N-acetylcysteine and its use in the treatment of addictive disorders

N-acetylcysteine (NAC) is a cystine pro-drug that promotes the synthesis of glutathione and activates the cystine-glutamate exchanger (often referred to as system xc-). Traditionally, NAC has been used as a mucolytic agent and for the treatment of acetaminophen overdose. However, via its actions on system xc-, NAC restores extraneuronal glutamate homeostasis and has been shown to prevent reinstatement of cocaine- and nicotine-seeking behavior in animal models of drug addiction. There are also clinical findings that NAC attenuates cocaine cue reactivity and intake as well as cigarette smoking, and recent evidence suggests that NAC also may be of potential use in the treatment of behavioral addictions such as compulsive gambling and certain forms of self-injurious behaviors. In this chapter, the neurochemical mechanisms of action of NAC with regards to its ability to regulate glutamate homeostasis and its ability to reduce reinstatement of drug-seeking behavior will be reviewed. Findings from the handful of clinical trials that have provided support for the potential use of NAC in the treatment of drug and non-drug addictions will also be summarized.