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Scholarly Works (5 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2017)
Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for the treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies, and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research.
    Cover page: Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2017)

    Background and objectives

    Pharmacogenetic studies of alcohol use disorder (AUD) have suggested that the efficacy of treatments for AUD is, in part, influenced by the genetic background of an individual. Since the frequency of alleles associated with pharmacotherapy for AUD varies by ancestral background, the effectiveness of medications used to treat AUD may vary among different populations. The purpose of this review is to summarize the existing pharmacogenetic studies of treatments for AUD in individuals of European, East Asian, African, and American Indian/Alaska Native ancestry.

    Methods

    Electronic databases were searched for pharmacogenetic studies of AUD treatment that included individuals of diverse ancestral backgrounds.

    Results

    Pharmacogenetic studies of AUD reviewed here have primarily investigated genetic variation thought to play a role in the response to naltrexone, ondansetron, and topiramate. There is support that the A118G polymorphism should be further investigated in individuals of East Asian ancestry.

    Discussion and conclusions

    Given the lack of pharmacogenetic research on response to AUD medication in ethnic minority populations and the mixed results, there is a critical need for future studies among individuals of different ancestries. More efforts should be devoted to standardizing procedures such that results can be more readily integrated into a body of literature that can directly inform clinical practice.

    Scientific significance

    This review highlights the importance for future research to aim for inclusiveness in pharmacogenetic studies of AUD and increase diversity of clinical trials in order to provide the best treatment outcomes for individuals across different racial and ethnic groups. (Am J Addict 2017;26:516-525).
      Cover page: Review: Pharmacogenetics of alcoholism treatment: Implications of ethnic diversity
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2015)
      There is a high prevalence of comorbid tobacco use and alcohol use disorder (AUD), affecting more than 6 million people in the US. Globally, tobacco and alcohol use rank fourth and fifth, respectively, for disability-adjusted life-years lost. Levels of alcohol use are higher in smokers than nonsmokers, and the prevalence of smoking is higher in heavy drinkers compared with nondrinkers. This relationship is driven by many different factors, including genetics, neurobiological mechanisms, conditioning processes, and psychosocial influences. Although this unique population tends to experience more negative health consequences, more severe AUD, and poorer response to treatment than those with either AUD or tobacco use disorder alone, there are currently no available treatment protocols tailored to this comorbid condition. In this review, we provide a comprehensive review of ongoing clinical research into smoking cessation options for heavy-drinking smokers (HDS) through an evaluation of the effect of promising novel pharmacotherapies as well as combination therapies, including varenicline, naltrexone, the combination of varenicline and naltrexone, and the combination of naltrexone and nicotine replacement therapy (NRT). These treatments are considered in light of the standard of care for smoking cessation, and seek to improve upon the available guidelines for this sizeable subgroup of smokers, namely those smokers who drink heavily.
        Cover page: Pharmacological Options for Smoking Cessation in Heavy-Drinking Smokers
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)

        Medication development for alcoholism typically includes experimental pharmacology studies with non-treatment-seeking individuals with alcohol use disorder (AUD) paving the way for randomized controlled trials in treatment-seekers with AUD.

        The goal of this study is to provide a direct comparison between AUD treatment-seeking research participants and non-treatment-seeking participants on demographic and clinical variables and to test whether variables that differentiate the two groups are associated with clinical outcomes.

        Non-treatment-seeking AUD participants (n = 213; 76.3% male) who completed behavioral pharmacology studies were compared to treatment-seekers who completed the COMBINE Study (n = 1383; 69.1% male) on demographic and clinical variables. Analyses examined whether the variables that differentiated the two groups predicted treatment outcomes in the COMBINE Study.

        Analyses revealed that treatment-seeking participants were older, had more years of education, higher Alcohol Dependence Scale scores, higher Drinker Inventory of Consequences scores, higher Obsessive Compulsive Drinking Scale scores, a greater number of DSM-IV symptoms of AUD, longer duration of AUD, and consumed more standard drinks and more drinks per drinking day (i.e., in the past 30 days) compared to non-treatment-seeking participants. Nearly all characteristics that differed between the groups predicted at least one of the primary clinical outcomes of the COMBINE Study.

        This study highlights a host of clinical and demographic factors that differ between non-treatment-seeking and treatment-seeking research participants and the clinical significance of these variables. Differences between samples should be considered and addressed in order to promote greater consilience across stages of medication development.

          Cover page: Differences between treatment-seeking and non-treatment-seeking participants in medication studies for alcoholism: do they matter?
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2016)

          There is a strong association between cigarette smoking and alcohol use at the epidemiological, behavioral, and molecular levels, and this co-use creates substantial impediments to smoking cessation among smokers who are also heavy drinkers. Compared with individuals who only smoke, those who both drink and smoke heavily experience more severe health consequences and have greater difficulty in quitting smoking. During smoking abstinence, greater alcohol use is associated with decreased odds of smoking cessation, and smokers are substantially more likely to experience a smoking lapse during drinking episodes. As heavy drinking smokers are less responsive to the currently available pharmacological treatments, this subgroup of high-risk substance users possesses a unique clinical profile and treatment needs. Thus, treatment development for heavy drinking smokers represents a significant and understudied research area within the field of smoking cessation. This review will briefly describe findings from epidemiological, behavioral, and molecular studies illustrating alcohol and tobacco co-use and identify how the behavioral and neurobiological mechanisms underlying the interaction of alcohol and nicotine may inform the development of targeted treatments for this unique population of smokers.

            Cover page: Current insights into the mechanisms and development of treatments for heavy drinking cigarette smokers.
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