Citicoline for Alcohol Dependence

描述(申请人提供)：酒精依赖是一个主要的公共卫生问题，具有很高的流行率，并产生包括失业、法律问题和缩短预期寿命在内的不良后果。因此，需要新的有效的治疗方法。我们小组对药物的物质依赖性进行评估。我们研究的一种特别有希望的药物是胞磷胆碱，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。胞二磷胆碱具有神经保护特性，可改善包括血管性痴呆在内的各种神经疾病的认知能力。因此，胞二磷胆碱可能代表了一种新的治疗物质使用障碍的方法，目标是促进和维持物质使用的认知过程(如执行功能、决策、记忆)的缺陷。我们小组在双相情感障碍和可卡因依赖方面进行了一项随机、安慰剂对照的初步研究，结果表明胞二磷胆碱耐受性良好，与可卡因和酒精使用量的减少以及执行功能和记忆力的改善有关。在有酒精使用障碍的亚组中，认知能力的改善尤其明显。这一发现与另外两项关于胞磷胆碱的小型研究一致，这两项研究表明 它可能会减少酒精的使用。在目前的应用中，我们建议对胞二磷胆碱进行酒精依赖的初步研究。胞二磷胆碱是一种在大脑中自然产生的化合物，具有非常有利的副作用和安全性，而且相对便宜。因此，如果在减少酒精使用方面有效，胞二磷胆碱可能是一种被患者很好地接受的实际治疗方法。这项申请提出了一项为期12周的随机、双盲、安慰剂对照试验，对62名酒精依赖门诊患者进行胞二磷胆碱治疗。参与者将每周接受一次评估，以评估自己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、工作记忆和陈述性记忆。我们假设胞磷胆碱治疗将与减少酒精使用和改善认知有关。这项先导性研究的数据，如果前景看好，将被用于设计一项更大规模的试验。

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.