LFPR scores were due to both higher high-frequency power (0.15-0.25 Hz; within seven (in non-dependent offenders) and five (in cocaine-dependent offenders) of eight investigated networks) and decreased low-frequency power (0.01-0.10 Hz; within six (in non-dependent offenders) and one (in cocaine-dependent offenders) of eight investigated networks) compared to non-offenders. Thus, both cocaine-dependent and non-dependent offenders displayed abnormal neural oscillations, suggesting that these oscillatory abnormalities could exist as neurobiological features associated with offender status. Offenders’ LFPR levels correlated with lifetime years of cocaine use, but not with the level of psychopathic traits. These findings supplement our knowledge regarding the influence of substance use on resting-state activity in offenders; moreover, they provide further indication of the importance of evaluating shared/unique variance associated with drug use and pyschopathic personality traits.

Are trait impulsivity and exposure to cannabis or alcohol associated with the age of trajectory of cocaine use? A gender-specific dimensional analysis in humans with cocaine dependence diagnosis.

Cocaine use disorders (CUD) cause major morbidity and optimized prevention efforts are critical. It is unclear if trait impulsivity and exposure to cannabis or alcohol are associated with age trajectory of cocaine use (e.g., age of onset of heaviest use, or time of escalation), or with vulnerability to develop a CUD. This is an observational study with volunteers (≥ 18 years old), from a metropolitan area. The sample (n = 1,010) included: n = 360 normal volunteers, n = 438 with cocaine dependence (CD) diagnoses, and n = 212 with other addictive diseases. Trait impulsivity was examined with BIS-11 scores. Maximal self-exposure to cannabis, alcohol, and cocaine were characterized dimensionally with Kreek-McHugh-Schluger-Kellogg (KMSK) scales. Time of escalation was defined as the interval between age of first use and age of onset of heaviest use. Onset of maximal use of cannabis (median age = 17) and alcohol (median age = 21) preceded that of cocaine (median age = 27), in volunteers with CD. Multivariate Cox regressions in volunteers with CD show that increasing self-exposure to cannabis was a predictor of earlier onset of heaviest use of cocaine. Also, more rapid time of escalation of alcohol was a predictor of more rapid time of escalation of cocaine. A multiple logistic regression shows that increasing self-exposure to cannabis or alcohol was a positive predictor of odds of CD diagnosis. Trait impulsivity and gender were not significant predictors in these multivariate analyses. This study shows that aspects of adolescent exposure to nonmedical cannabis and alcohol are predictors of early onset of CUD, and may be potentially targeted for prevention efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Interpersonal problems of cocaine dependent adults differ from those of a normative sample

Our research examined patterns of interpersonal problems in patients with a primary diagnosis of cocaine dependence (CD), comparing them with those in a normative sample. We hypothesized that the patterns of individuals with CD would reveal constellations of interpersonal problems distinct from those of the sample, not only at baseline, but also at termination of treatment. Analysis was conducted on 402 CD patients from the training and the main trial phases of the National Institute on Drug Abuse Collaborative Cocaine Treatment Study. Responses to the Inventory for Interpersonal Problems were analyzed—from baseline, from month one, and at treatment termination—according to the Interpersonal Circumplex Model and were compared to the normative sample. The CD sample was described using four distinct subtypes, named according to their relative angular displacement at baseline and highest two subscale means: Cold and Socially Avoidant, Vindictive and Domineering, Overly Nurturant and Intrusive, Nonassertive and Exploitable. Each subtype remained distinct across treatment and consistently reported different types of interpersonal difficulties than the normative population at termination, consistent with the interpersonal pathoplasticity model. In all subtypes, overall interpersonal distress decreased over the course of treatment, to the extent that by treatment termination they were no more or less distressed than the normative sample. These findings have important clinical implications. The interpersonal challenges of patients struggling with addiction to cocaine warrant clinical attention, beyond mediating levels of distress.

Acceptance and present-moment awareness in psychiatric disorders: Is mindfulness mood dependent?

The aim of the present study was to determine 1) whether deficits in two mindfulness dimensions (present-centered awareness and acceptance) were present in individuals with different psychiatric conditions and 2) whether co-existing depressive symptoms affected the mindfulness-related capacities in these groups. A total of 246 individuals, both clinical and non-clinical participants, were included in this study. The clinical sample consisted of 162 individuals; of these, 43 had a diagnosis of cocaine dependence while the remaining 119met clinical criteria for eating disorders (n = 43), major depressive disorder in remission (n = 39), and borderline personality disorder (n = 45). A non-clinical (NC) community sample consisting of 76 individuals was included as a control group. All participants completed self-report instruments to assess present-centered awareness, acceptance, and depressive symptoms. Present-centered awareness scores were significantly associated with depressive symptoms but not with the diagnostic group. By contrast, a significant effect of depressive symptoms and diagnostic group was associated with acceptance scores, with all clinical groups presenting significantly lower scores than the NC sample. These findings suggest that the association between psychopathology, mindfulness, and depressive symptoms varies depending on the specific aspect of mindfulness aspect (i.e., awareness or acceptance) evaluated.

Non-medical Cannabis Self-Exposure as a Dimensional Predictor of Opioid Dependence Diagnosis: A Propensity Score Matched Analysis.

Background: The impact of increasing non-medical cannabis use on vulnerability to develop opioid use disorders has received considerable attention, with contrasting findings. A dimensional analysis of self-exposure to cannabis and other drugs, in individuals with and without opioid dependence (OD) diagnoses, may clarify this issue.Objective: To examine the age of onset of maximal self-exposure to cannabis, alcohol, cocaine, and heroin, in volunteers diagnosed with OD, using a rapidly administered instrument (the KMSK scales). To then determine whether maximal self-exposure to cannabis, alcohol, and cocaine is a dimensional predictor of odds of OD diagnoses.Methods: This outpatient observational study examined maximal self-exposure to these drugs, in volunteers diagnosed with DSM-IV OD or other drug diagnoses, and normal volunteers. In order to focus more directly on opioid dependence diagnosis as the outcome, volunteers who had cocaine dependence diagnoses were excluded. Male and female adults of diverse ethnicity were consecutively ascertained from the community, and from local drug treatment programs, in 2002–2013 (n = 574, of whom n = 94 had OD diagnoses). The age of onset of maximal self-exposure of these drugs was examined. After propensity score matching for age at ascertainment, gender, and ethnicity, a multiple logistic regression examined how increasing self-exposure to non-medical cannabis, alcohol and cocaine affected odds of OD diagnoses.Results: Volunteers with OD diagnoses had the onset of heaviest use of cannabis in the approximate transition between adolescence and adulthood (mean age = 18.9 years), and onset of heaviest use of alcohol soon thereafter (mean age = 20.1 years). Onset of heaviest use of heroin and cocaine was detected later in the lifespan (mean ages = 24.7 and 25.3 years, respectively). After propensity score matching for demographic variables, we found that the maximal self-exposure to cannabis and cocaine, but not to alcohol, was greater in volunteers with OD diagnoses, than in those without this diagnosis. Also, a multiple logistic regression detected that increasing self-exposure to cannabis and cocaine, but not alcohol, was a positive predictor of OD diagnosis.Conclusions/Importance: Increasing self-exposure to non-medical cannabis, as measured with a rapid dimensional instrument, was a predictor of greater odds of opioid dependence diagnosis, in propensity score-matched samples.

Double-blind evaluation of homeopathy on cocaine craving: a randomized controlled pilot study

BackgroundBrazil is among the nations with the greatest rates of annual cocaine usage. Pharmacological treatment of cocaine addiction is still limited, opening space for nonconventional interventions. Homeopathic Q-potencies of opium and Erythroxylum coca have been tested in the integrative treatment of cocaine craving among homeless addicts, but this setting had not proven feasible, due to insufficient recruitment. ObjectiveThis study investigates the effectiveness and tolerability of homeopathic Q-potencies of opium and E. coca in the integrative treatment of cocaine craving in a community-based psychosocial rehabilitation setting. Design, setting, participants, and interventionsA randomized, double-blind, placebo-controlled, parallel-group, eight-week pilot trial was performed at the Psychosocial Attention Center for Alcohol and Other Drugs (CAPS-AD), Sao Carlos/SP, Brazil. Eligible subjects included CAPS-AD patients between 18 and 65 years of age, with an International Classification of Diseases-10 diagnosis of cocaine dependence (F14.2). The patients were randomly assigned to two treatment groups: psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca (homeopathy group), and psychosocial rehabilitation plus indistinguishable placebo (placebo group). Main outcome measuresThe main outcome measure was the percentage of cocaine-using days. Secondary measures were the Minnesota Cocaine Craving Scale and 12-Item Short-Form Health Survey scores. Adverse events were reported in both groups. ResultsThe study population comprised 54 patients who attended at least one post-baseline assessment, out of the 104 subjects initially enrolled. The mean percentage of cocaine-using days in the homeopathy group was 18.1% (standard deviation (SD): 22.3%), compared to 29.8% (SD: 30.6%) in the placebo group (P < 0.01). Analysis of the Minnesota Cocaine Craving Scale scores showed no between-group differences in the intensity of cravings, but results significantly favored homeopathy over placebo in the proportion of weeks without craving episodes and the patients’ appraisal of treatment efficacy for reduction of cravings. Analysis of 12-Item Short-Form Health Survey scores found no significant differences. Few adverse events were reported: 0.57 adverse events/patient in the homeopathy group compared to 0.69 adverse events/patient in the placebo group (P = 0.41). ConclusionsA psychosocial rehabilitation setting improved recruitment but was not sufficient to decrease dropout frequency among Brazilian cocaine treatment seekers. Psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca were more effective than psychosocial rehabilitation alone in reducing cocaine cravings. Due to high dropout rate and risk of bias, further research is required to confirm our findings, with specific focus on strategies to increase patient retention. Trial registrationRBR-2xzcwz (http://www.ensaiosclinicos.gov.br).

Relationship between craving and plasma leptin concentrations in patients with cocaine addiction

BackgroundThere is robust evidence indicating an overlap between neurobiological circuitry and pathways that regulate addictions and those that regulate appetite and food intake. Rodent work suggests a role of the appetitive peptide leptin in cocaine-seeking behaviours. The goal of this study was to investigate the possible relationship between plasma leptin concentrations and cocaine craving and use in patients seeking treatment for cocaine dependence. MethodsPatients (N=43) with a DSM-IV diagnosis of cocaine dependence were studied before starting detoxification (baseline; T0) and then again 14days after (T1; only those patients who abstained from cocaine during the study). Blood samples for plasma leptin concentrations were collected and cocaine craving was assessed using the Brief Cocaine Craving Questionnaire (Brief-CCQ). Food craving was also assessed using a food Visual Analogue Scale (f-VAS). Barratt Impulsiveness Scale (BIS) was used to evaluate impulsivity. ResultsPlasma leptin concentrations at T0 significantly correlated with baseline Brief-CCQ scores (r=0.34, p<0.05). Furthermore, plasma leptin concentrations at T1 significantly correlated with the baseline amount of cocaine used (r=0.5, p<0.05). There were no significant correlations between plasma leptin concentrations and f-VAS scores either at T0 or T1 (p’s>0.05). ConclusionsThe present study suggests a potential relationship between plasma leptin concentrations and cocaine craving and use. Future mechanistic studies are needed to determine whether manipulations of leptin signalling may lead to novel pharmacological approaches to treat cocaine addiction.

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

Addictions to heroin or to cocaine are associated with substantial psychiatric comorbidity, including depression. Poly-drug self-exposure (eg, to heroin, cocaine, cannabis, or alcohol) is also common, and may further affect depression comorbidity. This case-control study examined the relationship of exposure to the above drugs and depression comorbidity. Participants were recruited from methadone maintenance clinics, and from the community. Adult male and female participants (n = 1,201) were ascertained consecutively by experienced licensed clinicians. The instruments used were the SCID-I, and Kreek-McHugh-Schluger-Kellogg (KMSK) scales, which provide a rapid dimensional measure of maximal lifetime self-exposure to each of the above drugs. This measure ranges from no exposure to high unit dose, high frequency, and long duration of exposure. A multiple logistic regression with stepwise variable selection revealed that increasing exposure to heroin or to cocaine was associated greater odds of depression, with all cases and controls combined. In cases with an opioid dependence diagnosis, increasing cocaine exposure was associated with a further increase in odds of depression. However, in cases with a cocaine dependence diagnosis, increasing exposure to either cannabis or alcohol, as well as heroin, was associated with a further increase in odds of depression. This dimensional analysis of exposure to specific drugs provides insights on depression comorbidity with addictive diseases, and the impact of poly-drug exposure. A rapid analysis of exposure to drugs of abuse reveals how specific patterns of drug and poly-drug exposure are associated with increasing odds of depression. This approach detected quantitatively how different patterns of poly-drug exposure can result in increased odds of depression comorbidity, in cases diagnosed with opioid versus cocaine dependence. (Am J Addict 2017;26:632-639).

Stress-related genes and heroin addiction: A role for functional fkbp5 variants

Aims: Retention in methadone maintenance treatment (MMT) for at least one year has been associated with positive outcomes. Predictors of retention in MMT have traditionally collapsed across gender. This study hypothesizes that predictors of retention will differ between men and women, and aims to determine which factors best predict retention for each gender. Methods: Data were collected from the files of 290 patients (173 M, 117 F) admitted to MMT at an outpatient clinic in Detroit between 2002 and 2007. The modal participant was a 50-year old African American (84.8%) male (59.7%). Results: Although 35.3% of men and 44.4% of women remained in treatment for over a year, gender did not significantly predict treatment retention (X2(1) =2.47, p= .12). In the overall sample, Kendall correlations (dfs =282) revealed that presenting a urine sample positive for opiates, cocaine, or THC metabolites (rs = .29, .29, .24, respectively, all ps < .001) during the first month of treatment, having a DSM-IV diagnosis of cocaine dependence (r= .24, p<001), a non-drug Axis I diagnosis (r= .12, p= .05), or a history of emotional abuse (r= .12, p= .05) was associated with retention of less than one year. Stepwise logistic regression computed for each gender with years of opioid use entered in step 1 and the variables above entered in step 2 indicated that for males, significant predictors of retention for less than a year were: presenting a urine sample that was positive for opioids (OR=6.6) or THC metabolites (OR=4.9), having a diagnosis of cocaine dependence (OR=2.7), or a non-drug Axis I diagnosis (OR=2.1). For females, significant predictors were: presenting a urine sample positive for cocaine (OR=3.6) or THC metabolites (OR=4.9), and having a history of emotional abuse (OR=2.4). Conclusions: These findings indicate that predictors of retention in MMT differ between males and females. Future studies on MMT outcomes should consider the unique pathways by which females and males adhere to, and benefit from, MMT. Financial support: Joe Young, Sr./Helene Lycacki Funds (State of Michigan).

Predictors of retention in methadone maintenance treatment differ by gender

Aims: Retention in methadone maintenance treatment (MMT) for at least one year has been associated with positive outcomes. Predictors of retention in MMT have traditionally collapsed across gender. This study hypothesizes that predictors of retention will differ between men and women, and aims to determine which factors best predict retention for each gender. Methods: Data were collected from the files of 290 patients (173 M, 117 F) admitted to MMT at an outpatient clinic in Detroit between 2002 and 2007. The modal participant was a 50-year old African American (84.8%) male (59.7%). Results: Although 35.3% of men and 44.4% of women remained in treatment for over a year, gender did not significantly predict treatment retention (X2(1) =2.47, p= .12). In the overall sample, Kendall correlations (dfs =282) revealed that presenting a urine sample positive for opiates, cocaine, or THC metabolites (rs = .29, .29, .24, respectively, all ps < .001) during the first month of treatment, having a DSM-IV diagnosis of cocaine dependence (r= .24, p<001), a non-drug Axis I diagnosis (r= .12, p= .05), or a history of emotional abuse (r= .12, p= .05) was associated with retention of less than one year. Stepwise logistic regression computed for each gender with years of opioid use entered in step 1 and the variables above entered in step 2 indicated that for males, significant predictors of retention for less than a year were: presenting a urine sample that was positive for opioids (OR=6.6) or THC metabolites (OR=4.9), having a diagnosis of cocaine dependence (OR=2.7), or a non-drug Axis I diagnosis (OR=2.1). For females, significant predictors were: presenting a urine sample positive for cocaine (OR=3.6) or THC metabolites (OR=4.9), and having a history of emotional abuse (OR=2.4). Conclusions: These findings indicate that predictors of retention in MMT differ between males and females. Future studies on MMT outcomes should consider the unique pathways by which females and males adhere to, and benefit from, MMT. Financial support: Joe Young, Sr./Helene Lycacki Funds (State of Michigan).

Comparing the utility of homogeneous subtypes of cocaine use and related behaviors with DSM‐IV cocaine dependence as traits for genetic association analysis

Because DSM-IV cocaine dependence (CD) is heterogeneous, it is not an optimal phenotype to identify genetic variation contributing to risk for cocaine use and related behaviors (CRBs). We used a cluster analytic method to differentiate homogeneous, highly heritable subtypes of CRBs and to compare their utility with that of the DSM-IV CD as traits for genetic association analysis. Clinical features of CRBs and co-occurring disorders were obtained via a poly-diagnostic interview administered to 9,965 participants in genetic studies of substance dependence. A subsample of subjects (N = 3,443) were genotyped for 1,350 single nucleotide polymorphisms (SNPs) selected from 130 candidate genes related to addiction. Cluster analysis of clinical features of the sample yielded five subgroups, two of which were characterized by heavy cocaine use and high heritability: a heavy cocaine use, infrequent intravenous injection group and an early-onset, heavy cocaine use, high comorbidity group. The utility of these traits was compared with the CD diagnosis through association testing of 2,320 affected subjects and 480 cocaine-exposed controls. Analyses examined both single SNP (main) and SNP-SNP interaction (epistatic) effects, separately for African-Americans and European-Americans. The two derived subtypes showed more significant P values for 6 of 8 main effects and 7 of 8 epistatic effects. Variants in the CLOCK gene were significantly associated with the heavy cocaine use, infrequent intravenous injection group, but not with the DSM-IV diagnosis of CD. These results support the utility of subtypes based on CRBs to detect risk variants for cocaine addiction.

2733 – Quetiapine for the treatment of cocaine dependence

Background Cocaine abuse continues to be epidemic, and yet there are no FDA approved medications for the treatment of cocaine use disorders within the United States. Methods This 12-week, prospective, double-blind, randomized, placebo-controlled study examined the effectiveness of quetiapine (Seroquel XR TM ) versus matched placebo for the treatment of cocaine dependence in non-psychotic individuals. Sixty Individuals with a diagnosis of cocaine dependence were randomized in this study. Those who were randomized to quetiapine (N=29) were titrated up to a target dose of 400 mg/day of quetiapine, while those in the placebo arm (N=31) were given a matched placebo. All subjects had weekly clinic visits and a cognitive-behavioral therapy group session. Outcome measures included questionnaires of cocaine use, money spent on cocaine, and urine drug screens (UDS). Results The drop-out rate was substantial at 68%, however there were no group differences between the two arms of the study. Using a repeat measures ANCOVA, as a whole, the subjects in this study improved by reducing their self-reported use of cocaine (p=.018) and self reported money spent on cocaine (p=.041) over the course of the study. However, the quetiapine group was not significantly different from the placebo group. In addition, cox regression analyses yielded non-significant differences ( p = .65) between groups in predicting sobriety, as defined as three weeks negative UDS. Conclusions This study did not find group differences between the quetiapine and placebo arms, indicating that quetiapine does not appear to be beneficial in the treatment of cocaine dependence.

P01-113 - Quetiapine for the treatment of cocaine dependence

BackgroundCocaine abuse continues to be epidemic, and yet there are no FDA approved medications for the treatment of cocaine use disorders. A previous pilot study conducted by this author suggested that quetiapine may help reduce the cravings for cocaine in 22 individuals with cocaine dependence.MethodsThis 12-week, prospective, intent-to-treat, double-blind, randomized, placebo-controlled study examined the effectiveness of quetiapine (Seroquel SR™) versus matched placebo for the treatment of cocaine dependence in non-psychotic individuals. Sixty individuals with a diagnosis of cocaine dependence were randomized in this study, 29 into the quetiapine arm, and 31 into the placebo arm. Those who were randomized to quetiapine were titrated up to a target dose of 400 mg/day of quetiapine, while those on the placebo arm were given a matched placebo. All subjects had weekly clinic visits for a cognitive-behavioral therapy group session. Outcome measures included questionnaires of cocaine use, cravings for cocaine, and urine drug screen.ResultsInitial analyses indicate that the intensity, frequency, and length of cocaine cravings were reduced over 6 weeks in both the quetiapine and placebo groups. All hazard analyses indicated that the total money spent on cocaine also decreased in both groups, with a trend toward greater decrements in cocaine use the longer they remained in the study. Data analyses are ongoing to determine the potential effect of quetiapine on treatment of cocaine addiction.ConclusionsConclusions regarding the use of quetiapine as a treatment for cocaine dependence will be discussed.

Cocaine Dependence and Anxiety Sensitivity Among Patients Presenting for Residential Drug Use Treatment

Cocaine use and dependence remains an important public health concern. Thus, the identification of individual difference factors that may maintain cocaine use remains an important goal. The goal of the current study is to test whether the cognitive vulnerability of anxiety sensitivity (AS), an identified risk factor for anxiolytic use and use-related disorders, is related to cocaine dependence diagnosis (n = 168) among a sample of drug users currently enrolled in residential treatment (N = 304). Results demonstrated that AS was significantly related to cocaine dependence and remained significant after controlling for sex, age, alcohol dependence, hallucinogen dependence, major depressive disorder, panic disorder, and posttraumatic stress disorder. Taken together, these data suggest that AS may have a specific relation to cocaine dependence, calling into question the notion that AS is positively related only to drugs with anxiolytic properties.

Pretreatment Characteristics as Predictors of Retention in Cocaine-dependent Outpatients

Objective One of the principal problems traditionally found by clinicians in drug-dependence treatment programs has been the high rate of dropout. This study presents a mathematical model that predicts, through the assignment of probabilities, treatment retention in a sample of cocaine addicts. Methods The model was defined through a logistic regression analysis. Participants were 70 in number with a cocaine-dependence diagnosis, treated at a public outpatient unit in the city of Valencia (Spain). Patients were assessed at the beginning and end of the treatment period (6 mo). Results Retention rate was 50%. The results showed that the variables best predicting treatment retention were years of education and family and social situation (sociocultural context conditions). Conclusions Therefore, we suggest the application of programs, which assess patient needs and include specific intervention strategies in the areas of education and family and vocational counseling.

Modafinil for the treatment of cocaine dependence

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

Promoting abstinence from cocaine and heroin with a methadone dose increase and a novel contingency

To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 × 3 (dose × contingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100 mg/day, double-blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or “split”). The “split” contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was “split” between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The split 100 mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required.