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

项目总结 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 有效治疗合并创伤后应激障碍(PTSD)的酒精使用障碍(AUD)。CBD 目前是医学研究的焦点，因为它显示出治疗焦虑和其他大脑疾病的希望，但不是 它与大麻的其他部分一样产生“快感”，没有被证明会上瘾，而且是安全的，几乎没有副作用。 AUD是最常见和最令人衰弱的精神疾病之一，通常与其他 共病精神障碍--尤其是创伤后应激障碍：根据研究人群的不同，30%-60%的有 澳大利亚也有创伤后应激障碍，退伍军人的共病发生率很高。来自动物模型和临床研究的证据 这表明，创伤后应激障碍症状引起的负面情绪会在戒酒过程中加剧对酒精的渴望， 使成瘾循环永久化；此外，有证据表明，大脑循环产生负面情绪和成瘾 它们连接在前脑区域，称为延伸的杏仁核，它提供了神经药物靶点 同时治疗AUD和PTSD患者的负面情绪和酒精成瘾。CBD是众所周知的 抑制延伸的杏仁核中的大脑活动，导致动物模型和人类的焦虑减轻。CBD还 在动物模型中减少上瘾的酒精寻求。 在这个项目中，我们的目标是检验口服CBD将减少AUD患者饮酒的假设 与创伤后应激障碍并存。为了验证这一假设，50名患有中度或重度AUD的健康成年参与者 创伤后应激障碍将随机接受CBD(每天400毫克)或安慰剂治疗，为期6周，如 参与者和研究人员都对治疗条件视而不见。我们将收集有关酒精的基线和每周数据 使用情况和创伤后应激障碍症状，并评估CBD治疗是否导致这些措施相对更大的改善 对于安慰剂，以及减少饮酒是否与创伤后应激障碍症状的改善暂时相关。科目 我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 由再次经历创伤后应激障碍和酗酒所产生。任务将在基线管理，在此之前 治疗后6周复查。我们将比较与治疗相关的酒精渴求的减少 CBD组和安慰剂组之间由创伤相关的负面情绪引起的。这项研究将是第一个测试 CBD在治疗酒精成瘾和人类创伤后应激障碍方面是否有效，以及第一个检查 这些处理效果之间的相互作用。结果将作为概念的验证，并为未来更大的 临床试验。由于CBD是一种安全、容易获得的药物，这样的试验将具有巨大的预防潜力 与AUD和PTSD相关的死亡、疾病和心理痛苦。此外，因为大脑通过 相对较好地理解CBD的哪些行为会产生假想的影响，结果可能会大幅提升 了解酒精成瘾的神经生物学基础。

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.