Efficacy of Naltrexone in Women's Smoking Cessation

描述(由申请人提供)： 尽管女性可能特别容易受到长期吸烟的有害影响，但有证据表明，她们在维持戒烟方面可能比男性更困难。鉴于女性对尼古丁替代和其他传统治疗的反应降低，习惯性吸烟、更有针对性的药物治疗和干预策略可能是必要的，以提高她们的戒烟率。我们小组和其他人的初步数据表明，阿片类拮抗剂纳曲酮可能是女性吸烟者有效的药物治疗方法。这项拟议研究的目的是进行一项随机临床试验，比较50毫克口服纳曲酮和安慰剂与标准戒烟治疗和尼古丁贴片和咨询相结合的辅助治疗。参与者(N=324人)将在戒烟日期前一周开始接受纳曲酮或安慰剂治疗(25毫克，连续三天；此后为50毫克)，并在戒烟日期后继续服用12周。纳曲酮的效果将在戒烟前、最初戒烟、预防复发和一年的随访中进行评估。据假设，性行为将缓和纳曲酮对结局的影响，纳曲酮可以改善女性长期禁欲的戒烟率，但对男性没有影响。第二个目标将是阐明女性对纳曲酮治疗反应的潜在机制。体重(相对体重增加和体重担忧)和与吸烟相关的变量(减少吸烟的愉悦感、味觉、渴望和缓解负面戒烟情绪)可能是纳曲酮提高女性戒烟率的重要因素。还将检查服药依从性、心理社会压力和纳曲酮的代谢物6-|3-纳曲醇的水平。总之，拟议的临床试验将提供一项关于纳曲酮辅助戒烟治疗的性别差异的全面研究。鉴于女性持续高吸烟率对公共健康的担忧和严重的健康后果，拟议的研究可能为针对内源性阿片系统的新治疗策略提供重要信息，以选择性地帮助女性戒烟。

DESCRIPTION (provided by applicant): Although women may be particularly susceptible to the damaging effects of chronic cigarette smoking, evidence indicates that they may have more difficulty in maintaining smoking cessation than men. Given women's reduced response to nicotine replacement and other traditional treatments, habitual cigarette smoking, more targeted pharmacotherapy and intervention strategies may be necessary to improve their quit rates. Preliminary data by our group and others indicate that the opioid antagonist naltrexone may be an effective pharmacotherapy approach for female smokers. The purpose of the proposed study is to conduct a randomized clinical trial to compare adjunct treatment with 50 mg oral naltrexone vs. placebo in conjunction with standard smoking cessation treatment with nicotine patch and counseling. Participants (N=324) will be randomized to receive either naltrexone or placebo starting one week prior to the quit date (25 mg for three days; 50 mg thereafter) and continue for 12 weeks after the quit date. The effects of naltrexone will be evaluated during the pre-quit date period, initial smoking cessation, relapse prevention, and at one-year follow-up. It is hypothesized that sex will moderate the effects of naltrexone on outcome, with naltrexone improving prolonged abstinence quit rates in women but not in men. The secondary goal will be to elucidate the mechanisms underlying women's treatment response to naltrexone. Weight (relative weight gain and weight concerns) and smoking-related variables (reduced cigarette pleasure, taste, craving and relief of negative withdrawal affect) may be important factors by which naltrexone improves quit rates in women. Medication compliance, psychosocial stress and levels of naltrexone's metabolite, 6-|3-naltrexol, will also be examined. In sum, the proposed clinical trial will provide a comprehensive study of sex differences in response to adjunct treatment with naltrexone for smoking cessation. Given the public health concerns and significant health consequences of women's continued high rates of smoking, the proposed study may provide important information on a novel treatment strategy targeting the endogenous opioid system to selectively aid in women's smoking cessation.