Previous studies have shown significantly lower metabolism and functional activity in the anterior cingulate cortex (ACC) of human cocaine addicts. The present study examined whether this ACC hypoactivity is associated with altered glutamate (Glu), the primary excitatory neurotransmitter in the central nervous system (CNS), which has been recently implicated in drug addiction. Participants comprised 14 chronic cocaine addicts and 14 matched healthy volunteers who were examined using (1)H magnetic resonance spectroscopy at 3 T. A new quantification strategy for echo time (TE)-averaged point-resolved spectroscopy (PRESS) was applied to disentangle relaxation effects from J-evolution of coupled spin systems such as Glu. The concentrations of Glu as well as N-acetyl aspartate (NAA), total creatine (tCr), choline-containing compounds (tCho), and myo-inositol (Ins) were estimated from both groups. Glu/tCr was significantly lower in chronic cocaine users compared to control subjects and was significantly correlated with years of cocaine use. Glu/tCr was also positively correlated with NAA/tCr. NAA/tCr significantly decreased with age but was not significantly different between the two groups. These findings suggest a metabolic/neurotransmitter dysregulation associated with cocaine addiction and support a possible therapeutic intervention strategy aimed at normalizing the Glu transmission and function in the treatment of cocaine addiction.