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The prevalence and impact of drug addiction on society are staggering. The abuse of alcohol, tobacco, and illicit drugs accounts for approximately 10% of the global burden of disease, and for the United States, it is estimated that substance use disorders affect 20.4 million individuals.1 Despite the deleterious economic and social consequences of drug use, approved medications to treat substance use disorders are few or absent depending on the drug. We and others have explored the possibility that dysregulation in prefrontal and allocortical (amygdala and hippocampus) glutamatergic inputs to the basal ganglia may be a mechanism responsible for relapse that is shared between classes of addictive drugs, as well as other disorders characterized by maladaptive compulsive behavior. Herein, we describe the bench-to-bedside chronology of preclinical discovery and clinical trials that led to the cysteine prodrug N-acetylcysteine being evaluated for the treatment of substance abuse and compulsive disorders.
Brown RM, Kupchik YM, Kalivas PW. The Story of Glutamate in Drug Addiction and of N-Acetylcysteine as
a Potential Pharmacotherapy. JAMA Psychiatry. 2013;70(9):895-897. doi:10.1001/jamapsychiatry.2013.2207