Progesterone Treatment for Cocaine-Dependent Women

描述(申请人提供)：可卡因依赖仍然是全国范围内的一个主要的社会和医疗问题。此外，可卡因滥用是妇女中的一个严重问题，在寻求治疗的可卡因滥用者中，妇女约占30%。女性对可卡因的依赖比男性更快，女性吸毒者比男性吸毒者更有可能接受可卡因和海洛因等“硬”滥用药物的治疗。大多数(73%)的可卡因治疗入院是因为吸食可卡因，42%的吸食强效可卡因的人是女性。这种强效可卡因使用的增加，特别是在女性中，间接地与性传播艾滋病毒的增加有关。尽管如此，在针对女性可卡因滥用者的药物治疗方面，还没有做出协调一致的努力。我们最近对未接受治疗的可卡因滥用者进行的实验室研究表明，口服微粒化黄体酮减少了服用可卡因的积极主观影响，这些影响在女性身上比在男性身上更强烈。此外，口服微粒化黄体酮实际上可以减轻可卡因引起的心血管效应的增加，这表明这种药物可能对可卡因毒性具有保护作用。最后，初步数据表明，口服微粒化黄体酮可以减少女性吸食可卡因的次数。与合成孕酮相反，口服微粉化黄体酮具有很高的安全性，可以长期给妇女服用，最常见的副作用是镇静和经期不规则出血。综上所述，这些发现表明，口服微粒化黄体酮可能在寻求治疗的可卡因依赖女性减少可卡因使用方面具有临床实用价值。该RFA的目标是支持药物滥用药物的试点临床试验，包括特殊人群。因此，我们建议进行一项随机的安慰剂对照治疗试验，以评估口服微粒化黄体酮与安慰剂在依赖强效可卡因的女性中的疗效。药物滥用者药物治疗试验中最大的问题之一是依从性和保留性差。我们将使用就诊代金券激励措施来提高保留率，我们将提供简短的遵从性增强疗法。这一试验性治疗试验的结果将为决定是否进行一项大规模临床试验提供初步依据，该试验将包括一组更加多样化的妇女(即主要通过吸烟以外的其他途径使用可卡因的妇女)。

DESCRIPTION (provided by applicant): Cocaine dependence continues to be a major social and medical problem nationwide. Moreover, cocaine abuse is a substantial problem among women, with women making up approximately 30% of cocaine abusers seeking treatment. Women become dependent on cocaine more rapidly than men do, and female drug users are more likely than male drug users to be in treatment for "hard" drugs of abuse, such as cocaine and heroin. The majority (73%) of all cocaine treatment admissions are for smoked cocaine and 42% of individuals admitted for smoking crack cocaine were women. This increase in crack cocaine use, particularly among women, has indirectly been associated with an increase in sexually transmitted HIV. Despite this, no concerted efforts have been made to target a pharmacological treatment for female cocaine abusers. Our recent laboratory studies in non-treatment seeking cocaine abusers have shown that oral micronized progesterone reduces the positive subjective effects of cocaine administration and these effects are more robust in females than in males. Further, oral micronized progesterone actually attenuates cocaine-induced increases in cardiovascular effects indicating that this medication may be protective against cocaine toxicity. Lastly, preliminary data indicate that oral micronized progesterone decreases smoked cocaine self- administration in females. Oral micronized progesterone, as opposed to synthetic progestins, has a high safety profile and can be administered to women for prolonged periods, with the most common side effects being sedation and irregular menstrual bleeding. Taken together, these findings suggest that oral micronized progesterone may have clinical utility in reducing cocaine use in cocaine-dependent women seeking treatment. The objective of this RFA is to support pilot clinical trials of medications for substance abuse, including special populations. As such, we propose to conduct a randomized placebo-controlled treatment trial to evaluate the efficacy of oral micronized progesterone compared to placebo in women dependent on crack cocaine. One of the biggest problems in pharmacological treatment trials with substance abusers is poor compliance and retention. We will use voucher incentives for clinic attendance to enhance retention and we will provide brief compliance enhancement therapy. The results of this pilot treatment trial will provide a preliminary basis on which to decide whether to undertake a large-scale clinical trial that would include a more heterogeneous group of women (i.e., women who primarily use cocaine by other routes other than smoked).