Citicoline for Alcohol Dependence

描述（由申请人提供）：酒精依赖是一个主要的公共健康问题，发病率很高，其不良后果包括失业、法律问题和预期寿命缩短。因此，需要新的和有效的治疗方法。我们小组对药物依赖进行评估。我们研究的一种特别有前途的药物是胞胆碱，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。胞胆碱具有神经保护作用，可改善包括血管性痴呆在内的多种神经系统疾病的认知能力。因此，胞胆碱可能代表了一种针对促进和延续物质使用的认知过程缺陷（如执行功能、决策、记忆）的物质使用障碍的新方法。我们小组进行了一项随机、安慰剂对照的双相情感障碍和可卡因依赖的初步研究，结果表明胞胆碱耐受性良好，与减少可卡因和酒精的使用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患者中尤为明显。这一发现与另外两项关于胞胆碱的小型研究一致

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.