Cannabidiol as a treatment for alcohol use disorder comorbid with posttraumatic stress disorder

大麻二酚用于治疗伴有创伤后应激障碍的酒精使用障碍

基本信息

批准号：
9436640
负责人：
Charles R. Marmar
金额：
$ 24.37万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-10 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9436640
关键词：
Address Adult Adverse effects Affect Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcohols Amygdaloid structure Animal Model Anti-Anxiety Agents Anti-Inflammatory Agents Anti-inflammatory Anxiety Area Arousal Brain Brain Diseases Cannabidiol Cannabis Cessation of life Clinical Clinical Research Clinical Trials Cognitive Comorbidity Cues Data Diagnosis Disease Dose Double-Blind Method Economic Burden Emotions Extinction (Psychology)Fright Functional Magnetic Resonance Imaging Functional disorder Future Goals Healthcare Heterogeneity Human Imagery Individual Laboratories Laboratory Study Life Link Measures Medical Medical Research Mental disorders Military Personnel Moods National Institute on Alcohol Abuse and Alcoholism Negative Reinforcements Neurobiology Oral Outpatients Participant Patient Self-Report Patients Pharmaceutical Preparations Pharmacology Physiological Placebos Plants Population Population Study Post-Traumatic Stress Disorders Prosencephalon Psychophysiology Randomized Reporting Research Safety Symptoms Testing Therapeutic Time Trauma Veterans Withdrawal Symptom addiction alcohol abuse therapy alcohol comorbidity alcohol craving alcohol seeking behavior alcohol use disorder blind design disability drug candidate experience improved longitudinal human study negative affect neurobiological mechanism novel preclinical study prevent psychologic randomized trial reduced alcohol use response social stress disorder treatment effect treatment response trial comparing

项目摘要

PROJECT SUMMARY This project aims to determine whether cannabidiol (CBD), a compound derived from the cannabis plant, is effective in treating alcohol use disorder (AUD) in individuals with comorbid posttraumatic stress disorder (PTSD). CBD is currently a medical research focus because it shows promise for treating anxiety and other brain disorders, but does not produce a `high' like other parts of cannabis, has not been shown to be addictive, and is safe, with few or no side effects. AUD, which is one of the most common and most debilitating psychiatric conditions, is often associated with other comorbid psychiatric disorders – in particular, PTSD: depending on the population studied, 30–60% of individuals with AUD also have PTSD, with high comorbidity rates in military veterans. Evidence from animal models and clinical studies suggests that the negative emotion caused by PTSD symptoms intensifies craving for alcohol during alcohol withdrawal, perpetuating the addictive cycle; further, evidence shows that the brain circuits underlying negative emotion and addiction are linked in a forebrain area called the extended amygdala, which provides a neuropharmacological target to simultaneously treat both negative emotion and alcohol addiction in individuals with AUD and PTSD. CBD is known to inhibit brain activity in the extended amygdala, leading to reduced anxiety in both animal models and humans. CBD also reduces addictive alcohol seeking in animal models. In this project, we aim to test the hypothesis that oral CBD will reduce alcohol drinking in individuals with AUD comorbid with PTSD. To test this hypothesis, 50 otherwise healthy adult participants with moderate or severe AUD and PTSD will be randomized to treatment with either CBD (400 mg per oral daily) or placebo, for a period of 6 weeks, such that both participants and study staff are blind to treatment condition. We will collect baseline and weekly data on alcohol usage and PTSD symptoms, and assess whether CBD treatment leads to a greater improvement in these measures relative to placebo, and whether reduction in alcohol drinking is temporally linked to improvement in PTSD symptoms. Subjects will also participate in a task designed to quantify the psychological and physiological links between negative emotion produced by re-experiencing PTSD trauma, and alcohol craving. The task will be administered at baseline, before treatment, and following 6 weeks of treatment. We will compare the treatment-associated reduction in alcohol craving elicited by trauma-associated negative emotion between CBD and placebo groups. This study will be the first to test whether CBD is effective in treating alcohol addiction and in treating PTSD in humans, and the first to examine the interaction between these treatment effects. Results will serve as proof of concept and provide guidance for a future larger clinical trial. Because CBD is a safe, readily available drug, such a trial would have an immense potential to prevent death, medical illness, and psychological suffering associated with AUD and PTSD. Further, because the brain circuits via which CBD acts to produce hypothesized effects are relatively well-understood, results may substantially advance understanding of the neurobiological basis of alcohol addiction.

项目概要该项目旨在确定大麻二酚 (CBD)（一种从大麻植物中提取的化合物）是否是可有效治疗患有创伤后应激障碍（PTSD）的个体的酒精使用障碍（AUD）。目前是医学研究的焦点，因为它显示出治疗焦虑和其他脑部疾病的希望，但并没有与大麻的其他部分一样，它会产生“快感”，尚未被证明具有成瘾性，而且安全，副作用很少或没有。 AUD 是最常见和最使人衰弱的精神疾病之一，通常与其他疾病相关共病精神疾病——尤其是创伤后应激障碍（PTSD）：根据研究人群的不同，30-60% 的人患有 AUD 还患有创伤后应激障碍 (PTSD)，来自动物模型和临床研究的证据表明，退伍军人的合并症率很高。表明 PTSD 症状引起的负面情绪会在戒酒期间加剧对酒精的渴望，进一步，有证据表明，大脑回路是负面情绪和成瘾的基础。连接在称为扩展杏仁核的前脑区域，该区域提供了神经药理学目标已知可以同时治疗 AUD 和 CBD 患者的负面情绪和酒精成瘾。抑制扩展杏仁核的大脑活动，从而减少动物模型和人类的焦虑。减少动物模型中成瘾的酒精寻求。在这个项目中，我们的目标是测试口服 CBD 会减少 AUD 患者饮酒的假设为了检验这一假设，50 名患有中度或重度 AUD 的健康成年参与者 PTSD 将随机接受 CBD（每日口服 400 毫克）或安慰剂治疗，为期 6 周，例如参与者和研究人员都对治疗状况视而不见，我们将收集有关酒精的基线和每周数据。的使用和 PTSD 症状，并评估 CBD 治疗是否会导致这些措施相对于安慰剂，以及减少饮酒是否与 PTSD 症状的改善暂时相关。还将参与一项旨在量化负面情绪之间的心理和生理联系的任务该任务将在基线之前进行。治疗后，以及治疗 6 周后，我们将比较治疗相关的酒精渴望减少情况。这项研究将是第一个测试 CBD 和安慰剂组之间由创伤相关的负面情绪引起的。 CBD 是否能有效治疗人类酒精成瘾和创伤后应激障碍 (PTSD)，并且是第一个检验这些治疗效果之间的相互作用将作为概念证明并为未来更大的治疗提供指导。由于 CBD 是一种安全、容易获得的药物，因此此类试验具有预防的巨大潜力。与 AUD 和 PTSD 相关的死亡、医疗疾病和心理痛苦此外，因为大脑回路通过。 CBD 发挥哪些作用来产生显着效果相对容易理解，结果可能会大幅推进了解酒精成瘾的神经生物学基础。