Progesterone Treatment for Cocaine-Dependent Women

描述（由申请人提供）：可卡因依赖仍然是全国范围内的一个主要社会和医疗问题。此外，可卡因滥用是妇女中的一个严重问题，妇女占寻求治疗的可卡因滥用者的约30%。妇女比男子更快地对可卡因产生依赖，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"硬性"药物滥用的治疗。所有可卡因治疗入院的大多数（73%）是吸食可卡因，42%因吸食快克可卡因而入院的人是妇女。快克可卡因使用的增加，特别是在妇女中的增加，与性传播艾滋病毒的增加间接有关。尽管如此，尚未作出协调一致的努力，针对女性可卡因滥用者进行药物治疗。我们最近在非寻求治疗的可卡因滥用者中进行的实验室研究表明，口服微粒化孕酮降低了可卡因给药的积极主观效应，并且这些效应在女性中比在男性中更强。此外，口服微粉化孕酮实际上减弱可卡因诱导的心血管效应的增加，表明这种药物可能对可卡因毒性有保护作用。最后，初步数据表明，口服微粒化孕酮减少了女性吸食可卡因的自我管理。与合成孕激素相反，口服微粉化孕酮具有高安全性，可以长期给予女性，最常见的副作用是镇静和不规则月经出血。综上所述，这些研究结果表明，口服微粒化黄体酮可能具有临床效用，减少可卡因依赖的妇女寻求治疗可卡因的使用。该RFA的目的是支持药物滥用的试点临床试验，包括特殊人群。因此，我们建议进行一项随机安慰剂对照治疗试验，以评估口服微粒化孕酮与安慰剂相比在依赖快克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。我们将使用代金券激励诊所出勤率，以提高保留率，我们将提供简短的依从性增强治疗。这项试点治疗试验的结果将提供一个初步的基础，以决定是否进行一项大规模的临床试验，将包括一个更异质性的妇女群体（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).