Effects of Citicoline on Brain Function and Behavior in Marijuana-Dependent Individuals

The Three Aims of this study are (only studies for Aim 1 were completed) Measure the impact of citicoline on marihuana use patterns in subjects' individualized natural settings and responses to marihuana challenge using functional brain MRI scans. Hypothesis - 2 g/day citicoline will produce greater reductions in marihuana use and craving in heavy marihuana users than placebo citicoline over a 8-week treatment period as measured in their natural environments. The same participants will experience greater improved brain activation patterns and an improvement in cognitive functioning compared to placebo controlled subjects. Measure the effects of citicoline on marihuana absorption and metabolism and determine if these changes parallel changes in subjective and physiological responses in a laboratory setting. Hypothesis - Chronic (8 weeks) treatment with 2 g/day citicoline will produce increases in subjective and physiological effects of both acute marihuana smoking and placebo marihuana smoking compared to chronic placebo citicoline. Citicoline will have no effect on marihuana pharmacokinetics. Measure the effects of citicoline on marijuana-induced cue-induced craving and brain electrical activity (EEG). Hypothesis - Chronic (8 weeks) treatment with 2 g/day citicoline will reduce objective measures of marijuana cue-reactivity, and subjective reports of craving in response to marihuana cues will also be attenuated compared to chronic placebo citicoline treatment.

Marijuana dependence is an important public health problem in the United States, yet still no effective therapies are available. It is unclear how marijuana affects brain function after acute or chronic use. Knowing about the changes in brain function during marijuana dependence would aid in the understanding of the neurobiological basis of marijuana abuse and serve as a foundation for the development of new treatment medications for this disorder. New and improved brain imaging techniques, such as functional MRI (fMRI) and magnetic resonance spectroscopy (MRS), allow the viewing of these subtle, yet important, changes in brain function. Citicoline is used to treat victims of head trauma and neurodegenerative disorders. It has been found to be effective in reducing cocaine use and craving, and it has no known side effects. It has also been shown to reduce marijuana use. This is likely due to citicoline's ability to reduce insomnia and craving, act as a mild antidepressant, and improve cognitive function. How citicoline reduces drug use may be related to effects on cerebral blood flow and/or brain phospholipid metabolism in the reward areas of the brain. This study will determine whether citicoline alters marijuana use patterns, reduces craving, and affects brain phospholipids and metabolism in marijuana-dependent people. The outcome of the study could offer important insights into the pathophysiology and course of marijuana dependence. Furthermore, this study's outcome could potentially relate to other drug dependence disorders.

Inclusion Criteria: Meets DSM-IV criteria for current marijuana dependence Women with a negative pregnancy test prior to study entry Heavy smoker, defined as smoking more than 10 joints per week Exclusion Criteria: Abnormal electrocardiogram (ECG) Medical disorder that requires prescription medication Psychiatric disorder that requires prescription medication Abnormal liver function tests Taking herbal preparations Taking any over-the-counter medications on a chronic basis Pregnancy or breast feeding Neurological, infectious, or neoplastic disease Currently seeking treatment for marijuana abuse Meets criteria for alcohol, cocaine, or opioid dependence

Bracken BK, Penetar DM, Rodolico J, Ryan ET, Lukas SE. Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults. Pharmacol Biochem Behav. 2011 Jun;98(4):518-24. doi: 10.1016/j.pbb.2011.03.003. Epub 2011 Mar 21.