Progesterone Treatment for Cocaine-Dependent Women

描述（由申请人提供）：可卡因依赖仍然是全国一个主要的社会和医疗问题。此外，可卡因滥用在妇女中是一个严重问题，在寻求治疗的可卡因滥用者中，妇女约占30%。妇女比男子更容易对可卡因产生依赖，而女性吸毒者比男性吸毒者更有可能因可卡因和海洛因等“硬性”滥用药物而接受治疗。在所有接受可卡因治疗的患者中，大多数（73%）是因吸食可卡因而入院的，42%因吸食快克可卡因而入院的患者是女性。快克可卡因使用量的增加，特别是在妇女中，与性传播艾滋病毒的增加间接相关。尽管如此，尚未作出协调一致的努力，以针对女性可卡因滥用者的药物治疗为目标。我们最近对不寻求治疗的可卡因滥用者进行的实验室研究表明，口服微孕酮会降低可卡因给药的积极主观效应，而且这些效应在女性中比在男性中更为明显。此外，口服微量孕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有保护作用。最后，初步数据表明，口服微孕酮可减少女性吸食可卡因的自我给药。与合成黄体酮相比，口服微粉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月经不规则出血。综上所述，这些发现表明口服微孕酮在减少寻求治疗的可卡因依赖妇女的可卡因使用方面可能具有临床效用。这一区域药物管理局的目标是支持药物滥用的临床试验试点，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，以评估口服微孕酮与安慰剂对依赖快克可卡因的女性的疗效。在药物滥用者的药物治疗试验中，最大的问题之一是依从性和保留性差。我们会使用代金券奖励诊所的就诊率，以提高依从性，我们会提供简短的依从性增强治疗。这一试验性治疗试验的结果将提供一个初步基础，以决定是否进行一项大规模临床试验，该试验将包括一组更多样化的妇女（即主要通过除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).