Applications of N-Acetylcysteine (NAC) – From Addiction to Autism By Prof Berk

Professor Michael Berk is currently an NHMRC Senior Principal research Fellow and Alfred Deakin Chair of Psychiatry at Deakin University and Barwon Health, where he heads the IMPACT Strategic Research Centre. He holds an Honorary position at both Melbourne and Monash University and is a highly cited researcher with over 800 published papers predominantly in mood disorders. His major interests are in the discovery and implementation of novel therapies, and risk factors and prevention of psychiatric disorders.

Author Quotes

In addiction, you have a situation where glial glutamate uptake is via a transporter called Glutamate Transporter 1 (GLT1) and drug abuse down regulates this transporter. As a consequence, there is more Glutamate in the synaptic cleft, it overstimulates metabotropic glutamate receptor type 5 and NMDA receptors, increasing AMPA signalling and potentiating synaptic activity… NAC normalises this. Autism is a very heterogeneous disorder and what you call Autism may differ hugely and how you diagnose it may differ hugely. One of the things about OCD… is that it is one of the most placebo unresponsive condition we have in psychiatry. Anything that gets OCD better is real.”

Summary and Slides

Prof Michael Berk talks about the application of NAC in addiction, autism, OCD and traumatic brain injury.

NAC and Addiction

A randomized controlled trial (RCT) of NAC in cannabis dependent adolescents showed participants receiving NAC had more than twice the odds, compared with those receiving placebo, of having negative urine cannabinoid test results during treatment. (Gray et al., )

Summary of why NAC may work for addiction:

Glial glutamate uptake is by glial glutamate transporter 1 (GLT1)

After long-term drug use, glutamate uptake via GLT1 is downregulated

Glutamate more readily overflows the synaptic cleft to stimulate postsynaptic mGluR5 and NMDA receptors, increasing AMPA signaling, and potentiating the synaptic activity

N-acetylcysteine restores GLT1, thereby normalizing synaptic potentiation

NAC and Autism



A 12 week RCT of NAC in children with autism showed that NAC resulted in significant improvements on the Aberrant behavior checklist (ABC) irritability subscale and was well tolerated. (Hardan et al., )

NAC and OCD

A study by Afshar et al. randomized 48 patients with obsessive-compulsive disorder who failed to respond to a course of serotonin reuptake inhibitor treatment to a 12-week intervention period of N-acetylcysteine (up to 2400 mg/d) or placebo. 52.6% responded in the N-acetylcysteine group at the end of the study, which was significantly higher than 15% of the patients in the placebo group. The response was measured by Y-BOCS and CGI scale.

NAC and Traumatic Brain Injury

A double-blind RCT was conducted on soldiers in Iraq who had a mild traumatic brain injury from a significant ordnance blast. Using a 4g dose over 7 days, the study found that 86% of those receiving NAC within 24 hours had no sequelae in comparison to 42% who received a placebo. However, this is the first study of its kind and is yet to be replicated.

Take-home Points

N-Acetylcysteine (NAC) can cross the blood brain barrier

Studies of NAC in autism have reveal ed negative results on total aberrant behaviour checklist

Administration of NAC (within 24 hours) might be a possible future treatment for a variety of forms of trauma

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References:

Gray, K. M., et al., (2012). A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. American Journal of Psychiatry, 169(8), 805-812. Hardan, A. Y., et al., (2012). A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biological psychiatry, 71(11), 956-961. Afshar, H., et al., (2012). N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. Journal of clinical psychopharmacology, 32(6), 797-803. Hoffer, M. E., et al., (2013). Amelioration of acute sequelae of blast-induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo-controlled study. PloS one, 8(1), e54163.