Effects of cytidine-5'-diphosphate choline on gray matter volumes in methamphetamine-dependent patients: A randomized, double-blind, placebo-controlled study

Abstract

Background: Cytidine-5'-diphosphate choline (CDP-choline) has been suggested to exert neuroprotective and neuroreparative effects and may be beneficial for patients with stimulant dependence. This randomized, double-blind, placebo-controlled study in methamphetamine (MA) dependence investigated effects of CDP-choline on the brain structures and their associations with craving and MA use.

Methods: MA users (n = 44) were randomized to receive 2 g/day of CDP-choline (n = 22) or placebo (n = 22) for 8 weeks. Patients underwent brain magnetic resonance imaging (MRI) at baseline and 8-week follow-up. Healthy individuals (n = 27) were also examined using brain MRI at the same interval. Voxel-based morphometry analysis was conducted to examine changes in gray matter (GM) volumes and their associations with craving and MA use.

Results: Craving for MA was significantly reduced after the 8 week-treatment with CDP-choline (p = 0.01), but not with the placebo treatment (p = 0.10). There was no significant difference in the total number of MA-negative urine samples between the two groups (p = 0.19). With CDP-choline treatment, GM volumes in the left middle frontal gyrus (p = 0.001), right hippocampus (p = 0.009), and left precuneus (p = 0.001) were significantly increased compared to the placebo and control groups. Increased GM volumes in the left middle frontal gyrus with CDP-choline treatment were associated with reduced craving for MA (Spearman's ρ = -0.56, p = 0.03). In addition, the right hippocampal volume increases were positively associated with the total number of MA-negative urine results in the CDP-choline group (Spearman's ρ = 0.67, p = 0.006).

Conclusion: Our findings suggest that CDP-choline may increase GM volumes of MA-dependent patients, which may be related to decreases in MA use and craving.

Keywords: Cytidine-5′-diphosphate choline; Gray matter volume; Magnetic resonance imaging; Methamphetamine.

Fig. 1.

Increases (red-yellow) or decreases (blue-green) in GM volume in methamphetamine-dependent patients after administration of CDP-choline (n = 15, p < 0.005 and 50 or more contiguous voxels). Significant changes in GM volume were found in 6 clusters and the numbers in parentheses show the cluster numbers (1 = left middle frontal gyrus, 2 = left supramarginal gyrus, 3 = right hippocampus, 4 = left middle temporal gyrus, 5 = left hippocampus, 6 = left precuneus). Detailed cluster information is listed in Table 2. The numbers above the brain slices indicate z coordinates in the Montreal Neurological Institute space. The color bar indicates t value at each voxel. CDP-choline, cytidine-5′-diphosphate choline; GM, gray matter; L, left; R, right.

Fig. 2.

Relationships between changes in craving or MA use and changes in gray matter volume in MA-dependent patients administered with CDP-choline (n = 15). (A) A significant negative correlation between changes in craving for MA and changes in volume of the left middle frontal gyrus (cluster number 1 in Table 2). (B) A significant positive association between number of MA-negative urine results and changes in volume of the right hippocampus (cluster number 3 in Table 2). CDP-choline, cytidine-5′-diphosphate choline; MA, methamphetamine.