N-Acetylcysteine (NAC), a powerful anti-oxidant has become a well-researched nutritional supplement in today’s literature for its potent effect in treating patients with substance abuse disorders (SUDs).
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It has also, become popular and widely purchased to improve therapeutic strategies for COVID-19 treatment (Wong et al., 2021), which at one point, couldn’t be purchased anywhere!
Mind you, though, we’re not here to talk about that.
What we want to talk about in this article is what N-Acetylcysteine actually is, and some of the evidence available on using NAC to assist with various substance use disorders, and manage our withdrawal symptoms.
What is N-Acetylcysteine?
N-Acetylcysteine (NAC) is a precursor of the amino acid L-cysteine, and acts as a strong free radical scavenger, making it a potent anti-oxidant.
This anti-oxidant potential is important for many things, including improving the function of our immune system, and boosting various detoxification pathways (Dröge & Breitkreutz, 2000), something we may need to boost in alcohol or drug sobriety.
On top of this, glutathione also helps increase oxygen delivery to tissues, boosts the function of our mitochondrial powerhouses found in our cells, and improves blood flow to the liver to further assist in detoxification processes (Ershad et al., 2021).
In terms of clinical treatment, N-Acetylcysteine has been used for over 30 years in situations of paracetamol overdose, and also more recently in the treatment of chronic obstructive pulmonary disease, cystic fibrosis, and contrast-induced nephropathy (Ooi et al., 2018).
In recent studies, NAC has been applied to conditions of oxidative stress and reduced anti-oxidant status, which is closely tied to psychiatric and psychiatric-related conditions, including substance abuse (Chang et al., 2021).
Is alcohol craving more of a major issue for you? Read this article on crushing alcohol cravings with L-Glutamine.
Core Mechanisms of Action for N-Acetylcysteine
Increasing glutathione production – which assists in immune regulation and restoring anti-oxidant balance commonly attributed to psychiatric, addictive conditions, and various substance use disorders (Ooi et al., 2018).
Restore dopamine neurotransmitter dysregulation – This includes improving dopamine receptor binding and an increase in neuron survival, which helps to correct and re-balance the body’s natural risk and reward behavioural system (Monti et al., 2016).
Restore glutamate neurotransmitter dysregulation – Glutamate imbalance is quite common in alcohol and drug addiction, and symptoms usually present as anxiety, irritation, and jitteriness. NAC helps to re-balance this, and conversely, increase our levels of Gamma-Aminobutyric Acid, our calming, inhibitory neurotransmitter (Gorelick, 2019).
Assists in the modulation of inflammatory pathways – Including the reduction of elevated levels of various cytokines including interleukin-6, C-reactive protein, and tumour necrosis factor-alpha. This reduction of inflammatory pathways may also ameliorate oxidative stress implications, common in substance use disorders (Ooi et al., 2018).
N-Acetylcysteine Use in Treatment
Below are some suggested uses of N-Acetylcysteine as they apply to specific substance use disorders.
NAC and Cocaine Use Disorder Treatment
Doses of between 1,200 – 2,400 mg/day have reported outcomes of a reduction and frequency of cocaine cravings (Amen et al., 2010), and were more likely to remain abstinent for longer (LaRowe et al., 2013).
NAC and Methamphetamine Use Disorder Treatment
Doses of 1,200 mg/day have reported outcomes of a reduction in methamphetamine cravings during a crossover trial of 4 weeks, concluding it as an efficacious method in the treatment of methamphetamine dependency (Schmaal et al., 2011).
NAC and Cannabis Use Disorder Treatment
Doses of 2,400 mg/day have reported outcomes of a reduction in cravings and the amount of cannabis use and “hits” per day. More research is suggested for further understanding of efficacy (Gray et al., 2010).
NAC and Tobacco Use Disorder Treatment
Doses of between 1,200 – 3,600 mg/day have reported outcomes of fewer symptoms of nicotine dependence (Grant et al., 2013) and a reduction in cigarette usage, compared with the placebo group (Prado et al., 2015).
NAC and Alcohol Use Disorder Treatment
Doses of between 1,000 – 2,400 mg/day have reported outcomes that NAC may reduce symptoms of withdrawal, prevent alcohol toxicity and reduce oxidative stress that comes from excessive alcohol use (Ooi et al., 2018).
NAC and Other Psychiatric Uses
Due to NAC’s oxidative stress reducing and anti-inflammatory properties, it also serves as a great use for schizophrenia, bipolar, irritability, depression, and other various mood-related symptoms (Ooi et al., 2018).
N-Acetylcysteine (NAC) is an amazing and nutritional compound when It comes to managing our sobriety, and has been well studied across various substance use disorders.
Not only does it fix some of the neurotransmitters that may come out of balance during alcohol or drug addiction, but it’s also a potent anti-oxidant, and helps lower inflammation that may come from excessive substance use.
Personally, I found it extremely useful in managing alcohol withdrawal, but it has also shown effective in other addiction disorders including cocaine, methamphetamine, cannabis, and tobacco.
It has been shown effective in various SUDs including cocaine, methamphetamine, cannabis, tobacco, and alcohol; although in some instances more research is required.
Have you used NAC before? What were your experiences with it? Let us know in the comments!
- Amen, S. L., Piacentine, L. B., Ahmad, M. E., Li, S., Mantsch, J. R., Risinger, R. C., & Baker, D. A. (2010). Repeated N-acetyl cysteine reduces cocaine seeking in rodents and craving in cocaine-dependent humans. Neuropsychopharmacology, 36(4), 871-878. https://doi.org/10.1038/npp.2010.226
- Chang, C., Hsieh, P., Lee, H., Lo, C., Tam, K., & Loh, E. (2021). Effectiveness of N-acetylcysteine in treating clinical symptoms of substance abuse and dependence: A meta-analysis of randomized controlled trials. Clinical Psychopharmacology and Neuroscience, 19(2), 282-293. https://doi.org/10.9758/cpn.2021.19.2.282
- Dröge, W., & Breitkreutz, R. (2000). Glutathione and immune function. Proceedings of the Nutrition Society, 59(4), 595-600. https://doi.org/10.1017/s0029665100000847
- Ershad M, Naji A, Vearrier D. N Acetylcysteine. [Updated 2021 Jun 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537183/
- Gorelick, D. A. (2019). N-acetylcysteine in treatment of substance use disorders. Biological Psychiatry, 85(11), e59. https://doi.org/10.1016/j.biopsych.2018.11.018
- Grant, J. E., Odlaug, B. L., Chamberlain, S. R., Potenza, M. N., Schreiber, L. R., Donahue, C. B., & Kim, S. W. (2013). A randomized, placebo-controlled trial ofn-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers. The Journal of Clinical Psychiatry, 75(01), 39-45. https://doi.org/10.4088/jcp.13m08411
- Gray, K. M., Watson, N. L., Carpenter, M. J., & LaRowe, S. D. (2010). N-acetylcysteine (NAC) in young marijuana users: An open-label pilot study. The American Journal on Addictions, 19(2), 187-189. https://doi.org/10.1111/j.1521-0391.2009.00027.x
- LaRowe, S. D., Kalivas, P. W., Nicholas, J. S., Randall, P. K., Mardikian, P. N., & Malcolm, R. J. (2013). A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence. The American Journal on Addictions, 22(5), 443-452. https://doi.org/10.1111/j.1521-0391.2013.12034.x
- Mokhtari, V., Afsharian, P., Shahhoseini, M., Kalantar, S. M., & Moini, A. (2017). A Review on Various Uses of N-Acetyl Cysteine. Cell journal, 19(1), 11–17. https://doi.org/10.22074/cellj.2016.4872
- Monti, D. A., Zabrecky, G., Kremens, D., Liang, T., Wintering, N. A., Cai, J., Wei, X., Bazzan, A. J., Zhong, L., Bowen, B., Intenzo, C. M., Iacovitti, L., & Newberg, A. B. (2016). N-acetyl cysteine may support dopamine neurons in Parkinson’s disease: Preliminary clinical and cell line data. PLOS ONE, 11(6), e0157602. https://doi.org/10.1371/journal.pone.0157602
- Ooi, S. L., Green, R., & Pak, S. C. (2018). N-acetylcysteine for the treatment of psychiatric disorders: A review of current evidence. BioMed Research International, 2018, 1-8. https://doi.org/10.1155/2018/2469486
- Prado, E., Maes, M., Piccoli, L. G., Baracat, M., Barbosa, D. S., Franco, O., Dodd, S., Berk, M., & Vargas Nunes, S. O. (2015). N-acetylcysteine for therapy-resistant tobacco use disorder: A pilot study. Redox Report, 20(5), 215-222. https://doi.org/10.1179/1351000215y.0000000004
- Schmaal, L., Berk, L., Hulstijn, K. P., Cousijn, J., Wiers, R. W., & Van den Brink, W. (2011). Efficacy of N-acetylcysteine in the treatment of nicotine dependence: A double-blind placebo-controlled pilot study. European Addiction Research, 17(4), 211-216. https://doi.org/10.1159/000327682
- Wong, K. K., Lee, S. W., & Kua, K. P. (2021). N-acetylcysteine as adjuvant therapy for COVID-19 – A perspective on the current state of the evidence. Journal of Inflammation Research, 14, 2993-3013. https://doi.org/10.2147/jir.s306849
Former drinker, Nutritionist, Biohacking enthusiast, self-experimenter, research fanatic, and self-taught writer, Stephen immerses himself deep into the literature of human optimisation and better understand the nature of addiction. His goal is to help people take control of their addiction, reset their cravings, unscramble their broken brain circuitry and use actionable strategies that work ten times better than anything else.