We investigated whether measures of impulsivity, aggression and sensation seeking differed between cocaine-dependent subjects and controls, and whether these measures were related to treatment-outcome for cocaine patients. Pre-treatment assessments of impulsivity (Barratt Impulsivity Scale [BIS]), aggression (Buss-Durkee Hostility Inventory [BDHI]) and sensation seeking (Zuckerman Sensation Seeking Scale [SSS]) were obtained for 141 African-American cocaine-dependent patients entering a 12-week, intensive outpatient treatment program and 60 controls. The outcome measures were number of negative urine drug screens, days in treatment, dropout rates and number of treatment sessions. Cocaine patients reported significantly higher scores on the SSS, the BIS and the BDHI than controls. Furthermore, the SSS scores showed a significantly negative correlation with days in treatment and negative urines, and a significant positive correlation with the dropout rate. The BIS and the BDHI scores were significantly associated with days in treatment and dropout rates respectively. A combination of the three variables contributed significantly toward predicting retention and abstinence. Higher levels of pretreatment impulsivity and aggression and sensation seeking seem to associated with poor treatment outcome for cocaine dependent patients receiving intensive outpatient treatment. Combining these behavioral measures with other clinical predictors may help in early identification of 'poor responders' who may benefit from additional or alternative treatment approaches.

Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans.

Two polymorphisms of the human mu opioid receptor gene are described. A non-coding region polymorphism (G to T) occurs at nucleotide 175 preceding the initiation of translation. A coding polymorphism in exon 1 (C to T) at nucleotide 229 changes an alanine residue to a valine residue. Frequencies of these polymorphisms were examined in groups of cocaine and/or opioid dependent individuals and matched controls. There were no significant differences between groups, although a trend (p= 0.05) towards a higher frequency of the 229 valine allele was observed in the substance abuse group, suggesting a need for large, well-controlled studies of this polymorphism in severe substance abusers.

Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent results. Very low dose naltrexone (VLNTX) was recently found to reduce opioid tolerance and dependence in animal and clinical studies. We decided to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing withdrawal during detoxification. In a multi-center, double-blind, randomized study at community treatment programs, where most detoxifications are performed, 174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily for 6 days, together with methadone in tapering doses. VLNTX-treated individuals reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at discharge and were not accompanied by a significantly higher retention rate. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Further studies should explore the use of VLNTX, combined with full and partial opioid agonist medications, in detoxification and longterm treatment of opioid dependence.

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