A second line of evidence concerns the potential therapeutic value N-acetyl-cysteine (NAC) in the treatment of neuropsychiatric conditions closely related to TS including Trichotillomania (TTM) and Obsessive-compulsive disorder [OCD]. Recent double-blind, placebo-controlled studies of NAC have provided evidence of efficacy in reducing the symptoms of trichotillomania (TTM) in adults [49]. The effect size in this 12-week study was strikingly large (d = 1.3). Trichotillomania, like TS, is considered to be an obsessive-compulsive spectrum disorder. Individuals with TTM experience urges prior to hairpulling, similar to the urges in TS. Case reports have also suggested the potential efficacy of NAC in treating OCD. NAC is hypothesized to have two possible mechanisms of action. NAC is converted to cystine, a substrate for the glutamate/cystine antiporter located on glial cells. The uptake of cystine by glia causes the release of glutamate into the extrasynaptic space, where it stimulates inhibitory metabotropic glutamate receptors on glutamatergic nerve terminals and thereby reduces the synaptic release of glutamate. NAC is also a precursor of glutathione, the major antioxidant in the brain. Through this mechanism NAC is hypothesized to improve OXPHOS. One effect of EPI-743's activity on NQO1 is restoration of cellular glutathione stores.