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Context: Cocaine dependence (CD) and related behaviors are highly heritable, but no genetic association has been consistently demonstrated. A recent genome-wide study of drug dependence identified an association between cocaine-induced paranoia (CIP) and a single-nucleotide polymorphism (SNP) in the alpha-endomannosidase (MANEA) locus in a family-based sample of European Americans and African Americans., Objective: To conduct a comprehensive genetic association study of the MANEA locus with CD and CIP., Design: Genome-wide association study., Setting: Four university hospitals., Participants: A total of 3992 individuals from 2 family-based and 2 case-control samples., Intervention: Participants were classified as having CD or CIP or as a control using the Semi-Structured Assessment for Drug Dependence and Alcoholism. They were genotyped for 11 SNPs spanning MANEA and its surrounding region., Main Outcome Measure: Association of CD and CIP with individual SNPs and haplotypes., Results: Cocaine-induced paranoia was associated with 6 SNPs in the European American families and 9 SNPs in the African American families. The strongest evidence in the total sample of families was observed in 3 markers located in the promoter and 3' untranslated regions (P < .001). The association of MANEA SNPs with CD in both family samples was much weaker. In the African American case-control sample, multiple markers were significantly associated with CIP and CD; CIP and CD were also significantly associated with a 2-SNP haplotype in the European American case-control sample. The A allele of the 3' untranslated region SNP rs9387522 was associated with increased risk of CIP in all 4 data sets., Conclusions: Our findings suggest that CD and associated behaviors may involve biological pathways not typically thought to be associated with brain metabolism.

Background: Studies of remission from drug dependence have most often been based on treatment samples, with limited generalizability to persons who may benefit from but never seek substance abuse treatment. Little is known about remission patterns among drug users in the community., Objective: To identify patterns and predictors of remission in a community sample of drug users followed up prospectively., Design: Three waves of data on a range of individual and interpersonal correlates of drug abuse and health care service use were collected between April 1997 and October 2000., Setting: Areas of metropolitan San Juan where drug sales were known to occur., Participants: Two hundred seventy-five women aged 18 to 35 who were crack cocaine or injecting drug users., Main Outcome Measures: Self-reported drug use validated with urine screens and drug use dependence criteria based on the DSM-IV., Results: Most (86.9%) of the women were drug dependent at baseline. By wave 3, fewer than half (42.6%) of the women were dependent, 13.8% had subthreshold disorder, and 17.8% used substances but did not endorse any dependence criteria. Cessation of use and decreases in the number of dependence criteria endorsed were significantly less likely for women with depressive symptoms (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.88-0.96; and OR, 0.88; 95% CI, 0.86-0.90; respectively), with a partner who engaged in criminal activities (OR, 0.30; 95% CI, 0.16-0.58; and OR, 0.63; 95% CI, 0.46-0.85; respectively), and who traded sex for money or drugs (OR, 0.12; 95% CI, 0.05-0.29; and OR, 0.26; 95% CI, 0.19-0.35; respectively)., Conclusions: Drug use patterns and rates of dependence fluctuated substantially over time among drug users recruited from the community. Findings regarding the characteristics that impede remission suggest that mental health practitioners have an important role to play in community-based outreach and interventions designed to support women's efforts to stop using drugs.

Background: Previous studies document neuropsychological deficits associated with stimulant abuse, but findings are inconsistent., Methods: We identified 50 twin pairs in which only 1 member had heavy stimulant abuse (cocaine and/or amphetamines) ending at least 1 year before the evaluation. The co-twin control research design controls for familial vulnerability and makes it easier to identify neuropsychological deficits that are consequences of stimulant abuse. Subjects were administered an extensive neuropsychological test battery organized into the following 5 functions: attention, executive functioning, motor skills, intelligence, and memory., Results: Multivariate tests showed that abusers performed significantly worse than nonabusers on functions of attention and motor skills. Within each of these functions, univariate tests showed that abusers performed significantly worse on certain tests of motor skills and attention. In contrast, abusers performed significantly better on one test of attention measuring visual vigilance. Within the abuser group, higher levels of stimulant use were largely uncorrelated with neuropsychological test scores, although a few significant correlations indicated better functioning with more stimulant use., Conclusions: With ideal controls, this study demonstrates that deficits in attention and motor skills persist after 1 year of abstinence from stimulant use and raises hypotheses regarding relative strengths on a vigilance task among abusers.

Background: Long-term (5-year) outcomes of community treatment for cocaine dependence were examined in relation to problem severity at treatment entry and treatment exposure throughout the follow-up period., Methods: Interviews were conducted at 1 and 5 years after treatment for 708 subjects (from 45 programs in 8 cities) who met DSM-III-R criteria for cocaine dependence when admitted to treatment in 1991-1993. Primary outcome measures included cocaine use and arrests. Self-reported cocaine use showed high overall agreement with urine (79% agreement) and hair (80% agreement) toxicology analyses., Results: Weekly cocaine use was reported by 25% of the sample at 5 years, slightly higher than the 21% at 1 year. Similarly, 26% had cocaine detected in urine specimens at follow-up and 18% reported having been arrested. Poorer long-term outcomes were related to higher problem severity at treatment admission and low treatment exposure., Conclusions: The large decreases in cocaine use 1 year after treatment discharge were sustained during the 5-year follow-up. Severity of drug and psychosocial problems at intake was predictive of long-term outcomes and outcomes improved in direct relation to level of treatment exposure.

Background: This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients., Methods: Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month., Results: Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed., Conclusion: Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.

Background: This national study focused on posttreatment outcomes of community treatments of cocaine dependence. Relapse to weekly (or more frequent) cocaine use in the first year after discharge from 3 major treatment modalities was examined in relation to patient problem severity at admission to the treatment program and length of stay., Methods: We studied 1605 cocaine-dependent patients from 11 cities located throughout the United States using a naturalistic, nonexperimental evaluation design. They were sequentially admitted from November 1991 to December 1993 to 55 community-based treatment programs in the national Drug Abuse Treatment Outcome Studies. Included were 542 patients admitted to 19 long-term residential programs, 458 patients admitted to 24 outpatient drug-free programs, and 605 patients admitted to 12 short-term inpatient programs., Results: Of 1605 patients, 377 (23.5%) reported weekly cocaine use in the year following treatment (dropping from 73.1% in the year before admission). An additional 18.0% had returned to another drug treatment program. Higher severity of patient problems at program intake and shorter stays in treatment (<90 days) were related to higher cocaine relapse rates., Conclusions: Patients with the most severe problems were more likely to enter long-term residential programs, and better outcomes were reported by those treated 90 days or longer. Dimensions of psychosocial problem severity and length of stay are, therefore, important considerations in the treatment of cocaine dependence. Cocaine relapse rates for patients with few problems at program intake were most favorable across all treatment conditions, but better outcomes for patients with medium- to high-level problems were dependent on longer treatment stays.

Background: We determined the nature and recovery of procedural and declarative memory functioning in a cocaine-abusing cohort in the 45-day period following use., Methods: Thirty-seven cocaine abusers and 27 control subjects were administered the following memory and mood measures: California Verbal Learning Test, recall of the Rey-Osterrieth Complex Figure Test, Pursuit Rotor Task, and Profile of Mood States at 4 visits (within 72 hours of admission and at 10, 21, and 45 days following abstinence)., Results: Analysis of performance on the Rey-Osterrieth Complex Figure Test revealed that both groups improved in their recall over repeated administrations, though the control group recalled significantly more of the information than cocaine subjects during the 45-day interval. Results for the California Verbal Learning Test indicated improved learning for both subject groups over time, but no group x time interaction. On the Pursuit Rotor Task, cocaine abusers improved their performance at a faster rate than controls at visit 1. At day 45 (visit 4), cocaine abusers again showed improvement on the Pursuit Rotor Task, whereas controls demonstrated a relative plateau in rate of learning., Conclusions: This study documented a lasting detrimental effect on a sensitive nonverbal declarative memory task in cocaine-dependent subjects following abstinence of 45 days. In contrast, abstinence from cocaine during this 45-day period was associated with sustained improvement on a motor learning test in the cocaine abusers relative to controls.