Citicoline for Alcohol Dependence

描述（由申请人提供）：酒精依赖是一个主要的公共卫生问题，患病率很高，不良后果包括失业、法律的问题和预期寿命缩短。因此，需要新的和有效的治疗方法。我们的小组评估药物依赖。我们研究的一种特别有前途的药物是胞磷胆碱，它是一种调节胆碱能系统和膜磷脂代谢的药物。这些都是治疗酒精依赖的新机制。胞磷胆碱具有神经保护特性，并改善包括血管性痴呆在内的各种神经系统疾病的认知。因此，胞磷胆碱可能代表了一种新的方法，以物质使用障碍为目标，在认知过程（如执行功能，决策，记忆），促进和延续物质使用的缺陷。我们的研究小组对双相情感障碍和可卡因依赖进行了一项随机，安慰剂对照的初步研究，表明胞磷胆碱耐受性良好，并且与可卡因和酒精使用的减少以及执行功能和记忆的改善有关。认知能力的改善在酒精使用障碍的亚组中特别明显。这一发现与另外两项关于胞磷胆碱的小型研究一致， 它可以减少酒精的使用。在目前的应用中，我们提出了一个试点研究胞磷胆碱在酒精依赖。胞磷胆碱是大脑中天然存在的化合物，具有非常有利的副作用和安全性，并且相对便宜。因此，如果胞磷胆碱能有效地减少酒精的使用，它可能是一种实用的治疗方法，会被患者很好地接受。本申请提出了一个为期12周的随机，双盲，安慰剂对照试验的胞磷胆碱在62个门诊病人与酒精依赖。参与者将每周进行评估，以评估自我报告的酒精使用和渴望。每4周评估一次执行功能、注意力、冲动性、工作记忆和陈述性记忆。我们假设胞磷胆碱治疗与减少饮酒和改善认知有关。如果这项初步研究的数据有希望，将用于设计更大规模的试验。

DESCRIPTION (provided by applicant): Alcohol dependence is a major public health concern with a high prevalence, and adverse consequences that include unemployment, legal problems, and shortened life expectancy. Thus, new and effective treatments are needed. Our group evaluates medications for substance dependence. A particularly promising medication that we have investigated is citicoline, an agent that modulates cholinergic systems and membrane phospholipid metabolism. These are new and novel mechanisms for treating alcohol dependence. Citicoline has neuroprotective properties and improves cognition in a variety of neurological disorders including vascular dementia. Thus, citicoline may represent a new approach to substance use disorders targeting deficits in cognitive processes (e.g. executive functioning, decision making, memory) that facilitate and perpetuate substance use. Our group conducted a randomized, placebo-controlled pilot study in bipolar disorder and cocaine dependence that suggested that citicoline was well tolerated, and was associated with a reduction in both cocaine and alcohol use we well as improvement in executive functioning and memory. The improvement in cognition was particularly robust in the subset with alcohol use disorders. The findings are consistent with two other small studies of citicoline that suggest that it may reduce alcohol use. In the current application, we propose a pilot study of citicoline in alcohol dependence. Citicoline is a naturally occurring compound in the brain that has a very favorable side effect and safety profile and is relatively inexpensive. Thus, if effective in reducing alcohol use, citicoline might be a practical treatment that would be well accepted by patients. This application proposes a 12-week randomized, double-blind, placebo-controlled trial of citicoline in 62 outpatients with alcohol dependence. Participants will be evaluated weekly for assessment of self-reported alcohol use and craving. Executive functioning, attention, impulsivity, and working and declarative memory will be assessed every 4 weeks. We hypothesize that citicoline therapy will be associated with decreased alcohol use and improved cognition. The data from this pilot study, if promising, will be used to inform the design of a larger trial.