NAC Normalizes Glutamate Levels in Cocaine-Dependent People

May 28, 2013 · Posted in Potential Treatments 

cocaine userGlutamate is the major excitatory neurotransmitter in the brain, while GABA is the main inhibitory neurotransmitter. Too much or too little of one or the other can lead to an imbalance in neuronal communication. In a 2012 study by Schmaal et al. published in the journal Neuropsychopharmacology, cocaine-dependent patients were found to have high levels of glutamate in the dorsal anterior cingulate cortex. A single administration of N-acetylcysteine (NAC) at a dose of 2400mg lowered these levels.

Healthy (non-addicted) participants who received the same administration of NAC did not show the same drop in glutamate levels.

The study also observed levels of impulsivity in the patients. Higher baseline levels of glutamate were associated with greater impulsivity, and both higher baseline level of glutamate and greater impulsivity were predictive of a larger drop in glutamate levels following NAC administration.

The researchers suggest that these findings may eventually be used in the treatment of cocaine-addicted people, since abnormal glutamate levels are related to risk of relapse. In drug-dependent rodents, NAC was found to normalize hyper-responsive glutamate release in the nucleus accumbens (the brain’s reward center) and prevent cocaine-reinstatement or relapse.

Editor’s Note: When these data from the lab of Peter Kalivas at the Medical University of South Carolina were initially collected, it was thought that NAC’s effect on a cystine-glutamate exchanger in the nucleus accumbens explained its treatment success, but new data suggest that NAC may actually facilitate glutamate clearance by increasing the number of glutamate transporters in glial cells.


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