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：
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
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/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

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，并且合并精神疾病的可能性更大，而男性往往更早开始使用并且有更高的在其他成瘾性疾病中，例如酒精使用障碍，临床试验中 CUD 的终生患病率。终点是特定于性别的，但是迄今为止，还没有研究关注临床上是否存在不同。患有 CUD 的男性和女性可能需要相关终点。一个专家工作组最近结束。减少大麻使用是 CUD 试验中戒断的一个可行的替代终点，特别是在然而，患者偏好改变和大麻合法化的背景下，减少的数量。缓解 CUD 的必要条件尚不清楚，并且对于男性和女性可能有所不同一项新兴文献。表明卵巢激素在药物使用中发挥着关键作用。最近的临床研究调查了内源性黄体酮会减弱药物敏感性和行为。外源性黄体酮作为一种潜在的药物疗法已表明它可以减弱主观和目前，人们对可卡因和烟草对药物依赖者的生理影响知之甚少。黄体酮和 CUD 的界面，黄体酮水平的波动是否会影响降低的能力该提案通过实证推导解决了 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 治疗的人可以重要的是，性别和卵巢激素在 CUD 结局中的作用是。将得出符合 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 周的心理社会干预，包括计算机化干预 CBT4CBT。期间将从参与者收集 CUD 症状和有关大麻使用的详细信息。 8 周治疗期和三个月随访期间（1、2 和 3 个月随访）。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的评估和使用频率，通过每周评估尿中大麻代谢物 11-nor-9-carboxy- 得到证实将收集每日唾液样本以进行黄体酮分析。检查实现 CUD 缓解所需的大麻减少阈值是否不同性别和黄体酮变化对成功减少大麻的影响。特定性别的减少终点不仅具有现实世界的临床治疗意义，而且能够未来的研究将严格测试有希望的 CUD 候选治疗方法。