Gender and Sex Hormone Influences on Cannabis Use Disorder Remission

项目总结/摘要 大麻使用障碍（CUD）很普遍，并伴有严重的临床后遗症。有效治疗 对于CUD，可能会因行为、生物学和临床相关性方面的性别差异而复杂化 的CUD。女性表现出更严重的戒断症状，从首次使用到CUD的进展更快， 合并精神疾病的可能性，而男性倾向于更早开始使用， CUD的流行率。在其他成瘾性疾病中，如酒精使用障碍，临床试验终点是 性别/性别特异性。然而，迄今为止，没有工作集中在不同的临床相关终点是否 对于患有CUD的男性和女性可能需要。一位专家最近得出结论， 在CUD试验中，使用是禁欲的一个可行的替代终点，特别是在患者发生变化的情况下 优惠和大麻合法化的增长。然而，从缓解所需的减少量 CUD是未知的，可能对男性和女性不同。一项新的文献表明，卵巢激素 在毒品使用中起着关键作用。临床前和临床研究表明，内源性孕酮减弱 药物敏感性和行为。最近的临床研究调查外源性孕酮作为一种潜在的 药物治疗表明，它减弱了可卡因和烟草的主观和生理影响， 在依赖药物的人身上。目前，关于孕酮和CUD的界面知之甚少，如果 孕酮水平的波动可能会影响减少大麻使用的能力。这项提案涉及一个关键问题， CUD治疗研究中的差距，通过分析得出大麻数量和使用频率的阈值 低于该值，大多数接受CUD治疗的个体可以实现CUD缓解。重要的是，性别角色 和卵巢激素在CUD结局中的作用，并将得出性别特异性终点。 符合CUD标准的寻求治疗的成年人（N=224，年龄18岁以上，50%为女性）将接受8周的 心理社会干预，包括计算机化CBT 4CBT。CUD症状和详细信息 在为期8周的治疗期间和为期3个月的治疗期间， 随访（1、2和3个月随访访视）。参与者将完成每日电子日记， 对自我报告的大麻数量和使用频率进行评估，并通过每周评估一次 尿大麻代谢物，11-去甲-9-羧基-Δ N-四氢大麻酚。每天收集唾液样本 用于评估孕酮。分析将审查是否有必要减少大麻的门槛 达到CUD缓解的可能性因性别而异，孕酮的变化对成功缓解CUD的影响也因性别而异。 减少大麻。建立性别特异性降低终点将具有现实世界的临床意义， 治疗的影响，以及使未来的研究，以严格测试有前途的候选治疗CUD。

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.