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，从第一次使用到CUD的进展更快，而且更大 合并精神障碍的可能性，而男性倾向于更早开始使用和更长的寿命 CUD患病率。在其他成瘾性障碍中，如酒精使用障碍，临床试验终点为 性别/性别特定。然而，到目前为止，还没有研究集中于不同的临床相关终点 对于患有CUD的男性和女性可能需要。一个专家工作组最近得出结论，减少大麻 在CUD试验中，使用是禁欲的一个可行的替代终点，特别是在更换患者的情况下 优惠和日益合法化的大麻。然而，减免所需的减免额 CUD是未知的，男性和女性可能会有所不同。一项新的文献表明，卵巢激素 在药物使用中发挥关键作用。临床前和临床研究表明，内源性黄体酮可以减弱 药物敏感性和行为。近期临床研究外源性黄体酮作为一种潜在的 药物治疗表明，它可以减弱可卡因和烟草的主观和生理影响。 在药物依赖者身上。目前，关于黄体酮和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。这项建议解决了一个关键问题 通过经验推导大麻数量和使用频率的阈值在CUD治疗研究中的差距 低于这一点，大多数接受CUD治疗的患者可以实现CUD缓解。重要的是，性别的作用 以及卵巢激素在CUD结果中的作用，并将得出性别特定的终点。 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)将获得8周的 心理社会干预，包括计算机化的CBT4CBT。CUD症状和详细信息 在8周的治疗期间和3个月的治疗期间，将从参与者那里收集大麻使用情况 随访(1、2、3个月随访)。参加者将完成日常电子日记，以提高 自我报告的大麻数量和使用频率的评估，得到每周一次的 尿大麻代谢产物，11-或-9-羧基-Δ⁹-四氢大麻酚。每天都会采集唾液样本 用来评估黄体酮。分析将审查减少大麻的门槛是否必要 慢性阻塞性肺病的缓解因性别和孕酮变化对成功的影响而不同。 减少大麻。建立性别特定的减少终点将既有现实世界的临床 并使未来的研究能够严格测试有希望的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.