Gender and Sex Hormone Influences on Cannabis Use Disorder Remission

项目摘要/摘要 大麻使用障碍(CUD)很普遍，并与严重的临床后遗症有关。有效治疗 对于CUD来说，行为、生物学和临床相关的性别和性别差异可能使其复杂化。 当然。女性表现出更严重的戒断，从首次使用到CUD的进展更快，以及 合并精神障碍的可能性更大，而男性倾向于更早开始使用，并有更高的风险 CUD终生患病率。在其他成瘾障碍中，如酒精使用障碍，临床试验 终端是特定于性别/性别的。然而，到目前为止，还没有研究集中在临床上是否存在不同 患有CUD的男性和女性可能需要相关的终点。一个专家工作组最近得出结论 在戒毒试验中，减少大麻使用是戒断的一个可行的替代终点，特别是在 在改变患者偏好和日益合法化大麻的背景下。然而，减少的数量 缓解CUD所需的条件尚不清楚，男性和女性可能会有所不同。一种新兴文学 这表明卵巢激素在药物使用中起着关键作用。临床前和临床研究表明 内源性黄体酮可降低药物敏感性和行为。最近的临床研究调查 外源性黄体酮作为一种潜在的药物治疗方法，已表明它可以减轻主观和 可卡因和烟草对药物依赖者的生理影响。目前，人们对此知之甚少 孕酮与CUD的界面，以及孕酮水平的波动是否可能影响降低 吸食大麻。这项建议解决了CUD治疗研究中的一个关键空白，通过经验推导出 大麻数量和使用频率的阈值，低于这一阈值的大多数接受戒毒治疗的人可以 实现CUD的缓解。重要的是，性别和卵巢激素在CUD结果中的作用是 将得出经过考虑的和特定于性别的端点。符合CUD标准的寻求治疗的成年人 (n=224人，年龄18岁以上，50%为女性)将接受为期8周的心理社会干预，包括计算机化 CBT4CBT.将从参与者那里收集有关大麻使用的CUD症状和详细信息 治疗8周，随访3个月(1、2、3个月)。 参加者将完成每日电子日记，以加强对自行申报的大麻数量的评估 和使用频率，通过每周对尿中大麻代谢物11-Nor-9-Carxy的评估来证实- Δ⁹-四氢大麻酚。每天都会采集唾液样本，以评估孕激素水平。分析将 审查实现戒毒缓解所需的大麻减少量的门槛是否有以下不同 性别和孕酮变化对成功减少大麻的影响。成立了 特定性别的减少终点将既具有现实世界的临床治疗意义，也将使 未来的研究将严格测试有希望的CUD候选治疗方法。

PROJECT SUMMARY/ABSTRACT Cannabis use disorder (CUD) is prevalent and associated with significant clinical sequelae. Effective treatment for CUD may be complicated by gender and sex differences in the behavioral, biological, and clinical correlates of CUD. Women demonstrate more severe withdrawal, more rapid progression from first use to CUD, and greater likelihood of comorbid psychiatric disorder, while men tend to initiate use earlier and have higher lifetime prevalence rates of CUD. In other addictive disorders, such as alcohol use disorder, clinical trial endpoints are sex/gender specific. However, to date, no work has focused on whether different clinically relevant endpoints may be needed for men and women with CUD. An expert workgroup recently concluded that reduced cannabis use is a viable alternative endpoint to abstinence in CUD trials, particularly in the context of changing patient preferences and growing cannabis legalization. However, the amount of reduction necessary for remission from CUD is unknown and may differ for men and women. An emerging literature suggests that ovarian hormones play a key role in drug use. Preclinical and clinical research suggests that endogenous progesterone attenuates drug sensitivity and behavior. Recent clinical studies investigating exogenous progesterone as a potential pharmacotherapy have shown that it attenuates the subjective and physiological effects of cocaine and tobacco in drug-dependent individuals. Presently, little is known regarding the interface of progesterone and CUD, and if fluctuations in progesterone levels may impact ability to reduce cannabis use. This proposal addresses a key gap in CUD treatment research by empirically-deriving the threshold of cannabis quantity and frequency of use below which most individuals in CUD treatment can achieve CUD remission. Importantly, the roles of gender and ovarian hormones in CUD outcomes are considered and gender-specific endpoints will be derived. Treatment-seeking adults who meet criteria for CUD (N=224, ages 18+, 50% female) will receive 8 weeks of a psychosocial intervention, including computerized CBT4CBT. CUD symptoms and detailed information on cannabis use will be collected from participants during the 8-week treatment period and during a three month follow-up (1, 2, and 3 month follow-up visits). Participants will complete daily electronic diaries to enhance assessment of self-reported cannabis quantity and frequency of use, corroborated by weekly assessment of a urinary cannabis metabolite, 11-nor-9-carboxy- Δ⁹-tetrahydrocannabinol. Daily saliva samples will be collected for assessment of progesterone. Analyses will examine whether the threshold for cannabis reduction necessary to achieve remission from CUD differs by gender and the effect of variation in progesterone on successful cannabis reduction. The establishment of gender-specific reduction endpoints will have both real-world clinical treatment implications as well as enable future studies to rigorously test promising candidate treatments for CUD.