A randomised controlled trial of N-acetylcysteine for the treatment of alcohol use disorder

We urgently require new treatment strategies for alcohol use disorders (AUDs). Australian hospital admissions for alcohol-related disorders, in particular alcoholic liver disease, have continued to rise despite falling per-capita alcohol consumption. This paradox suggests that high-risk drinkers are not responding well to public health measures although low risk drinkers have reduced their consumption. Treatment options are currently limited. Effectiveness of medications currently listed on the PBS are variable and are not suitable for many patients with comorbidities such as those with advanced liver disease and mood disorders. N-acetylcysteine (NAC) is an antioxidant that also normalises expression of the glutamate transporter and restores glutamate homeostasis which is a key neurobiological component of AUD. It is orally active in the proposed regimen, low cost, clinically accessible and safe. Recent studies demonstrate that NAC robustly reduces alcohol seeking and relapse behaviours in experimental animals. Our world-first pilot trial reveals signals of efficacy and a good safety profile. We now propose to undertake a mutli-site RCT of NAC for the management of alcohol use disorder (NAC-AUD). The NAC-AUD project will evaluate the efficacy and cost-efficacy of NAC on drinking outcomes. A sample of 280 individuals will receive 12 weeks of treatment with NAC (2400 mg/day) or placebo using a double-blind, randomised, controlled trial. This highly experienced research team is made up of world-leading alcohol researchers and thus is uniquely qualified to complete this novel project. This project will be the first of its kind internationally and the results will generate high level clinical evidence for an inexpensive and safe new treatment for a life threatening disease.