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image of The Emerging Role of N-Acetylcysteine in Psychiatry: A Narrative Review of Available Data

Abstract

N-acetylcysteine (NAC), a cysteine derivative with a reactive thiol group, possesses antioxidant and anti-inflammatory properties. Its redox activity plays a central role in scavenging reactive oxygen and nitrogen species and modulating cellular signaling pathways. Recent research highlights its potential role in psychiatric disorders through the modulation of oxidative stress and inflammatory pathways. This narrative review examines the efficacy of NAC in treating psychiatric conditions, including mood disorders, schizophrenia, anxiety disorders, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), substance use disorders (SUDs), and neurodevelopmental disorders. A comprehensive search of PubMed, Scopus, Embase, PsycINFO, and Google Scholar databases was conducted for studies published between March 1, 2007, and December 30, 2024. The search utilized keywords related to NAC and psychiatric disorders. Data were critically analyzed to evaluate NAC’s therapeutic potential. Preclinical studies demonstrate NAC’s benefits in reducing oxidative stress, inflammation, and modulating neurotransmitter systems. Animal models of depression, schizophrenia, and OCD show symptom reduction through glutamatergic and antioxidant mechanisms. Clinical trials reveal NAC’s efficacy as an adjunct in treating major depressive disorder, bipolar disorder, and schizophrenia, particularly for negative and cognitive symptoms. Evidence for anxiety disorders, PTSD, and OCD is limited but suggests anxiolytic and anti-obsessive effects. In SUDs, NAC shows promise in reducing cravings and substance-seeking behavior, while preliminary findings in autism suggest improvements in irritability and hyperactivity. NAC exhibits potential as an adjunctive treatment for various psychiatric disorders due to its safety profile, low cost, and broad mechanisms of action. However, clinical results are mixed, highlighting the need for larger, well-designed trials to confirm its efficacy and define optimal dosing strategies.

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2025-09-23
2025-11-05
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References

  1. Pei Y. Liu H. Yang Y. Yang Y. Jiao Y. Tay F.R. Chen J. Biological activities and potential oral applications of N-Acetylcysteine: Progress and prospects. Oxid. Med. Cell. Longev. 2018 2018 1 2835787 10.1155/2018/2835787 29849877
    [Google Scholar]
  2. Bains R. Bains V. The antioxidant master glutathione and periodontal health. Dent. Res. J. 2015 12 5 389 405 10.4103/1735‑3327.166169 26604952
    [Google Scholar]
  3. Aldini G. Altomare A. Baron G. Vistoli G. Carini M. Borsani L. Sergio F. N-Acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radic. Res. 2018 52 7 751 762 10.1080/10715762.2018.1468564 29742938
    [Google Scholar]
  4. Tenório M.C.S. Graciliano N.G. Moura F.A. Oliveira A.C.M. Goulart M.O.F. N-Acetylcysteine (NAC): Impacts on human health. Antioxidants 2021 10 6 967 10.3390/antiox10060967 34208683
    [Google Scholar]
  5. Vašková J. Kočan L. Vaško L. Perjési P. Glutathione-related enzymes and proteins: A review. Molecules 2023 28 3 1447 10.3390/molecules28031447 36771108
    [Google Scholar]
  6. Elbini Dhouib I. Jallouli M. Annabi A. Gharbi N. Elfazaa S. Lasram M.M. A minireview on N -acetylcysteine: An old drug with new approaches. Life Sci. 2016 151 359 363 10.1016/j.lfs.2016.03.003 26946308
    [Google Scholar]
  7. Pedre B. Barayeu U. Ezeriņa D. Dick T.P. The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacol. Ther. 2021 228 107916 10.1016/j.pharmthera.2021.107916 34171332
    [Google Scholar]
  8. Livingstone C.R. Andrews M.A. Jenkins S.M. Marriott C. Model systems for the evaluation of mucolytic drugs: Acetylcysteine and S-carboxymethylcysteine. J. Pharm. Pharmacol. 1990 42 2 73 78 10.1111/j.2042‑7158.1990.tb05357.x 1972405
    [Google Scholar]
  9. Samuni Y. Goldstein S. Dean O.M. Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim. Biophys. Acta, Gen. Subj. 2013 1830 8 4117 4129 10.1016/j.bbagen.2013.04.016 23618697
    [Google Scholar]
  10. Zafarullah M. Li W.Q. Sylvester J. Ahmad M. Molecular mechanisms of N -acetylcysteine actions. Cell. Mol. Life Sci. 2003 60 1 6 20 10.1007/s000180300001 12613655
    [Google Scholar]
  11. Redondo P. Jimenez E. Perez A. García-Foncillas J. N -Acetylcysteine downregulates vascular endothelial growth factor production by human keratinocytes in vitro. Arch. Dermatol. Res. 2000 292 12 621 628 10.1007/s004030000187 11214823
    [Google Scholar]
  12. De Flora S. Izzotti A. D’Agostini F. Balansky R.M. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis 2001 22 7 999 1013 10.1093/carcin/22.7.999 11408342
    [Google Scholar]
  13. Palacio J.R. Markert U.R. Martínez P. Anti-inflammatory properties of N-acetylcysteine on lipopolysaccharide-activated macrophages. Inflamm. Res. 2011 60 7 695 704 10.1007/s00011‑011‑0323‑8 21424515
    [Google Scholar]
  14. Douiev L. Soiferman D. Alban C. Saada A. The effects of ascorbate, N-acetylcysteine, and resveratrol on fibroblasts from patients with mitochondrial disorders. J. Clin. Med. 2016 6 1 1 10.3390/jcm6010001 28025489
    [Google Scholar]
  15. Rossignol D.A. The use of N-Acetylcysteine as a chelator for metal toxicity. The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine. Frye R.E. Berk M. Singapore Springer Singapore 2019 169 179 10.1007/978‑981‑10‑5311‑5_10
    [Google Scholar]
  16. Tardiolo G. Bramanti P. Mazzon E. Overview on the effects of N-Acetylcysteine in neurodegenerative diseases. Molecules 2018 23 12 3305 10.3390/molecules23123305 30551603
    [Google Scholar]
  17. Reissner K.J. Kalivas P.W. Using glutamate homeostasis as a target for treating addictive disorders. Behav. Pharmacol. 2010 21 5-6 514 522 10.1097/FBP.0b013e32833d41b2 20634691
    [Google Scholar]
  18. Bradlow R.C.J. Berk M. Kalivas P.W. Back S.E. Kanaan R.A. The potential of N-Acetyl-L-Cysteine (NAC) in the treatment of psychiatric disorders. CNS Drugs 2022 36 5 451 482 10.1007/s40263‑022‑00907‑3 35316513
    [Google Scholar]
  19. Dantzer R. Cytokine-induced sickness behavior: Where do we stand? Brain Behav. Immun. 2001 15 1 7 24 10.1006/brbi.2000.0613 11259077
    [Google Scholar]
  20. Dean O. Giorlando F. Berk M. N-acetylcysteine in psychiatry: Current therapeutic evidence and potential mechanisms of action. J. Psychiatry Neurosci. 2011 36 2 78 86 10.1503/jpn.100057 21118657
    [Google Scholar]
  21. Smaga I. Frankowska M. Filip M. N-acetylcysteine in substance use disorder: A lesson from preclinical and clinical research. Pharmacol. Rep. 2021 73 5 1205 1219 10.1007/s43440‑021‑00283‑7 34091880
    [Google Scholar]
  22. Rowland T.A. Marwaha S. Epidemiology and risk factors for bipolar disorder. Ther. Adv. Psychopharmacol. 2018 8 9 251 269 10.1177/2045125318769235 30181867
    [Google Scholar]
  23. Bains N. Abdijadid S. Major depressive disorder. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  24. Casacalenda N. Perry J.C. Looper K. Remission in major depressive disorder: A comparison of pharmacotherapy, psychotherapy, and control conditions. Am. J. Psychiatry 2002 159 8 1354 1360 10.1176/appi.ajp.159.8.1354 12153828
    [Google Scholar]
  25. Pinto J.V. Saraf G. Kozicky J. Beaulieu S. Sharma V. Parikh S.V. Cervantes P. Daigneault A. Walji N. Kauer-Sant’Anna M. Yatham L.N. Remission and recurrence in bipolar disorder: The data from health outcomes and patient evaluations in bipolar disorder (HOPE-BD) study. J. Affect. Disord. 2020 268 150 157 10.1016/j.jad.2020.03.018 32174473
    [Google Scholar]
  26. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Washington, DC American Psychiatric Association Publishing 2022 10.1176/appi.books.9780890425787
    [Google Scholar]
  27. Miller A.H. Maletic V. Raison C.L. Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biol. Psychiatry 2009 65 9 732 741 10.1016/j.biopsych.2008.11.029 19150053
    [Google Scholar]
  28. Ferreira F.R. Biojone C. Joca S.R.L. Guimarães F.S. Antidepressant-like effects of N-acetyl-L-cysteine in rats. Behav. Pharmacol. 2008 19 7 747 750 10.1097/FBP.0b013e3283123c98 18797252
    [Google Scholar]
  29. Arent C.O. Réus G.Z. Abelaira H.M. Ribeiro K.F. Steckert A.V. Mina F. Dal-Pizzol F. Quevedo J. Synergist effects of n-acetylcysteine and deferoxamine treatment on behavioral and oxidative parameters induced by chronic mild stress in rats. Neurochem. Int. 2012 61 7 1072 1080 10.1016/j.neuint.2012.07.024 22898295
    [Google Scholar]
  30. Réus G.Z. Maciel A.L. Abelaira H.M. de Moura A.B. de Souza T.G. dos Santos T.R. Darabas A.C. Parzianello M. Matos D. Abatti M. Vieira A.C. Fucillini V. Michels M. Dal-Pizzol F. Quevedo J. ω-3 and folic acid act against depressive-like behavior and oxidative damage in the brain of rats subjected to early- or late-life stress. Nutrition 2018 53 120 133 10.1016/j.nut.2018.03.006 29783176
    [Google Scholar]
  31. Berk M. Dean O.M. Cotton S.M. Jeavons S. Tanious M. Kohlmann K. Hewitt K. Moss K. Allwang C. Schapkaitz I. Robbins J. Cobb H. Ng F. Dodd S. Bush A.I. Malhi G.S. The efficacy of adjunctive N-acetylcysteine in major depressive disorder: A double-blind, randomized, placebo-controlled trial. J. Clin. Psychiatry 2014 75 6 628 636 10.4088/JCP.13m08454 25004186
    [Google Scholar]
  32. Hasebe K. Gray L. Bortolasci C. Panizzutti B. Mohebbi M. Kidnapillai S. Spolding B. Walder K. Berk M. Malhi G. Dodd S. Dean O.M. Adjunctive N -acetylcysteine in depression: Exploration of interleukin-6, C-reactive protein and brain-derived neurotrophic factor. Acta Neuropsychiatr. 2017 29 6 337 346 10.1017/neu.2017.2 28318471
    [Google Scholar]
  33. Porcu M. Urbano M.R. Verri W.A. Jr Barbosa D.S. Baracat M. Vargas H.O. Machado R.C.B.R. Pescim R.R. Nunes S.O.V. Effects of adjunctive N-acetylcysteine on depressive symptoms: Modulation by baseline high-sensitivity C-reactive protein. Psychiatry Res. 2018 263 268 274 10.1016/j.psychres.2018.02.056 29605103
    [Google Scholar]
  34. Tomko R.L. Gilmore A.K. Gray K.M. The role of depressive symptoms in treatment of adolescent cannabis use disorder with N-Acetylcysteine. Addict. Behav. 2018 85 26 30 10.1016/j.addbeh.2018.05.014 29803870
    [Google Scholar]
  35. Kishi T. Miyake N. Okuya M. Sakuma K. Iwata N. N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: A systematic review and meta-analysis of double-blind, randomized placebo-controlled trials. Psychopharmacology 2020 237 11 3481 3487 10.1007/s00213‑020‑05629‑2 32767039
    [Google Scholar]
  36. Geddes J.R. Miklowitz D.J. Treatment of bipolar disorder. Lancet 2013 381 9878 1672 1682 10.1016/S0140‑6736(13)60857‑0 23663953
    [Google Scholar]
  37. Lima D.D. Cyrino L.A.R. Ferreira G.K. Magro D.D.D. Calegari C.R. Cabral H. Cavichioli N. Ramos S.A. Ullmann O.M. Mayer Y. Pscheidt L.C. Schramm M.A. Tomasi M.C. Stammerjohann F.L.S. Delmonego L. Packer M.H. Fiamoncini H. Neuroinflammation and neuroprogression produced by oxidative stress in euthymic bipolar patients with different onset disease times. Sci. Rep. 2022 12 1 16742 10.1038/s41598‑022‑21170‑y 36202963
    [Google Scholar]
  38. Nery F.G. Li W. DelBello M.P. Welge J.A. N-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials. Bipolar Disord. 2021 23 7 707 714 10.1111/bdi.13039 33354859
    [Google Scholar]
  39. Berk M. Copolov D.L. Dean O. Lu K. Jeavons S. Schapkaitz I. Anderson-Hunt M. Bush A.I. N-acetyl cysteine for depressive symptoms in bipolar disorder-a double-blind randomized placebo-controlled trial. Biol. Psychiatry 2008 64 6 468 475 10.1016/j.biopsych.2008.04.022 18534556
    [Google Scholar]
  40. Berk M. Dean O. Cotton S.M. Gama C.S. Kapczinski F. Fernandes B.S. Kohlmann K. Jeavons S. Hewitt K. Allwang C. Cobb H. Bush A.I. Schapkaitz I. Dodd S. Malhi G.S. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: An open label trial. J. Affect. Disord. 2011 135 1-3 389 394 10.1016/j.jad.2011.06.005 21719110
    [Google Scholar]
  41. 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. A preliminary investigation on the efficacy of N -acetyl cysteine for mania or hypomania. Aust. N. Z. J. Psychiatry 2013 47 6 564 568 10.1177/0004867413481631 23493756
    [Google Scholar]
  42. Waterdrinker A. Berk M. Venugopal K. Rapado-Castro M. Turner A. Dean O.M. Effects of N-Acetyl cysteine on suicidal ideation in bipolar depression. J. Clin. Psychiatry 2015 76 5 665 10.4088/JCP.14l09378 26035204
    [Google Scholar]
  43. Bauer I.E. Green C. Colpo G.D. Teixeira A.L. Selvaraj S. Durkin K. Zunta-Soares G.B. Soares J.C. A double-blind, randomized, placebo-controlled study of Aspirin and N-Acetylcysteine as adjunctive treatments for bipolar depression. J. Clin. Psychiatry 2018 80 1 18m12200 10.4088/JCP.18m12200 30549489
    [Google Scholar]
  44. Ellegaard P.K. Licht R.W. Nielsen R.E. Dean O.M. Berk M. Poulsen H.E. Mohebbi M. Nielsen C.T. The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study. J. Affect. Disord. 2019 245 1043 1051 10.1016/j.jad.2018.10.083 30699846
    [Google Scholar]
  45. Dean O.M. Bush A.I. Copolov D.L. Kohlmann K. Jeavons S. Schapkaitz I. Anderson-Hunt M. Berk M. Effects of N -acetyl cysteine on cognitive function in bipolar disorder. Psychiatry Clin. Neurosci. 2012 66 6 514 517 10.1111/j.1440‑1819.2012.02392.x 23066769
    [Google Scholar]
  46. Pittas S. Theodoridis X. Haidich A.B. Bozikas P.V. Papazisis G. The effect of N-acetylcysteine on bipolar depression: A systematic review and meta-analysis of randomized controlled trials. Psychopharmacology 2021 238 7 1729 1736 10.1007/s00213‑021‑05789‑9 33641060
    [Google Scholar]
  47. Lally J. MacCabe J.H. Antipsychotic medication in schizophrenia: A review. Br. Med. Bull. 2015 114 1 169 179 10.1093/bmb/ldv017 25957394
    [Google Scholar]
  48. Howes O. Fusar-Poli P. Osugo M. Treating negative symptoms of schizophrenia: Current approaches and future perspectives. Br. J. Psychiatry 2023 223 1 332 335 10.1192/bjp.2023.57 37272623
    [Google Scholar]
  49. Correll C.U. Schooler N.R. Negative symptoms in schizophrenia: A review and clinical guide for recognition, assessment, and treatment. Neuropsychiatr. Dis. Treat. 2020 16 519 534 10.2147/NDT.S225643 32110026
    [Google Scholar]
  50. Rapado-Castro M. Dodd S. Bush A.I. Malhi G.S. Skvarc D.R. On Z.X. Berk M. Dean O.M. Cognitive effects of adjunctive N -acetyl cysteine in psychosis. Psychol. Med. 2017 47 5 866 876 10.1017/S0033291716002932 27894373
    [Google Scholar]
  51. Berk M. Copolov D. Dean O. Lu K. Jeavons S. Schapkaitz I. Anderson-Hunt M. Judd F. Katz F. Katz P. Ording-Jespersen S. Little J. Conus P. Cuenod M. Do K.Q. Bush A.I. N-acetyl cysteine as a glutathione precursor for schizophrenia-a double-blind, randomized, placebo-controlled trial. Biol. Psychiatry 2008 64 5 361 368 10.1016/j.biopsych.2008.03.004 18436195
    [Google Scholar]
  52. Farokhnia M. Azarkolah A. Adinehfar F. Khodaie-Ardakani M.R. Hosseini S.M.R. Yekehtaz H. Tabrizi M. Rezaei F. Salehi B. Sadeghi S.M.H. Moghadam M. Gharibi F. Mirshafiee O. Akhondzadeh S. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: A randomized, double-blind, placebo-controlled study. Clin. Neuropharmacol. 2013 36 6 185 192 10.1097/WNF.0000000000000001 24201233
    [Google Scholar]
  53. Bowie C.R. Harvey P.D. Cognitive deficits and functional outcome in schizophrenia. Neuropsychiatr. Dis. Treat. 2006 2 4 531 536 10.2147/nedt.2006.2.4.531 19412501
    [Google Scholar]
  54. Retsa C. Knebel J.F. Geiser E. Ferrari C. Jenni R. Fournier M. Alameda L. Baumann P.S. Clarke S. Conus P. Do K.Q. Murray M.M. Treatment in early psychosis with N-acetyl-cysteine for 6 months improves low-level auditory processing: Pilot study. Schizophr. Res. 2018 191 80 86 10.1016/j.schres.2017.07.008 28711476
    [Google Scholar]
  55. Conus P. Seidman L.J. Fournier M. Xin L. Cleusix M. Baumann P.S. Ferrari C. Cousins A. Alameda L. Gholam-Rezaee M. Golay P. Jenni R. Woo T.U.W. Keshavan M.S. Eap C.B. Wojcik J. Cuenod M. Buclin T. Gruetter R. Do K.Q. N-Acetylcysteine in a double-blind randomized placebo-controlled trial: Toward biomarker-guided treatment in early psychosis. Schizophr. Bull. 2018 44 2 317 327 10.1093/schbul/sbx093 29462456
    [Google Scholar]
  56. Lavoie S. Murray M.M. Deppen P. Knyazeva M.G. Berk M. Boulat O. Bovet P. Bush A.I. Conus P. Copolov D. Fornari E. Meuli R. Solida A. Vianin P. Cuénod M. Buclin T. Do K.Q. Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology 2008 33 9 2187 2199 10.1038/sj.npp.1301624 18004285
    [Google Scholar]
  57. Uzun Ö. Bolu A. Çelik C. Effect of N-acetylcysteine on clozapine-induced sialorrhea in schizophrenic patients: A case series. Int. Clin. Psychopharmacol. 2020 35 4 229 231 10.1097/YIC.0000000000000297 31743234
    [Google Scholar]
  58. Neill E. Rossell S.L. Yolland C. Meyer D. Galletly C. Harris A. Siskind D. Berk M. Bozaoglu K. Dark F. Dean O.M. Francis P.S. Liu D. Phillipou A. Sarris J. Castle D.J. N -Acetylcysteine (NAC) in schizophrenia resistant to clozapine: A double-blind, randomized, placebo-controlled trial targeting negative symptoms. Schizophr. Bull. 2022 48 6 1263 1272 10.1093/schbul/sbac065 35857752
    [Google Scholar]
  59. Kessler R.C. Petukhova M. Sampson N.A. Zaslavsky A.M. Wittchen H.U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int. J. Methods Psychiatr. Res. 2012 21 3 169 184 10.1002/mpr.1359 22865617
    [Google Scholar]
  60. Locke A.B. Kirst N. Shultz C.G. Diagnosis and management of generalized anxiety disorder and panic disorder in adults. Am. Fam. Physician 2015 91 9 617 624 25955736
    [Google Scholar]
  61. Mocelin R. Herrmann A.P. Marcon M. Rambo C.L. Rohden A. Bevilaqua F. de Abreu M.S. Zanatta L. Elisabetsky E. Barcellos L.J.G. Lara D.R. Piato A.L. N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish. Pharmacol. Biochem. Behav. 2015 139 Pt B 121 126 10.1016/j.pbb.2015.08.006 26261019
    [Google Scholar]
  62. Santos P. Herrmann A.P. Benvenutti R. Noetzold G. Giongo F. Gama C.S. Piato A.L. Elisabetsky E. Anxiolytic properties of N -acetylcysteine in mice. Behav. Brain Res. 2017 317 461 469 10.1016/j.bbr.2016.10.010 27725170
    [Google Scholar]
  63. Lehmann M.L. Weigel T.K. Poffenberger C.N. Herkenham M. The behavioral sequelae of social defeat require microglia and are driven by oxidative stress in mice. J. Neurosci. 2019 39 28 5594 5605 10.1523/JNEUROSCI.0184‑19.2019 31085604
    [Google Scholar]
  64. Vukovic R. Kumburovic I. Joksimovic Jovic J. Jovicic N. Katanic Stankovic J.S. Mihailovic V. Djuric M. Velickovic S. Arnaut A. Selakovic D. Rosic G. N-Acetylcysteine protects against the anxiogenic response to Cisplatin in rats. Biomolecules 2019 9 12 892 10.3390/biom9120892 31861240
    [Google Scholar]
  65. Kitamura Y. Ushio S. Sumiyoshi Y. Wada Y. Miyazaki I. Asanuma M. Sendo T. N-Acetylcysteine attenuates the anxiety-like behavior and spatial cognition impairment induced by Doxorubicin and Cyclophosphamide combination treatment in rats. Pharmacology 2021 106 5-6 286 293 10.1159/000512117 33352577
    [Google Scholar]
  66. Aslanlar D.A. Vişneci E.F. Oz M. Nurullahoglu Atalik K.E. N-acetylcysteine ameliorates chemotherapy-induced impaired anxiety and depression-like behaviors by regulating inflammation, oxidative and cholinergic status, and BDNF release. Behav. Brain Res. 2024 458 114740 10.1016/j.bbr.2023.114740 37926333
    [Google Scholar]
  67. Strawn J.R. Saldaña S.N. Treatment with adjunctive N-acetylcysteine in an adolescent with selective serotonin reuptake inhibitor-resistant anxiety. J. Child Adolesc. Psychopharmacol. 2012 22 6 472 473 10.1089/cap.2012.0066 23234593
    [Google Scholar]
  68. Khalatbari Mohseni G. Hosseini S.A. Majdinasab N. Cheraghian B. Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis. Neuropsychopharmacol. Rep. 2023 43 3 382 390 10.1002/npr2.12360 37386885
    [Google Scholar]
  69. 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. A double-blind, randomized, controlled pilot trial of N-Acetylcysteine in veterans with posttraumatic stress disorder and substance use disorders. J. Clin. Psychiatry 2016 77 11 e1439 e1446 10.4088/JCP.15m10239 27736051
    [Google Scholar]
  70. Kanaan R.A. Oliver G. Dharan A. Sendi S. Maier A. Mohebbi M. Ng C. Back S.E. Kalivas P. Berk M. A multi-centre, double-blind, 12-week, randomized, placebo- controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD. Psychiatry Res. 2023 327 115398 10.1016/j.psychres.2023.115398 37540942
    [Google Scholar]
  71. Baumgarten H.G. Grozdanovic Z. Role of serotonin in obsessive-compulsive disorder. Br. J. Psychiatry 1998 173 S35 13 20 10.1192/S0007125000297857 9829022
    [Google Scholar]
  72. Calzà J. Gürsel D.A. Schmitz-Koep B. Bremer B. Reinholz L. Berberich G. Koch K. Altered cortico–striatal functional connectivity during resting state in Obsessive–Compulsive Disorder. Front. Psychiatry 2019 10 319 10.3389/fpsyt.2019.00319 31133898
    [Google Scholar]
  73. Marazziti D. Massa L. Carbone M.G. Palermo S. Arone A. D’Angelo G. Schulz Bizzozzero Crivelli N. Gurrieri R. Perrone P. Palagini L. Dell’Osso L. Silent infections are not so silent: The emerging role of combined infections, inflammation, and vitamin levels in OCD. Clin. Neuropsychiatry 2024 21 1 7 21 10.36131/cnfioritieditore20240101 38559435
    [Google Scholar]
  74. Egashira N. Shirakawa A. Abe M. Niki T. Mishima K. Iwasaki K. Oishi R. Fujiwara M. N-acetyl-L-cysteine inhibits marble-burying behavior in mice. J. Pharmacol. Sci. 2012 119 1 97 101 10.1254/jphs.11228SC 22510519
    [Google Scholar]
  75. Allen E.M. Hughes E.F. Anderson C.J. Woehrle N.S. N-acetylcysteine blocks serotonin 1B agonist-induced OCD-related behavior in mice. Behav. Neurosci. 2018 132 4 258 268 10.1037/bne0000251 29985009
    [Google Scholar]
  76. Li F. Welling M.C. Johnson J.A. Coughlin C. Mulqueen J. Jakubovski E. Coury S. Landeros-Weisenberger A. Bloch M.H. N-Acetylcysteine for pediatric Obsessive-Compulsive Disorder: A small pilot study. J. Child Adolesc. Psychopharmacol. 2020 30 1 32 37 10.1089/cap.2019.0041 31800306
    [Google Scholar]
  77. Sarris J. Oliver G. Camfield D.A. Dean O.M. Dowling N. Smith D.J. Murphy J. Menon R. Berk M. Blair-West S. Ng C.H. N-acetyl cysteine (NAC) in the treatment of Obsessive-Compulsive Disorder: A 16-week, double-blind, randomised, placebo-controlled study. CNS Drugs 2015 29 9 801 809 10.1007/s40263‑015‑0272‑9 26374743
    [Google Scholar]
  78. Afshar H. Roohafza H. Mohammad-Beigi H. Haghighi M. Jahangard L. Shokouh P. Sadeghi M. Hafezian H. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. J. Clin. Psychopharmacol. 2012 32 6 797 803 10.1097/JCP.0b013e318272677d 23131885
    [Google Scholar]
  79. Paydary K. Akamaloo A. Ahmadipour A. Pishgar F. Emamzadehfard S. Akhondzadeh S. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive- compulsive disorder: Randomized, double-blind, placebo- controlled trial. J. Clin. Pharm. Ther. 2016 41 2 214 219 10.1111/jcpt.12370 26931055
    [Google Scholar]
  80. Parli G.M. Gales M.A. Gales B.J. N-Acetylcysteine for Obsessive-Compulsive and related disorders in children and adolescents: A review. Ann. Pharmacother. 2023 57 7 847 854 10.1177/10600280221138092 36384314
    [Google Scholar]
  81. Ghanizadeh A. Derakhshan N. Berk M. N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial. Antiinflamm. Antiallergy Agents Med. Chem. 2013 12 3 223 228 10.2174/1871523011312030003 23651231
    [Google Scholar]
  82. Bloch M.H. Panza K.E. Grant J.E. Pittenger C. Leckman J.F. N-Acetylcysteine in the treatment of pediatric trichotillomania: A randomized, double-blind, placebo-controlled add-on trial. J. Am. Acad. Child Adolesc. Psychiatry 2013 52 3 231 240 10.1016/j.jaac.2012.12.020 23452680
    [Google Scholar]
  83. McPheeters M. O’Connor E.A. Riley S. Kennedy S.M. Voisin C. Kuznacic K. Coffey C.P. Edlund M.D. Bobashev G. Jonas D.E. Pharmacotherapy for alcohol use disorder: A systematic review and meta-analysis. JAMA 2023 330 17 1653 1665 10.1001/jama.2023.19761 37934220
    [Google Scholar]
  84. Schneider R. Jr Bandiera S. Souza D.G. Bellaver B. Caletti G. Quincozes-Santos A. Elisabetsky E. Gomez R. N-Acetylcysteine prevents alcohol related neuroinflammation in rats. Neurochem. Res. 2017 42 8 2135 2141 10.1007/s11064‑017‑2218‑8 28303497
    [Google Scholar]
  85. Lebourgeois S. Gonzalez-Marin M.C. Jeanblanc J. Naassila M. Vilpoux C. S14-3Effect of N-acetylcysteine on motivation, seeking and relapse to ethanol self-administration in alcohol dependent and non-dependent rats. Alcohol Alcohol. 2017 52 Suppl. 1 i4 i30 10.1093/alcalc/agx075.53
    [Google Scholar]
  86. Morley K.C. Peruch S. Adams C. Towers E. Tremonti C. Watt J. Jamshidi N. I Haber P.S. N acetylcysteine in the treatment of alcohol use disorder: A randomized, double-blind, placebo-controlled trial. Alcohol Alcohol. 2023 58 5 553 560 10.1093/alcalc/agad044 37465907
    [Google Scholar]
  87. Tiouririne N.A.D. Kalelioglu T. Seneviratne C. Wang X.Q. Safety and tolerability of topiramate and N-acetyl cysteine combination in individuals with alcohol use disorder: A 12 week, randomized, double-blind, pilot study. Alcohol Alcohol. 2024 59 2 agad082 10.1093/alcalc/agad082 38069498
    [Google Scholar]
  88. Kirkland A.E. Browning B.D. Green R. Liu H. Maralit A.M. Ferguson P.L. Meyerhoff D.J. Prisciandaro J.J. Miranda R. Jr Brady K.T. Tomko R.L. Gray K.M. Squeglia L.M. N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial. Neuropsychopharmacology 2023 48 8 1184 1193 10.1038/s41386‑023‑01553‑z 36878996
    [Google Scholar]
  89. Coppersmith V. Hudgins S. Stoltzfus J. Stankewicz H. The use of N-acetylcysteine in the prevention of hangover: A randomized trial. Sci. Rep. 2021 11 1 13397 10.1038/s41598‑021‑92676‑0 34183702
    [Google Scholar]
  90. Gray K.M. Watson N.L. Carpenter M.J. LaRowe S.D. N-acetylcysteine (NAC) in young marijuana users: An open-label pilot study. Am. J. Addict. 2010 19 2 187 189 10.1111/j.1521‑0391.2009.00027.x 20163391
    [Google Scholar]
  91. Gray K.M. Carpenter M.J. Baker N.L. DeSantis S.M. Kryway E. Hartwell K.J. McRae-Clark A.L. Brady K.T. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am. J. Psychiatry 2012 169 8 805 812 10.1176/appi.ajp.2012.12010055 22706327
    [Google Scholar]
  92. Gray K.M. Sonne S.C. McClure E.A. Ghitza U.E. Matthews A.G. McRae-Clark A.L. Carroll K.M. Potter J.S. Wiest K. Mooney L.J. Hasson A. Walsh S.L. Lofwall M.R. Babalonis S. Lindblad R.W. Sparenborg S. Wahle A. King J.S. Baker N.L. Tomko R.L. Haynes L.F. Vandrey R.G. Levin F.R. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017 177 249 257 10.1016/j.drugalcdep.2017.04.020 28623823
    [Google Scholar]
  93. Narasimha V.L. Shukla L. S Shyam R.P. Kandasamy A. Benegal V. Relative effectiveness of N-acetylcysteine and baclofen as anticraving agents in cannabis dependence - A retrospective study with telephonic follow-up. Indian J. Psychiatry 2019 61 3 228 231 10.4103/psychiatry.IndianJPsychiatry_16_19 31142898
    [Google Scholar]
  94. Reichel C.M. Moussawi K. Do P.H. Kalivas P.W. See R.E. Chronic N-acetylcysteine during abstinence or extinction after cocaine self-administration produces enduring reductions in drug seeking. J. Pharmacol. Exp. Ther. 2011 337 2 487 493 10.1124/jpet.111.179317 21303920
    [Google Scholar]
  95. Schmaal L. Goudriaan A.E. Joos L. Krüse A.M. Dom G. van den Brink W. Veltman D.J. Modafinil modulates resting-state functional network connectivity and cognitive control in alcohol-dependent patients. Biol. Psychiatry 2013 73 8 789 795 10.1016/j.biopsych.2012.12.025 23399373
    [Google Scholar]
  96. Amen D. Stubblefield M. Carmichael B. Thisted R. Brain SPECT findings and aggressiveness. Ann. Clin. Psychiatry 1996 8 3 129 137 10.3109/10401239609147750 8899131
    [Google Scholar]
  97. LaRowe S.D. Myrick H. Hedden S. Mardikian P. Saladin M. McRae A. Brady K. Kalivas P.W. Malcolm R. Is cocaine desire reduced by N-acetylcysteine? Am. J. Psychiatry 2007 164 7 1115 1117 10.1176/ajp.2007.164.7.1115 17606664
    [Google Scholar]
  98. Woodcock E.A. Lundahl L.H. Khatib D. Stanley J.A. Greenwald M.K. N -acetylcysteine reduces cocaine-seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine-dependent individuals. Addict. Biol. 2021 26 2 12900 10.1111/adb.12900 32212237
    [Google Scholar]
  99. Schulte M.H.J. Goudriaan A.E. Kaag A.M. Kooi D.P. van den Brink W. Wiers R.W. Schmaal L. The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial. J. Psychopharmacol. 2017 31 10 1377 1379 10.1177/0269881117730660 28922968
    [Google Scholar]
  100. Zhou W. Kalivas P.W. N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking. Biol. Psychiatry 2008 63 3 338 340 10.1016/j.biopsych.2007.06.008 17719565
    [Google Scholar]
  101. Wilson S.H. Sirianni J.M. Bridges K.H. Wolf B.J. Valente I.E. Scofield M.D. The impact of intraoperative N-acetylcysteine on opioid consumption following spine surgery: A randomized pilot trial. Pain Manag. 2023 13 10 593 602 10.2217/pmt‑2023‑0061 37877260
    [Google Scholar]
  102. Hashimoto K. Tsukada H. Nishiyama S. Fukumoto D. Kakiuchi T. Shimizu E. Iyo M. Protective effects of N-acetyl-L-cysteine on the reduction of dopamine transporters in the striatum of monkeys treated with methamphetamine. Neuropsychopharmacology 2004 29 11 2018 2023 10.1038/sj.npp.1300512 15199373
    [Google Scholar]
  103. Charntikov S. Pittenger S.T. Pudiak C.M. Bevins R.A. The effect of N-acetylcysteine or bupropion on methamphetamine self-administration and methamphetamine–triggered reinstatement of female rats. Neuropharmacology 2018 135 487 495 10.1016/j.neuropharm.2018.03.021 29604294
    [Google Scholar]
  104. Siemsen B.M. Reichel C.M. Leong K.C. Garcia-Keller C. Gipson C.D. Spencer S. McFaddin J.A. Hooker K.N. Kalivas P.W. Scofield M.D. Effects of methamphetamine self-administration and extinction on astrocyte structure and function in the nucleus accumbens core. Neuroscience 2019 406 528 541 10.1016/j.neuroscience.2019.03.040 30926546
    [Google Scholar]
  105. Grant J.E. Odlaug B.L. Kim S.W. A double-blind, placebo-controlled study of N-acetyl cysteine plus naltrexone for methamphetamine dependence. Eur. Neuropsychopharmacol. 2010 20 11 823 828 10.1016/j.euroneuro.2010.06.018 20655182
    [Google Scholar]
  106. Mousavi S.G. Sharbafchi M.R. Salehi M. Peykanpour M. Karimian Sichani N. Maracy M. The efficacy of N-acetylcysteine in the treatment of methamphetamine dependence: A double-blind controlled, crossover study. Arch. Iran Med. 2015 18 1 28 33 25556383
    [Google Scholar]
  107. McKetin R. Dean O.M. Turner A. Kelly P.J. Quinn B. Lubman D.I. Dietze P. Carter G. Higgs P. Sinclair B. Reid D. Baker A.L. Manning V. Pas N. Thomas T. Bathish R. Raftery D.K. Wrobel A. Saunders L. Arunogiri S. Cordaro F. Hill H. Hall S. Clare P.J. Mohebbi M. Berk M. N-acetylcysteine (NAC) for methamphetamine dependence: A randomised controlled trial. EClinicalMedicine 2021 38 101005 10.1016/j.eclinm.2021.101005 34308314
    [Google Scholar]
  108. Sacks J.J. Nelson D.E. Smoking and injuries: An overview. Prev. Med. 1994 23 4 515 520 10.1006/pmed.1994.1070 7971880
    [Google Scholar]
  109. Goenaga J. Powell G.L. Leyrer-Jackson J.M. Piña J. Phan S. Prakapenka A.V. Koebele S.V. Namba M.D. McClure E.A. Bimonte-Nelson H.A. Gipson C.D. N -acetylcysteine yields sex-specific efficacy for cue-induced reinstatement of nicotine seeking. Addict. Biol. 2020 25 1 12711 10.1111/adb.12711 30734439
    [Google Scholar]
  110. Prado E. Maes M. Piccoli L.G. Baracat M. Barbosa D.S. Franco O. Dodd S. Berk M. Vargas Nunes S.O. N -acetylcysteine for therapy-resistant tobacco use disorder: A pilot study. Redox Rep. 2015 20 5 215 222 10.1179/1351000215Y.0000000004 25729878
    [Google Scholar]
  111. ` MachadoR.C.B.R. VargasH.O. BaracatM.M. UrbanoM.R. VerriW.A. PorcuM. NunesS.O.V. N-acetylcysteine as an adjunctive treatment for smoking cessation: A randomized clinical trial. Rev. Bras. Psiquiatr. 2020 42 5 519 526 10.1590/1516‑4446‑2019‑0753
    [Google Scholar]
  112. Harlivasari A.D. Susanto A.D. Taufik F.F. Ginting T.T. The role of twice-daily N-Acetylcysteine (NAC) 2400 Mg in smoking cessation: A randomized, placebo-controlled trial in Indonesia. Cureus 2024 16 2 54322 10.7759/cureus.54322 38500894
    [Google Scholar]
  113. Durieux A.M.S. Horder J. Mendez M.A. Egerton A. Williams S.C.R. Wilson C.E. Spain D. Murphy C. Robertson D. Barker G.J. Murphy D.G. McAlonan G.M. Cortical and subcortical glutathione levels in adults with autism spectrum disorder. Autism Res. 2016 9 4 429 435 10.1002/aur.1522 26290215
    [Google Scholar]
  114. Liu X. Lin J. Zhang H. Khan N.U. Zhang J. Tang X. Cao X. Shen L. Oxidative stress in Autism Spectrum Disorder—Current progress of mechanisms and biomarkers. Front. Psychiatry 2022 13 813304 10.3389/fpsyt.2022.813304 35299821
    [Google Scholar]
  115. Hardan A.Y. Fung L.K. Libove R.A. Obukhanych T.V. Nair S. Herzenberg L.A. Frazier T.W. Tirouvanziam R. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol. Psychiatry 2012 71 11 956 961 10.1016/j.biopsych.2012.01.014 22342106
    [Google Scholar]
  116. Ghanizadeh A. Moghimi-Sarani E. A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders. BMC Psychiatry 2013 13 1 196 10.1186/1471‑244X‑13‑196 23886027
    [Google Scholar]
  117. Nikoo M. Radnia H. Farokhnia M. Mohammadi M.R. Akhondzadeh S. N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: A randomized, double-blind, placebo-controlled clinical trial of efficacy and safety. Clin. Neuropharmacol. 2015 38 1 11 17 10.1097/WNF.0000000000000063 25580916
    [Google Scholar]
  118. Wink L.K. Adams R. Wang Z. Klaunig J.E. Plawecki M.H. Posey D.J. McDougle C.J. Erickson C.A. A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Mol. Autism 2016 7 1 26 10.1186/s13229‑016‑0088‑6 27103982
    [Google Scholar]
  119. Lee T.M. Lee K.M. Lee C.Y. Lee H.C. Tam K.W. Loh E.W. Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials. Aust. N. Z. J. Psychiatry 2021 55 2 196 206 10.1177/0004867420952540 32900213
    [Google Scholar]
  120. Barkley R.A. History of ADHD. Attention-Deficit Hyperactivity Disorder: A handbook for diagnosis and treatment. 4th Ed New York, NY, US The Guilford Press 2015 3 50
    [Google Scholar]
  121. Garcia R.J. Francis L. Dawood M. Lai Z.W. Faraone S.V. Perl A. Attention deficit and hyperactivity disorder scores are elevated and respond to N-acetylcysteine treatment in patients with systemic lupus erythematosus. Arthritis Rheum. 2013 65 5 1313 1318 10.1002/art.37893 23400548
    [Google Scholar]
  122. Grant J.E. Odlaug B.L. Chamberlain S.R. Potenza M.N. Schreiber L.R.N. Donahue C.B. Kim S.W. A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers. J. Clin. Psychiatry 2014 75 1 39 45 10.4088/JCP.13m08411 24345329
    [Google Scholar]
  123. Cullen K.R. Klimes-Dougan B. Westlund Schreiner M. Carstedt P. Marka N. Nelson K. Miller M.J. Reigstad K. Westervelt A. Gunlicks-Stoessel M. Eberly L.E. N -Acetylcysteine for nonsuicidal self-injurious behavior in adolescents: An open-label pilot study. J. Child Adolesc. Psychopharmacol. 2018 28 2 136 144 10.1089/cap.2017.0032 29053023
    [Google Scholar]
  124. Sahasrabudhe S.A. Silamongkol T. Park Y.W. Colette A. Eberly L.E. Klimes-Dougan B. Coles L.D. Cloyd J.C. Öz G. Mueller B.A. Kartha R.V. Cullen K.R. Identifying biological signatures of N-Acetylcysteine for non-suicidal self-injury in adolescents and young adults †. J. Psychiatr. Brain Sci. 2021 6 2 210007 10.20900/jpbs.20210007 34036177
    [Google Scholar]
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