N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action
Open accessAbstract
There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.
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The clinical efficacy of NAC in tobacco use disorder may be explained by its effects on craving and reward, which are partly modulated by glutamate metabolism.
“The clinical efficacy of NAC in tobacco use disorder may be explained by its effects on craving and reward, which are in part modulated by glutamate metabolism.9”
From <i>N</i>-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study (2015) · cites this paper as [9]
NAC may reduce craving and reward behaviors in nicotine dependence, which are both modulated by glutamate.
“NAC may reduce craving and reward behaviors in nicotine dependence, which are both modulated by glutamate.9”
From <i>N</i>-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study (2015) · cites this paper as [9]
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Berk, M., Malhi, G. S., Gray, L. J., & Dean, O. M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.01.001 · Cited by 434 · see citing works
Self-citationPittenger, C., Bloch, M. H., & Williams, K. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.09.006 · Cited by 426 · see citing works
Maes, M., Fišar, Z., Medina, M., Scapagnini, G., Nowak, G., & Berk, M. (2012) · Inflammopharmacology · doi:10.1007/s10787-011-0111-7 · Cited by 325 · see citing works
Self-citationGray, K. M., Carpenter, M. J., Baker, N. L., DeSantis, S. M., Kryway, E., Hartwell, K. J., McRae-Clark, A. L., & Brady, K. T. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12010055 · Cited by 306 · see citing works
The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder
Wu, K., Hanna, G. L., Rosenberg, D. R., & Arnold, P. D. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.10.007 · Cited by 264 · see citing works
Firth, J., Teasdale, S. B., Allott, K., Siskind, D., Marx, W., Cotter, J., Veronese, N., Schuch, F., Smith, L., Solmi, M., et al. (2019) · World Psychiatry · doi:10.1002/wps.20672 · Cited by 214 · see citing works
Self-citationImaging glutamate in schizophrenia: review of findings and implications for drug discovery
Poels, E. M. P., Kegeles, L. S., Kantrowitz, J. T., Slifstein, M., Javitt, D. C., Lieberman, J. A., Abi-Dargham, A., & Girgis, R. R. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.136 · Cited by 205 · see citing works
Berk, M., Dean, O. M., Cotton, S. M., Jeavons, S., Tanious, M., Kohlmann, K., Hewitt, K., Moss, K., Allwang, C., Schapkaitz, I., et al. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13m08454 · Cited by 172 · see citing works
Self-citationAnti-inflammatory treatments for mood disorders: Systematic review and meta-analysis
Husain, M. I., Strawbridge, R., Stokes, P. R., & Young, A. H. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117725711 · Cited by 139 · see citing works
Minocycline: Therapeutic Potential in Psychiatry
Dean, O. M., Data-Franco, J., Giorlando, F., & Berk, M. (2012) · CNS Drugs · doi:10.2165/11632000-000000000-00000 · Cited by 131 · see citing works
Self-citationRole of the Astroglial Glutamate Exchanger xCT in Ventral Hippocampus in Resilience to Stress
Nasca, C., Bigio, B., Zelli, D., de Angelis, P., Lau, T., Okamoto, M., Soya, H., Ni, J., Brichta, L., Greengard, P., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.020 · Cited by 113 · see citing works
The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders
Bradlow, R. C. J., Berk, M., Kalivas, P. W., Back, S. E., & Kanaan, R. A. (2022) · CNS Drugs · doi:10.1007/s40263-022-00907-3 · Cited by 87 · see citing works
Self-citationGlycine transport inhibitors in the treatment of schizophrenia
Javitt, D. C. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25758-2_12 · Cited by 83 · see citing works
<i>N</i>-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study
Prado, E., Maes, M., Piccoli, L. G., Baracat, M., Barbosa, D. S., Franco, O., Dodd, S., Berk, M., & Vargas Nunes, S. O. (2015) · Redox Report · doi:10.1179/1351000215y.0000000004 · Cited by 69 · see citing works
Self-citationEffects of <scp>N</scp>‐acetyl cysteine on cognitive function in bipolar disorder
Dean, O. M., Bush, A. I., Copolov, D. L., Kohlmann, K., Jeavons, S., Schapkaitz, I., Anderson‐Hunt, M., & Berk, M. (2012) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2012.02392.x · Cited by 58 · see citing works
Self-citationA preliminary investigation on the efficacy of <i>N</i> -acetyl cysteine for mania or hypomania
Vieira da Silva Magalhães, P., Dean, O. M., Bush, A. I., Copolov, D. L., Malhi, G. S., Kohlmann, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., & Berk, M. (2013) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867413481631 · Cited by 58 · see citing works
Self-citationFrança, K., Kumar, A., Castillo, D., Jafferany, M., Hyczy da Costa Neto, M., Damevska, K., Wollina, U., & Lotti, T. (2019) · Dermatologic Therapy · doi:10.1111/dth.12622 · Cited by 51 · see citing works
Hadi, F., Kashefinejad, S., Kamalzadeh, L., Hoobehfekr, S., & Shalbafan, M. (2021) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-021-00534-6 · Cited by 36 · see citing works
Mitochondrial Dysfunction in Bipolar Disorder: Lessons from Brain Imaging and Molecular Markers
Minuzzi, L., Behr, G. A., Moreira, J. C. F., & Frey, B. N. (2011) · Revista Colombiana de Psiquiatría · doi:10.1016/s0034-7450(14)60201-8 · Cited by 7 · see citing works
- Authors
- Dean, O., Giorlando, F., & Berk, M.
- Affiliations
- Barwon Health (AU)
- ORCID
- Dean, Olivia
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2011-03
- Volume
- 36
- Issue
- 2
- Pages
- 78-86
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC3044191
- OpenAlex
- W2124107177
- Cited by
- 494
- References
- 85
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 30 · 2023: 25 · 2022: 31 · 2021: 28 · 2020: 35 · 2019: 34 · 2018: 43 · 2017: 41 · 2016: 23 · 2015: 41 · 2014: 32 · 2013: 42 · 2012: 31
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- N-acetylcysteine, mental illness, glutathione, glutamatergic pathways, neuroinflammation, addiction, compulsive disorders, schizophrenia, bipolar disorder, mechanism of action
- MeSH terms
- Acetylcysteine, Mental Disorders, Humans
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