Investigating N-acetylcysteine as a Possible Pharmacologic Treatment for PTSD & SUD

Research Paper Title

A Double-Blind, Randomised, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Post-traumatic Stress Disorder and Substance Use Disorders.


The antioxidant N-acetylcysteine is being increasingly investigated as a therapeutic agent in the treatment of substance use disorders (SUDs). This study explored the efficacy of N-acetylcysteine in the treatment of post-traumatic stress disorder (PTSD), which frequently co-occurs with SUD and shares impaired pre-frontal cortex regulation of basal ganglia circuitry, in particular at glutamate synapses in the nucleus accumbens.


Veterans with PTSD and SUD per DSM-IV criteria (N = 35) were randomly assigned to receive a double-blind, 8-week course of N-acetylcysteine (2,400 mg/d) or placebo plus cognitive-behavioural therapy for SUD (between March 2013 and April 2014). Primary outcome measures included PTSD symptoms (Clinician-Administered PTSD Scale, PTSD Checklist-Military) and craving (Visual Analog Scale). Substance use and depression were also assessed.


Participants treated with N-acetylcysteine compared to placebo evidenced significant improvements in PTSD symptoms, craving, and depression (β values < -0.33; P values < .05). Substance use was low for both groups, and no significant between-group differences were observed. N-acetylcysteine was well tolerated, and retention was high.


This is the first randomised controlled trial to investigate N-acetylcysteine as a pharmacologic treatment for PTSD and SUD. Although preliminary, the findings provide initial support for the use of N-acetylcysteine in combination with psychotherapy among individuals with co-occurring PTSD and SUD.


Back, S.E., McCauley, J.L., Korte, K.J., Gros, D.F., Leavitt, V., Gray, K.M., Hamner. M.B., DeSantis, S.M., Malcolm, R., Brady, K.T. & Kalivas, P.W. (2016) A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders. The Journal of Clinical Psychiatry. 2016 Oct 11. doi: 10.4088/JCP.15m10239. [Epub ahead of print].


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