Gender and Sex Hormone Influences on Cannabis Use Disorder Remission

性别和性激素对大麻使用障碍缓解的影响

• 批准号: 10615214
• 负责人: AIMEE L MCRAE-CLARK
• 金额: $ 42.64万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615214
• 关键词: Abstinence; Address; Adopted; Adult; Age; Attenuated; Behavior; Behavioral; Benchmarking; Biological; Cannabis; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Cocaine; Computerized Cognitive Behavioral Therapy; Development; Disease remission; Drug usage; Electronics; Empirical Research; Enrollment; Evaluation; Female; Frequencies; Future; Gender; Goals; Gonadal Steroid Hormones; Individual; Intervention; Literature; Mental disorders; Natural Increases; Online Systems; Outcome; Ovarian hormone; Participant; Patient Preferences; Patient Self-Report; Pattern; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Play; Prevalence; Progesterone; Risk; Role; Sampling; Self Assessment; Sex Differences; Standardization; Substance Use Disorder; Symptoms; Testing; Tetrahydrocannabinol; Therapeutic; Tobacco; Treatment outcome; Variant; Video Recording; Visit; Withdrawal; Woman; Work; addiction; alcohol use disorder; cannabis use behavior; clinically relevant; computerized; diaries; drug sensitivity; effective therapy; follow-up; gender difference; marijuana legalization; marijuana use; marijuana use disorder; men; milligram; mobile application; pre-clinical research; psychiatric comorbidity; psychosocial; saliva sample; sample collection; sex; social; therapy development; treatment duration; treatment program; treatment research; urinary

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.

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更大，而男性倾向于更早开始使用， CUD的终生流行率。在其他成瘾性疾病中，如酒精使用障碍，临床试验 终点具有性别特异性。然而，迄今为止，没有工作集中在是否不同的临床 对于患有CUD的男性和女性，可能需要相关终点。一位专家最近总结说， 减少大麻使用是CUD试验中禁欲的一个可行的替代终点，特别是在 改变患者偏好和大麻合法化的背景下。然而，减少的数量 缓解CUD的必要条件未知，男性和女性可能不同。新兴文学 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疗法已经表明，它减弱了主观的， 可卡因和烟草对药物依赖者的生理影响。目前，我们所知甚少， 孕酮和CUD的界面，以及孕酮水平的波动是否可能影响降低 使用大麻该提案通过简化推导，解决了CUD治疗研究中的一个关键空白。 大麻数量和使用频率的阈值，低于该阈值，大多数接受CUD治疗的人可以 实现CUD缓解。重要的是，性别和卵巢激素在CUD结局中的作用是 将得出考虑的和性别特异性终点。符合CUD标准的寻求治疗的成人 （N=224，年龄18岁以上，50%女性）将接受8周的心理社会干预，包括计算机 CBT4CBT。CUD症状和有关大麻使用的详细信息将在 8周治疗期和3个月随访期间（1、2和3个月随访访视）。 参与者将填写每日电子日记，以加强对自我报告的大麻数量的评估 和使用频率，通过每周评估尿大麻代谢物11-去甲-9-羧基- Δ β-四氢大麻酚。每天收集唾液样本用于评估孕酮。分析将 检查实现CUD缓解所需的大麻减少阈值是否不同， 性别和孕酮的变化对成功减少大麻的影响。建立 性别特异性降低终点将具有现实世界的临床治疗意义， 未来的研究将严格测试有希望的CUD候选治疗方法。