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

基本信息

批准号：
10832236
负责人：
AIMEE L MCRAE-CLARK
金额：
$ 10.57万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
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/10832236
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

项目摘要

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.

项目概要/摘要大麻使用障碍（CUD）很普遍，并与显着的临床后遗症相关。 CUD 可能因性别以及行为、生物学和临床相关性方面的性别差异而变得复杂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，并且更严重。合并精神疾病的可能性，而男性往往更早开始使用并且寿命更长在其他成瘾性疾病中，例如酒精使用障碍，临床试验终点为然而，迄今为止，还没有工作关注不同的临床相关终点是否存在。患有 CUD 的男性和女性可能需要减少大麻。在 CUD 试验中，使用是戒断的一个可行的替代终点，特别是在改变患者的情况下然而，缓解大麻合法化所需的减少量。 CUD 尚不清楚，而且男性和女性的情况可能有所不同，一项新兴文献表明卵巢激素与卵巢激素有关。临床前和临床研究表明，内源性黄体酮在药物使用中发挥着关键作用。最近的临床研究调查了外源性黄体酮的潜在作用。药物疗法已表明它可以减弱可卡因和烟草的主观和生理影响目前，对于药物依赖个体中黄体酮和 CUD 的相互作用知之甚少。黄体酮水平的波动可能会影响减少大麻使用的能力。通过实证推导大麻数量和使用频率的阈值，在 CUD 治疗研究中存在差距低于该值，大多数接受 CUD 治疗的人都可以实现 CUD 缓解。重要的是，性别的作用。考虑 CUD 结果中的卵巢激素，并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% 女性）将接受 8 周的治疗心理社会干预，包括计算机化 CBT4CBT 症状和详细信息。将收集参与者在 8 周治疗期间和 3 个月内的大麻使用情况随访（1、2 和 3 个月的随访）参与者将完成每日电子日记以加强。对自我报告的大麻数量和使用频率的评估，并通过每周对大麻的评估得到证实每天收集尿液大麻代谢物 11-nor-9-carboxy-Δ⁹-四氢大麻酚。黄体酮评估的分析将检查大麻减少的阈值是否必要。实现 CUD 缓解的方法因性别而异，并且黄体酮变化对成功的影响也不同减少大麻的目标的建立将具有现实世界的临床意义。治疗影响，并使未来的研究能够严格测试有希望的 CUD 候选治疗方法。