P.F. Renshaw, C.C. Streeter, Y Ke, D.P Olson, E.D. Rouse, L.E : MAGNETIC RESONANCE SPECTROSCOPY

Magnetic resonance spectroscopy (MRS) provides a non-invasive window on human brain chemistry. Over the last five years, we have completed several hydrogen (proton, IH) and phosphorus (31P) MRS studies of cocaine dependent (CD) subjects. Using 1H MRS, we have demonstrated that there are no reductions in the neuronal marker N-acetylaspartate (NAA) in CD but that there are changes in the transverse relaxation time (T2) of NAA in frontal cortex. This reduction in T2, which tends to normalize with treatment, is most consistent with a reduction in neuronal volume and may reflect changes in dopaminergic transmission as dopamine is a critical modulator of Na/K ATPase activity. We have also noted 15-20% reductions in frontal lobe GABA levels. GABA levels are elevated in CD subjects who are treated with adjunctive pharmacotherapy. Using 31P MRS, we have demonstrated increases in brain phosphomonoesters (PME ; phospholipids precursors) and decreases in brain nucleoside triphosphates (beta-NTP ; primarily adenosine triphosphate) in CD subjects. Based on these observations of stimulant-induced alterations in brain chemistry, we have completed preliminary studies on the efficacy cytidine diphosphoeholine (CDP-choline) as a potential treatment for CD. CDP-choline administration stimulates phospholipid synthsis. initial clinical trials suggest that CDP-choline can reduce not cocaine use, but also nicotine, alcohol, and marijuana use in CD subjects during early abstinence.