Effect of Baclofen on Alcohol Cue-Elicited Urges to Drink and Smoke

巴氯芬对酒精提示引起的饮酒和吸烟冲动的影响

• 批准号: 8063250
• 负责人: Lorenzo Leggio
• 金额: $ 4.05万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-25 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063250
• 关键词: Abstinence; Accounting; Affect; Agonist; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholic Beverages; Alcoholism; Alcohols; Applications Grants; Attention; Baclofen; Behavioral; Biological; Blood Pressure; Cause of Death; Cessation of life; Cigarette; Cirrhosis; Clinical; Clinical Trials; Comorbidity; Consumption; Controlled Study; Cues; DSM-IV; Dependency; Diagnosis; Double-Blind Method; Drug abuse; Drug effect disorder; Exposure to; Foundations; Funding; Funding Agency; Goals; Grant; Heart Rate; Heavy Drinking; Human; Individual; Intake; Intervention; Knowledge; Laboratories; Lead; Light; Measures; Morbidity - disease rate; Neurobiology; Nicotine; Nicotine Dependence; Outcome; Parents; Participant; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Population; Psychophysiology; Public Health; Questionnaires; Randomized; Research; Research Personnel; Risk; Role; Smell Perception; Smoke; Smoker; Smoking; Staging; Surveys; Testing; Tobacco; United States National Institutes of Health; Vision; Withholding Treatment; Woman; addiction; alcohol abstinence; alcohol craving; alcohol cue; alcohol relapse; alcohol research; alcohol response; alcohol use disorder; base; biobehavior; comparative efficacy; control trial; craving; cue reactivity; double-blind placebo controlled trial; drinking; men; mortality; non-alcoholic; novel strategies; open label; pressure; problem drinker; programs; public health relevance; receptor; reduced alcohol use; research study; response; saliva secretion; smoking cessation

DESCRIPTION (provided by applicant): There is a high co-morbidity between alcohol and nicotine dependence. Alcohol-dependent smokers show an increased risk of tobacco-related mortality and morbidity, and smoking-related illnesses are the leading cause of death among alcoholics. Therefore, there is a crucial need to consider smoking when we treat alcoholics. Currently, there are no approved medications able to reduce both alcohol drinking and smoking in individuals with alcohol and nicotine co-dependencies. Therefore, there is a critical need in the field to identify medications that may be effective in treating both dependencies. Recent research evidence suggests the involvement of the GABAB receptor in the neurobiology of addictions. Human studies have shown that the selective GABAB receptor agonist baclofen reduces alcohol craving and intake. Interestingly, baclofen showed efficacy and a safe profile even when administered to a severely ill population - alcohol dependent patients with cirrhosis. Moreover, a recent double-blind placebo- controlled trial in non-alcoholics also indicated that baclofen reduced the number of cigarettes smoked per day and cigarette craving, suggesting the utility of baclofen in smoking cessation. These results lead one to conclude that baclofen has the potential to be a new pharmacotherapy intervention for the treatment of alcohol dependent patients who smoke, though this aspect has never been formally investigated. Based on this background, Dr. Leggio received a grant from the 'ABMRF/The Foundation for Alcohol Research' to perform a 12-week double-blind, placebo-controlled between-subject treatment study to investigate the dual roles of baclofen (80mg/d) in reducing alcohol and cigarette consumption in alcohol- dependent, heavy-drinking individuals who also satisfy DSM-IV criteria for current nicotine dependence. The primary aims of that study are to investigate whether baclofen, as compared to placebo, reduces the percentage of heavy drinking days and increases alcohol abstinence (cumulative alcohol abstinence duration); and whether baclofen, as compared to placebo, reduces the number of cigarettes per day and increases smoking abstinence (cumulative smoking abstinence duration). The present proposal is consistent with the goals of the present RFA SOAR-R03 to supplement new investigators/early stage investigators who have a commitment of support to conduct research in clinical alcohol research from funding sources other than NIH (e.g. private foundation). The present R03 SOAR consists of a sub-study, which will allow adding a laboratory biobehavioral component to the parent ABMRF- funded study. While the parent funded study will compare the efficacy of baclofen to placebo on alcohol and cigarette consumption during a 12-week naturalistic period, the goal of the present R03 SOAR is to provide information on the biobehavioral mechanisms of how baclofen affects urges to drink and smoke after exposure to nonalcoholic (neutral) vs. alcoholic cues. Specifically, this R03 SOAR sub-study project will be a 1-day double-blind, placebo-controlled, between-subject randomized cue-reactivity (CR) experiment with baclofen (80mg/d) conducted in those alcohol-dependent nicotine-dependent participants of the parent study. During the experiment, urges to drink and to smoke will be assessed after exposure to nonalcoholic and alcoholic cues. Attention to the sight and smell of cues and psychophysiological responses (heart rate, mean arterial pressure and salivation changes) will also be assessed during the CR experiment. The overall goal of this experiment is to explore the biobehavioral mechanisms how baclofen affects urges to drink and smoke after the exposure to alcoholic cues. PUBLIC HEALTH RELEVANCE: Alcohol use disorders account for 100,000 excess deaths per year. Alcohol-dependent smokers show an increased risk of tobacco-related mortality and morbidity, and smoking-related illnesses represent the leading cause of death among alcoholics. Interventions that reduce both alcohol and nicotine dependence may have important public health implications. The goal of this research is to explore the biobehavioral mechanisms of how baclofen affects urges to drink and smoke in alcoholic smokers. This gain in knowledge may lead to more effective pharmacological treatments for alcoholic smokers.

描述（由申请人提供）：酒精和尼古丁依赖性之间存在很高的合并症。依赖酒精的吸烟者表现出与烟草相关死亡率和发病率的风险增加，与吸烟有关的疾病是酗酒者死亡的主要原因。因此，当我们治疗酗酒者时，至关重要的是考虑吸烟。目前，尚无批准的药物可以减少酒精和尼古丁共同依赖性的人的饮酒和吸烟。因此，该领域的急需需要确定可能有效治疗这两种依赖性的药物。 最近的研究证据表明，GABAB受体参与成瘾神经生物学。人类的研究表明，选择性GABAB受体激动剂巴氯芬降低了酒精的渴望和摄入量。有趣的是，即使对严重疾病的人群给予肝硬化患者，巴氯芬即使给予严重疾病的人群也会显示出疗效和安全的特征。此外，最近在非酒精饮料中进行的双盲安慰剂对照试验还表明，巴氯芬减少了每天吸烟的香烟数量和渴望的香烟，这表明巴氯芬在戒烟方面的效用。这些结果导致人们得出结论，巴氯芬有可能成为一种新的药物治疗干预措施，以治疗吸烟的依赖酒精的患者，尽管这一方面从未得到正式研究。 Based on this background, Dr. Leggio received a grant from the 'ABMRF/The Foundation for Alcohol Research' to perform a 12-week double-blind, placebo-controlled between-subject treatment study to investigate the dual roles of baclofen (80mg/d) in reducing alcohol and cigarette consumption in alcohol- dependent, heavy-drinking individuals who also satisfy DSM-IV criteria for current nicotine dependence.该研究的主要目的是研究巴氯芬与安慰剂相比是否减少了饮酒日的百分比并增加了酒精戒酒（累积酒精戒酒持续时间）；与安慰剂相比，巴氯芬是否可以减少每天的香烟数量并增加戒烟（累积的吸烟戒酒持续时间）。 本提案与当前RFA SOAR-R03的目标一致，以补充新的研究人员/早期研究人员，他们承诺支持NIH以外的其他资金来源（例如私人基金会）进行临床酒精研究研究。目前的R03 SOAR由一个子研究组成，这将允许将实验室生物行为成分添加到父母ABMRF资助的研究中。虽然父母资助的研究将比较巴氯芬对安慰剂在12周的自然主义时期对酒精和香烟消费的功效，但目前的R03 SOAR的目标是提供有关巴氯芬的生物行为机制的信息，baclofen如何影响不含酒精（中性）vs. vs. vs. vs. vs. vs. vs. vs. vs. cues。具体而言，该R03 SOAR子研究项目将是一个为期1天的双盲，安慰剂对照，受试者之间的随机提示反应性（CR）实验，该实验是在父母研究的那些依赖酒精依赖性的尼古丁参与者中进行的Baclofen（80mg/d）。在实验期间，在暴露于非酒精和酒精提示后，将评估喝酒和吸烟的冲动。在CR实验期间，还将评估注意线索和心理生理反应的视力和气味（心率，平均动脉压和唾液变化）。该实验的总体目的是探索生物行为机制，即巴氯芬如何影响暴露于酒精提示后喝酒和吸烟的冲动。 公共卫生相关性：酒精使用障碍每年造成100,000例过剩死亡。依赖酒精的吸烟者表现出与烟草有关的死亡率和发病率的风险增加，与吸烟有关的疾病代表了酗酒者死亡的主要原因。减少酒精和尼古丁依赖性的干预措施可能具有重要的公共卫生影响。这项研究的目的是探索巴氯芬如何影响酗酒者饮用和吸烟的生物行为机制。知识的增长可能会导致对酒精吸烟者的更有效的药理治疗。