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

Posted on March 3, 2017

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

NAC and Addiction

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.

A randomised 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 for 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 signalling, and potentiating synaptic activity
  • N-acetylcysteine restores GLT1, thereby normalising synaptic potentiation

NAC and Autism

Autism is a very heterogeneous disorder and what you call Autism may differ hugely and how you diagnose it may differ hugely.

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

NAC and OCD

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.

A study by Afshar et al. randomised 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 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 placebo. However, this is the first study of its kind and is yet to be replicated.

Want to learn more? Prof Berk on oxidative and inflammatory biomarkers in psychiatry.

NAC, Glutathione and oxidative stress.

NAC in Schizophrenia and Bipolar Disorder

References:

  1. 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.
  2. 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.
  3. 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.
  4. 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.