Citicoline for Alcohol Dependence

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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.