N-Acetyl Cysteine plus Behavioral Therapy for Nicotine Dependent Pathological Gam

描述(由申请人提供)：本申请涉及广泛的挑战领域(01)行为、行为改变和预防，以及具体的挑战主题，01-DA-110：确定和/或评估可用于治疗物质使用障碍的膳食补充剂。在美国成年人中，12.8%的人报告尼古丁依赖，尼古丁依赖与各种DSM-IV轴I和II障碍高度相关。病理性赌博是一种严重的公共卫生问题，对个人和家庭都有不利影响，估计每年因失业、债务、破产和监禁而给社会造成的成本高达50亿美元，与尼古丁依赖的比例增加(41%-55%)有关，病理性赌徒的临床样本中吸烟与赌博严重程度增加和更频繁的精神问题有关。此外，研究表明，在接受行为治疗的病态赌徒中，持续使用尼古丁与更高的复发率有关。尽管人们越来越多地认识到尼古丁依赖与PG之间的关系，以及尼古丁依赖对赌博严重性的可能影响，但先前还没有研究集中于尼古丁依赖的评估和治疗如何有助于PG的成功治疗或戒烟。初步研究表明，使用想象脱敏和动机访谈(IDMI)的行为疗法在减轻PG症状方面显示出了良好的前景。尽管PG和尼古丁依赖的治疗有效，但复发在尼古丁依赖和PG患者中很常见。临床前研究表明，伏隔核内的谷氨酸水平介导了寻求奖励的行为，并可能是成瘾复发的基础。N-乙酰半胱氨酸是一种膳食补充剂、氨基酸和半胱氨酸前体药物，似乎可以调节伏隔核内的谷氨酸，并在减少可卡因依赖个人和病态赌徒的追逐奖励行为方面显示出好处。如果成功治疗尼古丁依赖型病态赌徒，N-乙酰半胱氨酸可能成为接受行为治疗的尼古丁依赖型病态赌徒的一种可行、低成本和容易获得的治疗选择。因此，我们建议研究与行为疗法结合使用的膳食补充剂N-乙酰半胱氨酸如何影响尼古丁依赖型病态赌徒的吸烟和赌博冲动以及吸烟和赌博行为。因此，我们建议对80名尼古丁依赖的病态赌徒进行N-乙酰半胱氨酸或安慰剂的随机安慰剂对照试验，他们都将接受尼古丁戒烟的简短标准化戒烟治疗(询问、建议和参考模型)，以及针对PG的6次IDMI治疗。我们假设，N-乙酰半胱氨酸加行为疗法将在急性治疗阶段导致尼古丁依赖和PG症状的更大程度的减少，并将加强更大的长期戒断。我们的研究将有助于更好地理解尼古丁依赖病态赌徒的治疗方法，以及更好地理解共生成瘾的治疗方法。如果我们的干预成功，它将有可能为尼古丁依赖同时发生的一系列精神障碍设定一个新的护理标准。RC1赠款相关性声明尼古丁依赖和病态赌博在全国多个社区的广泛个人中都有过，并与巨大的社会成本有关。这项研究建议研究饮食补充剂N-乙酰半胱氨酸与简单的行为疗法结合使用将如何影响吸烟和赌博行为。由于这项研究将集中在非物质滥用治疗环境中进行治疗，从而为那些本来可能得不到帮助的人提供治疗，因此正在测试的干预措施有可能对公共卫生产生重大影响。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (01) Behavior, Behavioral Change and Prevention and specific Challenge Topic, 01-DA-110: Identify and/or evaluate dietary supplements that could be used in treating substance use disorders. Among US adults, 12.8% report nicotine dependence, and nicotine dependence is highly associated with a variety of DSM-IV Axis I and II disorders. Pathological gambling (PG), a serious public health problem with detrimental effects on individuals and families, and with an estimated yearly cost to society of 5 billion dollars due to lost jobs, debt, bankruptcy, and incarcerations, is associated with elevated proportions of nicotine dependence (41% - 55%), and tobacco smoking in clinical samples of pathological gamblers has been associated with increased gambling severity and more frequent psychiatric problems. In addition, research suggests that continued nicotine use is associated with greater rates of relapse among pathological gamblers who received behavioral therapy. Despite increased awareness of the relationship between nicotine dependence and PG, and the possible effects of nicotine dependence on gambling severity, no previous research has focused on how assessment and treatment of nicotine dependence may aid in the successful treatment of PG or smoking cessation. Preliminary research suggests that behavioral therapy using imaginal desensitization and motivational interviewing (IDMI) has shown promise in reducing the symptoms of PG. Despite the efficacy of treatments for PG and nicotine dependence, relapse is common among individuals with nicotine dependence and PG. Preclinical studies have suggested that levels of glutamate within the nucleus accumbens mediate reward-seeking behavior and may underlie relapse seen in addictions. N-acetyl cysteine, a dietary supplement, amino acid and cysteine pro-drug, appears to modulate glutamate within the nucleus accumbens and has shown benefit in reducing the reward-seeking behavior in individuals with cocaine dependence and in pathological gamblers. If successful in treating nicotine dependent pathological gamblers, N-acetyl cysteine may serve as a viable, low-cost, and easily available treatment option for nicotine dependent pathological gamblers who receive behavioral therapy. We therefore propose to examine how a dietary supplement, N-acetyl cysteine, used in combination with behavioral therapy will affect both the urge to smoke and gamble in nicotine dependent pathological gamblers and smoking and gambling behaviors. We therefore propose a randomized placebo-controlled trial of N-acetyl cysteine or placebo with 80 nicotine dependent pathological gamblers who will all receive brief standardized smoking cessation treatment (Ask, Advise, and Refer model) for nicotine cessation and 6 sessions of IDMI for PG. We hypothesize that N-acetyl cysteine plus behavioral therapy will result in greater reduction in both nicotine dependence and PG symptoms during the acute treatment phase and will enhance greater long-term abstinence. Our research will contribute to an improved understanding of the treatment of nicotine-dependent pathological gamblers as well as a greater understanding of the treatment of co-occurring addictions. If our intervention is successful, it will have the potential to set a new standard of care for a range of psychiatric disorders that co-occur with nicotine dependence. RC1 Grant Relevance Statement Nicotine dependence and pathological gambling are experienced by a broad range of individuals in multiple communities throughout the country and are associated with substantial societal costs. This study proposes to examine how a dietary supplement, N-acetyl cysteine, used in combination with brief behavioral therapy will affect both smoking and gambling behaviors. Because the study will focus treatment in non-substance abuse treatment settings and thereby offer treatment to those who may not otherwise be helped, the interventions being tested have the potential to make a substantial public health impact.