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Purpose: Alcohol dependence, frequently seen in medical settings, is a major problem that affects the health and well-being of many individuals and their families. The purpose of this study was to examine the relationship between treatment outcomes and patient and clinician factors specifically associated with a medically oriented intervention given for the treatment of alcohol dependence. The intervention was developed for the National Institute on Alcohol Abuse and Alcoholism-sponsored COMBINE Study, a randomized controlled trial combining 2 medications, naltrexone and acamprosate, with Medical Management, with or without specialty alcohol treatment.Methods: We examined the effect of patient adherence to treatment (number of Medical Management visits, total minutes in treatment, alliance or therapeutic relationship with the clinician, patient satisfaction with treatment, and clinician adherence to the Medical Management protocol) on abstinence from alcohol, amount of heavy drinking, and clinical improvement during treatment.Results: More Medical Management visits attended and less total time spent in Medical Management treatment was associated with more days of abstinence from alcohol, reductions in heavy alcohol drinking, and a higher likelihood of clinical improvement. The patients' positive perceptions of their alliance with their clinician and their satisfaction with treatment was significantly associated with more days of abstinence from alcohol during treatment. Two clinician factors clinician confidence in the Medical Management treatment and flexibility in delivering Medical Management were also associated with better patient outcomes.Conclusions: Medically trained clinicians with minimal specialty training in alcohol dependence treatments were able to deliver a brief and effective medication management intervention that was designed to be consistent with primary care practice. [ABSTRACT FROM AUTHOR]

The risk for drug addiction is partially heritable. Genes of the dopamine system are likely candidates to harbour risk variants, as dopamine neurotransmission is involved in mediating the rewarding effects of drugs of abuse. One functional single nucleotide polymorphism in dopamine receptor D2 (DRD2), rs1076560, is involved in regulating splicing of the gene and alters the ratio of DRD2 isoforms located pre- and postsynaptically. rs1076560 has been previously associated with cocaine abuse and we set out to confirm this association in a sample of European American (EA) (n = 336) and African American (AA) (n = 1034) cocaine addicts and EA (n = 656) and AA (n = 668) controls. We also analysed the role of rs1076560 in opioid dependence by genotyping EA (n = 1041) and AA (n = 284) opioid addicts. rs1076560 was found to be nominally associated with opioid dependence in EAs (p = 0.02, OR = 1.27) and AAs (p = 0.03, OR = 1.43). When both opioid-addicted ancestral samples were combined, rs1076560 was significantly associated with increased risk for drug dependence (p = 0.0038, OR = 1.29). This association remained significant after correction for multiple testing. No association was found with cocaine dependence. These data demonstrate the importance of dopamine gene variants in the risk for opioid dependence and highlight a functional polymorphism that warrants further study., (© 2013 John Wiley & Sons Ltd/University College London.)

Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females., (© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

Dopaminergic brain systems have been documented to have a major role in drug reward, thus making genes involved in these circuits plausible candidates for susceptibility to substance use disorders. The catechol-O-methyltransferase (COMT) is involved in the degradation of catecholamines and a functional polymorphism (Val158Met) has been suggested to influence enzyme activity. In this study we hypothesize that genetic variation in the COMT gene contributes to increased risk for cocaine dependence. Cocaine-dependent individuals (n=330) and screened unaffected normal controls (n=255) were genotyped for three SNPs in the COMT gene (rs737865, rs4680 (Val158Met), rs165599). All cases and controls were of African descent. Genotype and allele frequencies differed significantly for the Val158Met polymorphism between cases (f(Met)=35%) and controls (f(Met)=27%) (p=0.004; corrected p=0.014; OR 1.44; 95% CI 1.12-1.86). Haplotype analysis showed a significant association for a two-marker haplotype rs737865-Val158Met (p=0.005). Results suggest that variation in COMT increases risk for cocaine dependence. The low enzyme activity 158Met allele or haplotypes containing this variant might have functional effects on dopamine-derived reward processes and cortical functions resulting in increased susceptibility for cocaine dependence. Additional studies are required to elucidate the role of COMT in the pathophysiology of substance use disorders.

Despite years of active research, there are still no approved medications for the treatment of cocaine dependence. Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled conditions, and the current study assessed whether modafinil would improve clinical outcome in cocaine-dependent patients receiving standardized psychosocial treatment. This was a randomized, double-blind, placebo-controlled trial conducted at a university outpatient center (from 2002 to 2003) on a consecutive sample of 62 (predominantly African American) cocaine-dependent patients (aged 25-63) free of significant medical and psychiatric conditions. After screening, eligible patients were randomized to a single morning dose of modafinil (400 mg), or matching placebo tablets, for 8 weeks while receiving manual-guided, twice-weekly cognitive behavioral therapy. The primary efficacy measure was cocaine abstinence based on urine benzoylecgonine levels. Secondary measures were craving, cocaine withdrawal, retention, and adverse events. Modafinil-treated patients provided significantly more BE-negative urine samples (p=0.03) over the 8-week trial when compared to placebos, and were more likely to achieve a protracted period (> or =3 weeks) of cocaine abstinence (p=0.05). There were no serious adverse events, and none of the patients failed to complete the study as a result of adverse events. This study provides preliminary evidence, which should be confirmed by a larger study, that modafinil improves clinical outcome when combined with psychosocial treatment for cocaine dependence.