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Published in: Current Addiction Reports 4/2022

01-12-2022 | Addiction | Hot Topic

The Potential of N-acetyl Cysteine in Behavioral Addictions and Related Compulsive and Impulsive Behaviors and Disorders: a Scoping Review

Authors: Norman R. Greenberg, Farzaneh Farhadi, Benjamin Kazer, Marc N. Potenza, Gustavo A. Angarita

Published in: Current Addiction Reports | Issue 4/2022

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Abstract

Purpose of Review

Behavioral addictions (also termed disorders due to addictive behaviors) contain impulsive and compulsive features and have been shown to involve glutamate dysregulation. N-acetylcysteine (NAC), a well-tolerated cysteine pro-drug and antioxidant, may reduce addictive behaviors by restoring glutamate homeostasis. The current review details and discusses the use of NAC in behavioral addictions and related impulsive and compulsive behaviors, including gambling disorder, problematic use of the internet, problematic video gaming, compulsive sexual behavior, problematic shopping/buying, problematic stealing, repetitive self-injurious behavior, and binge eating disorder.

Recent Findings

Preliminary results have indicated the usefulness of NAC in gambling disorder, self-injurious behaviors, and compulsive sexual behaviors. Preclinical studies indicate that NAC is effective in improving binge eating behavior, but clinical trials are limited to a small open-label trial and case report. Studies are lacking on the efficacy of NAC in problematic use of the internet, problematic video gaming, problematic stealing, and problematic shopping/buying.

Summary

NAC demonstrates potential for use in behavioral addictions and compulsive behaviors, particularly in gambling disorder and self-injury. However, more studies are needed to assess the effectiveness of NAC in other behavioral addictions and the mechanisms by which NAC improves these conditions.
Appendix
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Literature
1.
go back to reference • Grant JE, Potenza MN, Weinstein A, Gorelick DA. Introduction to behavioral addictions. Am J Drug Alcohol Abuse. 2010;36(5):233–41. This article reviews common clinical features, epidemiologic characteristics, neurobiological processes, diagnostic considerations, and treatment of behavioral addictions.PubMedPubMedCentralCrossRef • Grant JE, Potenza MN, Weinstein A, Gorelick DA. Introduction to behavioral addictions. Am J Drug Alcohol Abuse. 2010;36(5):233–41. This article reviews common clinical features, epidemiologic characteristics, neurobiological processes, diagnostic considerations, and treatment of behavioral addictions.PubMedPubMedCentralCrossRef
2.
go back to reference Brand M, Rumpf HJ, Demetrovics Z, MÜller A, Stark R, King DL, et al. Which conditions should be considered as disorders in the International Classification of Diseases (ICD-11) designation of “other specified disorders due to addictive behaviors”? J Behav Addict. 2020;11(2):150–9.PubMedPubMedCentral Brand M, Rumpf HJ, Demetrovics Z, MÜller A, Stark R, King DL, et al. Which conditions should be considered as disorders in the International Classification of Diseases (ICD-11) designation of “other specified disorders due to addictive behaviors”? J Behav Addict. 2020;11(2):150–9.PubMedPubMedCentral
3.
go back to reference American Psychiatric A. Diagnostic and statistical manual of mental disorders. American Psychiatric Association; 2013.CrossRef American Psychiatric A. Diagnostic and statistical manual of mental disorders. American Psychiatric Association; 2013.CrossRef
4.
go back to reference Potenza MN. Neurobiological considerations in understanding behavioral treatments for pathological gambling. Psychol Addict Behav. 2013;27(2):380–92.PubMedPubMedCentralCrossRef Potenza MN. Neurobiological considerations in understanding behavioral treatments for pathological gambling. Psychol Addict Behav. 2013;27(2):380–92.PubMedPubMedCentralCrossRef
5.
go back to reference Brand M, Wegmann E, Stark R, Müller A, Wölfling K, Robbins TW, et al. The interaction of person-affect-cognition-execution (I-PACE) model for addictive behaviors: update, generalization to addictive behaviors beyond internet-use disorders, and specification of the process character of addictive behaviors. Neurosci Biobehav Rev. 2019;104:1–10.PubMedCrossRef Brand M, Wegmann E, Stark R, Müller A, Wölfling K, Robbins TW, et al. The interaction of person-affect-cognition-execution (I-PACE) model for addictive behaviors: update, generalization to addictive behaviors beyond internet-use disorders, and specification of the process character of addictive behaviors. Neurosci Biobehav Rev. 2019;104:1–10.PubMedCrossRef
7.
go back to reference Nixon MK, Cloutier PF, Aggarwal S. Affect regulation and addictive aspects of repetitive self-injury in hospitalized adolescents. J Am Acad Child Adolesc Psychiatry. 2002;41(11):1333–41.PubMedCrossRef Nixon MK, Cloutier PF, Aggarwal S. Affect regulation and addictive aspects of repetitive self-injury in hospitalized adolescents. J Am Acad Child Adolesc Psychiatry. 2002;41(11):1333–41.PubMedCrossRef
8.
go back to reference Himelein-Wachowiak M, Giorgi S, Kwarteng A, Schriefer D, Smitterberg C, Yadeta K, et al. Getting “clean” from nonsuicidal self-injury: experiences of addiction on the subreddit r/selfharm. J Behav Addict. 2022;11(1):128–39.PubMedPubMedCentralCrossRef Himelein-Wachowiak M, Giorgi S, Kwarteng A, Schriefer D, Smitterberg C, Yadeta K, et al. Getting “clean” from nonsuicidal self-injury: experiences of addiction on the subreddit r/selfharm. J Behav Addict. 2022;11(1):128–39.PubMedPubMedCentralCrossRef
9.
go back to reference Meule A, Gearhardt AN. Five years of the Yale food addiction scale: taking stock and moving forward. Curr Addict Rep. 2014;1(3):193–205.CrossRef Meule A, Gearhardt AN. Five years of the Yale food addiction scale: taking stock and moving forward. Curr Addict Rep. 2014;1(3):193–205.CrossRef
10.
go back to reference Liu C, Rotaru K, Lee RSC, Tiego J, Suo C, Yücel M, et al. Distress-driven impulsivity interacts with cognitive inflexibility to determine addiction-like eating. J Behav Addict. 2021;10(3):534–9.PubMedPubMedCentralCrossRef Liu C, Rotaru K, Lee RSC, Tiego J, Suo C, Yücel M, et al. Distress-driven impulsivity interacts with cognitive inflexibility to determine addiction-like eating. J Behav Addict. 2021;10(3):534–9.PubMedPubMedCentralCrossRef
11.
go back to reference Schreiber LR, Odlaug BL, Grant JE. The overlap between binge eating disorder and substance use disorders: diagnosis and neurobiology. J Behav Addict. 2013;2(4):191–8.PubMedPubMedCentralCrossRef Schreiber LR, Odlaug BL, Grant JE. The overlap between binge eating disorder and substance use disorders: diagnosis and neurobiology. J Behav Addict. 2013;2(4):191–8.PubMedPubMedCentralCrossRef
12.
go back to reference Rømer Thomsen K, Callesen MB, Hesse M, Kvamme TL, Pedersen MM, Pedersen MU, et al. Impulsivity traits and addiction-related behaviors in youth. J Behav Addict. 2018;7(2):317–30.PubMedPubMedCentralCrossRef Rømer Thomsen K, Callesen MB, Hesse M, Kvamme TL, Pedersen MM, Pedersen MU, et al. Impulsivity traits and addiction-related behaviors in youth. J Behav Addict. 2018;7(2):317–30.PubMedPubMedCentralCrossRef
13.
go back to reference Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT, et al. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology. 2006;184(2):254–6.PubMedCrossRef Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT, et al. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology. 2006;184(2):254–6.PubMedCrossRef
14.
go back to reference Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005;30(9):1735–40.PubMedCrossRef Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005;30(9):1735–40.PubMedCrossRef
15.
go back to reference Lee DK, Lipner SR. The potential of N-acetylcysteine for treatment of trichotillomania, excoriation disorder, onychophagia, and onychotillomania: an updated literature review. Int J Environ Res Public Health. 2022;19(11):6370.PubMedPubMedCentralCrossRef Lee DK, Lipner SR. The potential of N-acetylcysteine for treatment of trichotillomania, excoriation disorder, onychophagia, and onychotillomania: an updated literature review. Int J Environ Res Public Health. 2022;19(11):6370.PubMedPubMedCentralCrossRef
16.
go back to reference Smaga I, Frankowska M, Filip M. N-acetylcysteine in substance use disorder: a lesson from preclinical and clinical research. Pharmacol Rep. 2021;73(5):1205–19.PubMedPubMedCentralCrossRef Smaga I, Frankowska M, Filip M. N-acetylcysteine in substance use disorder: a lesson from preclinical and clinical research. Pharmacol Rep. 2021;73(5):1205–19.PubMedPubMedCentralCrossRef
17.
go back to reference Duailibi MS, Cordeiro Q, Brietzke E, Ribeiro M, LaRowe S, Berk M, et al. N-acetylcysteine in the treatment of craving in substance use disorders: systematic review and meta-analysis. Am J Addict. 2017;26(7):660–6.PubMedCrossRef Duailibi MS, Cordeiro Q, Brietzke E, Ribeiro M, LaRowe S, Berk M, et al. N-acetylcysteine in the treatment of craving in substance use disorders: systematic review and meta-analysis. Am J Addict. 2017;26(7):660–6.PubMedCrossRef
18.
go back to reference McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM. Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs. 2014;28(2):95–106.PubMedPubMedCentralCrossRef McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM. Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs. 2014;28(2):95–106.PubMedPubMedCentralCrossRef
19.
go back to reference • Kalivas PW. The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci. 2009;10(8):561–72. This article reviews and details the mechanisms by which glutamate dysregulation affects addiction and relapse behavior.PubMedCrossRef • Kalivas PW. The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci. 2009;10(8):561–72. This article reviews and details the mechanisms by which glutamate dysregulation affects addiction and relapse behavior.PubMedCrossRef
20.
go back to reference Deepmala, Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neurosci Biobehav Rev. 2015;55:294–321. Deepmala, Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neurosci Biobehav Rev. 2015;55:294–321.
21.
go back to reference Grant JE, Odlaug BL, Won KS. N-Acetylcysteine, a Glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009;66(7):756–63.PubMedCrossRef Grant JE, Odlaug BL, Won KS. N-Acetylcysteine, a Glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009;66(7):756–63.PubMedCrossRef
22.
go back to reference • Nocito Echevarria MA, Andrade Reis T, Ruffo Capatti G, Siciliano Soares V, da Silveira DX, Fidalgo TM. N-acetylcysteine for treating cocaine addiction - a systematic review. Psychiatry Res. 2017;251:197–203. This paper reviews preclinical and clinical trials (from before 2016) assessing NAC’s effects in cocaine use disorder. The reviewed papers suggest that NAC is effective in reducing reinstatement of cocaine-seeking in prelinical trials and preventing relapse in clinical trials.PubMedCrossRef • Nocito Echevarria MA, Andrade Reis T, Ruffo Capatti G, Siciliano Soares V, da Silveira DX, Fidalgo TM. N-acetylcysteine for treating cocaine addiction - a systematic review. Psychiatry Res. 2017;251:197–203. This paper reviews preclinical and clinical trials (from before 2016) assessing NAC’s effects in cocaine use disorder. The reviewed papers suggest that NAC is effective in reducing reinstatement of cocaine-seeking in prelinical trials and preventing relapse in clinical trials.PubMedCrossRef
23.
go back to reference Asevedo E, Mendes AC, Berk M, Brietzke E. Systematic review of N-acetylcysteine in the treatment of addictions. Braz J Psychiatry. 2014;36(2):168–75.PubMedCrossRef Asevedo E, Mendes AC, Berk M, Brietzke E. Systematic review of N-acetylcysteine in the treatment of addictions. Braz J Psychiatry. 2014;36(2):168–75.PubMedCrossRef
24.
go back to reference Smaga I, Frankowska M, Filip M. N-acetylcysteine in substance use disorder: a lesson from preclinical and clinical research. Pharmacol Rep. 2021;73(5):1205–19.PubMedPubMedCentralCrossRef Smaga I, Frankowska M, Filip M. N-acetylcysteine in substance use disorder: a lesson from preclinical and clinical research. Pharmacol Rep. 2021;73(5):1205–19.PubMedPubMedCentralCrossRef
25.
go back to reference di Michele F, Siracusano A, Talamo A, Niolu C. N-acetyl cysteine and vitamin D supplementation in treatment resistant obsessive-compulsive disorder patients: a general review. Curr Pharm Des. 2018;24(17):1832–8.PubMedCrossRef di Michele F, Siracusano A, Talamo A, Niolu C. N-acetyl cysteine and vitamin D supplementation in treatment resistant obsessive-compulsive disorder patients: a general review. Curr Pharm Des. 2018;24(17):1832–8.PubMedCrossRef
26.
go back to reference Marler S, Sanders KB, Veenstra-VanderWeele J. N-acetylcysteine as treatment for self-injurious behavior in a child with autism. J Child Adolesc Psychopharmacol. 2014;24(4):231–4.PubMedCrossRef Marler S, Sanders KB, Veenstra-VanderWeele J. N-acetylcysteine as treatment for self-injurious behavior in a child with autism. J Child Adolesc Psychopharmacol. 2014;24(4):231–4.PubMedCrossRef
27.
go back to reference Sabus A, Feinstein J, Romani P, Goldson E, Blackmer A. Management of self-injurious behaviors in children with neurodevelopmental disorders: a pharmacotherapy overview. Pharmacotherapy. 2019;39(6):645–64.PubMedPubMedCentralCrossRef Sabus A, Feinstein J, Romani P, Goldson E, Blackmer A. Management of self-injurious behaviors in children with neurodevelopmental disorders: a pharmacotherapy overview. Pharmacotherapy. 2019;39(6):645–64.PubMedPubMedCentralCrossRef
28.
go back to reference Miller JL, Angulo M. An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome. Am J Med Genet A. 2014;164a(2):421–4.PubMedCrossRef Miller JL, Angulo M. An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome. Am J Med Genet A. 2014;164a(2):421–4.PubMedCrossRef
29.
go back to reference Kiliç F, Keleş S. Repetitive behaviors treated with N-acetylcysteine: case series. Clin Neuropharmacol. 2019;42(4):139–41.PubMedCrossRef Kiliç F, Keleş S. Repetitive behaviors treated with N-acetylcysteine: case series. Clin Neuropharmacol. 2019;42(4):139–41.PubMedCrossRef
30.
go back to reference Pesko MJ, Burbige EM, Sannar EM, Beresford C, Rogers C, Ariefdjohan M, et al. The use of N-acetylcysteine supplementation to decrease irritability in four youths with autism spectrum disorders. J Pediatr Pharmacol Ther. 2020;25(2):149–54.PubMedPubMedCentral Pesko MJ, Burbige EM, Sannar EM, Beresford C, Rogers C, Ariefdjohan M, et al. The use of N-acetylcysteine supplementation to decrease irritability in four youths with autism spectrum disorders. J Pediatr Pharmacol Ther. 2020;25(2):149–54.PubMedPubMedCentral
31.
go back to reference Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012;71(11):956–61.PubMedPubMedCentralCrossRef Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012;71(11):956–61.PubMedPubMedCentralCrossRef
32.
go back to reference McFarland K, Lapish CC, Kalivas PW. Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci. 2003;23(8):3531–7.PubMedPubMedCentralCrossRef McFarland K, Lapish CC, Kalivas PW. Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci. 2003;23(8):3531–7.PubMedPubMedCentralCrossRef
33.
go back to reference Baker DA, McFarland K, Lake RW, Shen H, Tang XC, Toda S, et al. Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci. 2003;6(7):743–9.PubMedCrossRef Baker DA, McFarland K, Lake RW, Shen H, Tang XC, Toda S, et al. Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci. 2003;6(7):743–9.PubMedCrossRef
34.
go back to reference Knackstedt LA, LaRowe S, Mardikian P, Malcolm R, Upadhyaya H, Hedden S, et al. The role of cystine-glutamate exchange in nicotine dependence in rats and humans. Biol Psychiatry. 2009;65(10):841–5.PubMedCrossRef Knackstedt LA, LaRowe S, Mardikian P, Malcolm R, Upadhyaya H, Hedden S, et al. The role of cystine-glutamate exchange in nicotine dependence in rats and humans. Biol Psychiatry. 2009;65(10):841–5.PubMedCrossRef
35.
go back to reference Berk M. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci (Regular ed). 2013;34(3):167–77.CrossRef Berk M. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci (Regular ed). 2013;34(3):167–77.CrossRef
36.
go back to reference Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, et al. N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review. Clin Psychopharmacol Neurosci. 2015;13(1):12–24.PubMedPubMedCentralCrossRef Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, et al. N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review. Clin Psychopharmacol Neurosci. 2015;13(1):12–24.PubMedPubMedCentralCrossRef
37.
38.
go back to reference Toce-Gerstein M, Gerstein DR, Volberg RA. The NODS–CLiP: a rapid screen for adult pathological and problem gambling. J Gambl Stud. 2009;25(4):541–55.PubMedPubMedCentralCrossRef Toce-Gerstein M, Gerstein DR, Volberg RA. The NODS–CLiP: a rapid screen for adult pathological and problem gambling. J Gambl Stud. 2009;25(4):541–55.PubMedPubMedCentralCrossRef
39.
go back to reference Pasternak Iv AV. Prevalence of gambling disorders in a primary care setting. Arch Fam Med. 1999;8(6):515–20.CrossRef Pasternak Iv AV. Prevalence of gambling disorders in a primary care setting. Arch Fam Med. 1999;8(6):515–20.CrossRef
40.
go back to reference Hodgins DC, Stea JN, Grant JE. Gambling disorders. The Lancet. 2011;378(9806):1874–84.CrossRef Hodgins DC, Stea JN, Grant JE. Gambling disorders. The Lancet. 2011;378(9806):1874–84.CrossRef
41.
go back to reference Nordin C, Gupta RC, Sjodin I. Cerebrospinal fluid amino acids in pathological gamblers and healthy controls. Neuropsychobiology. 2007;56(2–3):152–8.PubMedCrossRef Nordin C, Gupta RC, Sjodin I. Cerebrospinal fluid amino acids in pathological gamblers and healthy controls. Neuropsychobiology. 2007;56(2–3):152–8.PubMedCrossRef
42.
go back to reference Pettorruso M, De Risio L, Martinotti G, Di Nicola M, Ruggeri F, Conte G, et al. Targeting the glutamatergic system to treat pathological gambling: current evidence and future perspectives. Biomed Res Int. 2014;2014:1–11.CrossRef Pettorruso M, De Risio L, Martinotti G, Di Nicola M, Ruggeri F, Conte G, et al. Targeting the glutamatergic system to treat pathological gambling: current evidence and future perspectives. Biomed Res Int. 2014;2014:1–11.CrossRef
43.
go back to reference Black DW, McNeilly DP, Burke WJ, Shaw MC, Allen J. An open-label trial of acamprosate in the treatment of pathological gambling. Ann Clin Psychiatry. 2011;23(4):250–6.PubMed Black DW, McNeilly DP, Burke WJ, Shaw MC, Allen J. An open-label trial of acamprosate in the treatment of pathological gambling. Ann Clin Psychiatry. 2011;23(4):250–6.PubMed
44.
go back to reference Pettorruso M, Martinotti G, Di Nicola M, Onofrj M, Di Giannantonio M, Conte G, et al. Amantadine in the treatment of pathological gambling: a case report. Front Psychiatry. 2012;3:102.PubMedPubMedCentralCrossRef Pettorruso M, Martinotti G, Di Nicola M, Onofrj M, Di Giannantonio M, Conte G, et al. Amantadine in the treatment of pathological gambling: a case report. Front Psychiatry. 2012;3:102.PubMedPubMedCentralCrossRef
45.
go back to reference Thomas A, Bonanni L, Gambi F, Di Iorio A, Onofrj M. Pathological gambling in Parkinson disease is reduced by amantadine. Ann Neurol. 2010;68(3):400–4.PubMedCrossRef Thomas A, Bonanni L, Gambi F, Di Iorio A, Onofrj M. Pathological gambling in Parkinson disease is reduced by amantadine. Ann Neurol. 2010;68(3):400–4.PubMedCrossRef
46.
go back to reference Grant JE, Chamberlain SR, Odlaug BL, Potenza MN, Kim SW. Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study. Psychopharmacology. 2010;212(4):603–12.PubMedPubMedCentralCrossRef Grant JE, Chamberlain SR, Odlaug BL, Potenza MN, Kim SW. Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study. Psychopharmacology. 2010;212(4):603–12.PubMedPubMedCentralCrossRef
47.
go back to reference Dannon PN, Lowengrub K, Gonopolski Y, Musin E, Kotler M. Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clin Neuropharmacol. 2005;28(1):6–10.PubMedCrossRef Dannon PN, Lowengrub K, Gonopolski Y, Musin E, Kotler M. Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clin Neuropharmacol. 2005;28(1):6–10.PubMedCrossRef
48.
go back to reference Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry (1969). 2007;62(6):652–7.CrossRef Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry (1969). 2007;62(6):652–7.CrossRef
49.
go back to reference Grant JE, Odlaug BL, Chamberlain SR, Potenza MN, Schreiber LRN, Donahue CB, et al. A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers. J Clin Psychiatry. 2014;75:39–45.PubMedCrossRef Grant JE, Odlaug BL, Chamberlain SR, Potenza MN, Schreiber LRN, Donahue CB, et al. A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers. J Clin Psychiatry. 2014;75:39–45.PubMedCrossRef
51.
go back to reference Schmaal L, Veltman DJ, Nederveen A, van den Brink W, Goudriaan AE. N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients: a randomized crossover magnetic resonance spectroscopy study. Neuropsychopharmacology. 2012;37(9):2143–52.PubMedPubMedCentralCrossRef Schmaal L, Veltman DJ, Nederveen A, van den Brink W, Goudriaan AE. N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients: a randomized crossover magnetic resonance spectroscopy study. Neuropsychopharmacology. 2012;37(9):2143–52.PubMedPubMedCentralCrossRef
52.
go back to reference •• Woodcock EA, Lundahl LH, Khatib D, Stanley JA, Greenwald MK. N -acetylcysteine reduces cocaine-seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine-dependent individuals. Addict Biol. 2021;26(2): e12900. This clinical trial of 12 participants with cocaine use disorder assessed the use of 3600 mg/day of NAC on cocaine-primed increases in cocaine-seeking and on brain glutamate levels measured with proton magnetic resonance spectroscopy. NAC significantly reduced cocaine-seeking in the test and reduced rACC glutamate and glutamine levels.PubMedCrossRef •• Woodcock EA, Lundahl LH, Khatib D, Stanley JA, Greenwald MK. N -acetylcysteine reduces cocaine-seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine-dependent individuals. Addict Biol. 2021;26(2): e12900. This clinical trial of 12 participants with cocaine use disorder assessed the use of 3600 mg/day of NAC on cocaine-primed increases in cocaine-seeking and on brain glutamate levels measured with proton magnetic resonance spectroscopy. NAC significantly reduced cocaine-seeking in the test and reduced rACC glutamate and glutamine levels.PubMedCrossRef
53.
go back to reference Yip SW, Morie KP, Xu J, Constable RT, Malison RT, Carroll KM, et al. Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2(2):188–95.PubMedPubMedCentral Yip SW, Morie KP, Xu J, Constable RT, Malison RT, Carroll KM, et al. Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2(2):188–95.PubMedPubMedCentral
54.
go back to reference Yip SW, Worhunsky PD, Xu J, Morie KP, Constable RT, Malison RT, et al. Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions. Addict Biol. 2018;23(1):394–402.PubMedCrossRef Yip SW, Worhunsky PD, Xu J, Morie KP, Constable RT, Malison RT, et al. Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions. Addict Biol. 2018;23(1):394–402.PubMedCrossRef
55.
go back to reference Worhunsky PD, Malison RT, Rogers RD, Potenza MN. Altered neural correlates of reward and loss processing during simulated slot-machine fMRI in pathological gambling and cocaine dependence. Drug Alcohol Depend. 2014;145:77–86.PubMedPubMedCentralCrossRef Worhunsky PD, Malison RT, Rogers RD, Potenza MN. Altered neural correlates of reward and loss processing during simulated slot-machine fMRI in pathological gambling and cocaine dependence. Drug Alcohol Depend. 2014;145:77–86.PubMedPubMedCentralCrossRef
56.
go back to reference Worhunsky PD, Potenza MN, Rogers RD. Alterations in functional brain networks associated with loss-chasing in gambling disorder and cocaine-use disorder. Drug Alcohol Depend. 2017;178:363–71.PubMedPubMedCentralCrossRef Worhunsky PD, Potenza MN, Rogers RD. Alterations in functional brain networks associated with loss-chasing in gambling disorder and cocaine-use disorder. Drug Alcohol Depend. 2017;178:363–71.PubMedPubMedCentralCrossRef
57.
go back to reference Greenberg NR, Zhai ZW, Hoff RA, Krishnan-Sarin S, Potenza MN. Problematic shopping and self-injurious behaviors in adolescents. J Behav Addict. 2020;9(4):1068–78.PubMedPubMedCentralCrossRef Greenberg NR, Zhai ZW, Hoff RA, Krishnan-Sarin S, Potenza MN. Problematic shopping and self-injurious behaviors in adolescents. J Behav Addict. 2020;9(4):1068–78.PubMedPubMedCentralCrossRef
58.
go back to reference Farhat LC, Roberto AJ, Wampler J, Steinberg MA, Krishnan-Sarin S, Hoff RA, et al. Self-injurious behavior and gambling-related attitudes, perceptions and behaviors in adolescents. J Psychiatr Res. 2020;124:77–84.PubMedCrossRef Farhat LC, Roberto AJ, Wampler J, Steinberg MA, Krishnan-Sarin S, Hoff RA, et al. Self-injurious behavior and gambling-related attitudes, perceptions and behaviors in adolescents. J Psychiatr Res. 2020;124:77–84.PubMedCrossRef
59.
go back to reference Pittenger C, Krystal JH, Coric V. Initial evidence of the beneficial effects of glutamate-modulating agents in the treatment of self-injurious behavior associated with borderline personality disorder. J Clin Psychiatry. 2005;66(11):1492–3.PubMedCrossRef Pittenger C, Krystal JH, Coric V. Initial evidence of the beneficial effects of glutamate-modulating agents in the treatment of self-injurious behavior associated with borderline personality disorder. J Clin Psychiatry. 2005;66(11):1492–3.PubMedCrossRef
60.
go back to reference •• Cullen KR, Klimes-Dougan B, Westlund Schreiner M, Carstedt P, Marka N, Nelson K, et al. N-acetylcysteine for nonsuicidal self-injurious behavior in adolescents: an open-label pilot study. J Child Adolesc Psychopharmacol. 2018;28(2):136–44. This is an open-label clinical trial of 35 female adolescents in which NAC significantly decreased SIB frequency and depression scores.PubMedPubMedCentralCrossRef •• Cullen KR, Klimes-Dougan B, Westlund Schreiner M, Carstedt P, Marka N, Nelson K, et al. N-acetylcysteine for nonsuicidal self-injurious behavior in adolescents: an open-label pilot study. J Child Adolesc Psychopharmacol. 2018;28(2):136–44. This is an open-label clinical trial of 35 female adolescents in which NAC significantly decreased SIB frequency and depression scores.PubMedPubMedCentralCrossRef
61.
go back to reference •• Cullen KR, Schreiner MW, Klimes-Dougan B, Eberly LE, LaRiviere LL, Lim KO, et al. Neural correlates of clinical improvement in response to N-acetylcysteine in adolescents with non-suicidal self-injury. Prog Neuropsychopharmacol Biol Psychiatry. 2020;99: 109778. This study used fMRI to measure resting state connectivity in 35 female adolescents using NAC to reduce SIB. They found that decreases in SIB frequency and depression scores correlated with increased amygdala-frontal connectivity and decreased amygdala-SMA connectivity.PubMedCrossRef •• Cullen KR, Schreiner MW, Klimes-Dougan B, Eberly LE, LaRiviere LL, Lim KO, et al. Neural correlates of clinical improvement in response to N-acetylcysteine in adolescents with non-suicidal self-injury. Prog Neuropsychopharmacol Biol Psychiatry. 2020;99: 109778. This study used fMRI to measure resting state connectivity in 35 female adolescents using NAC to reduce SIB. They found that decreases in SIB frequency and depression scores correlated with increased amygdala-frontal connectivity and decreased amygdala-SMA connectivity.PubMedCrossRef
62.
go back to reference Sahasrabudhe SA, Silamongkol T, Park YW, Colette A, Eberly LE, Klimes-Dougan B, et al. Identifying biological signatures of N-acetylcysteine for non-suicidal self-injury in adolescents and young adults. J Psychiatr Brain Sci. 2021;6:210007. Sahasrabudhe SA, Silamongkol T, Park YW, Colette A, Eberly LE, Klimes-Dougan B, et al. Identifying biological signatures of N-acetylcysteine for non-suicidal self-injury in adolescents and young adults. J Psychiatr Brain Sci. 2021;6:210007.
63.
go back to reference •• Hurley MM, Resch JM, Maunze B, Frenkel MM, Baker DA, Choi S. N-acetylcysteine decreases binge eating in a rodent model. Int J Obes (Lond). 2016;40(7):1183–6. This preclinical study of binge eating disorder showed that NAC significantly reduced high-carbohydrate/high-fat binge eating episodes in rats.PubMedCrossRef •• Hurley MM, Resch JM, Maunze B, Frenkel MM, Baker DA, Choi S. N-acetylcysteine decreases binge eating in a rodent model. Int J Obes (Lond). 2016;40(7):1183–6. This preclinical study of binge eating disorder showed that NAC significantly reduced high-carbohydrate/high-fat binge eating episodes in rats.PubMedCrossRef
64.
go back to reference Sketriene D, Battista D, Perry CJ, Sumithran P, Lawrence AJ, Brown RM. N-acetylcysteine reduces addiction-like behaviour towards high-fat high-sugar food in diet-induced obese rats. Eur J Neurosci. 2021;54(3):4877–87.PubMedCrossRef Sketriene D, Battista D, Perry CJ, Sumithran P, Lawrence AJ, Brown RM. N-acetylcysteine reduces addiction-like behaviour towards high-fat high-sugar food in diet-induced obese rats. Eur J Neurosci. 2021;54(3):4877–87.PubMedCrossRef
65.
go back to reference Guerdjikova AI, Blom TJ, Mori N, McElroy SL. N-acetylcysteine in bulimia nervosa–open-label trial. Eat Behav. 2013;14(1):87–9.PubMedCrossRef Guerdjikova AI, Blom TJ, Mori N, McElroy SL. N-acetylcysteine in bulimia nervosa–open-label trial. Eat Behav. 2013;14(1):87–9.PubMedCrossRef
66.
go back to reference Gray KM, Watson NL, Carpenter MJ, Larowe SD. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am J Addict. 2010;19(2):187–9.PubMedPubMedCentralCrossRef Gray KM, Watson NL, Carpenter MJ, Larowe SD. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am J Addict. 2010;19(2):187–9.PubMedPubMedCentralCrossRef
67.
go back to reference Zhao X, Wang S, Hong X, Lu S, Tang S, Shen Y, et al. A case of trichotillomania with binge eating disorder: combined with N-acetylcysteine synergistic therapy. Ann Gen Psychiatry. 2021;20(1):46.PubMedPubMedCentralCrossRef Zhao X, Wang S, Hong X, Lu S, Tang S, Shen Y, et al. A case of trichotillomania with binge eating disorder: combined with N-acetylcysteine synergistic therapy. Ann Gen Psychiatry. 2021;20(1):46.PubMedPubMedCentralCrossRef
68.
go back to reference Grant JE, Chamberlain SR, Redden SA, Leppink EW, Odlaug BL, Kim SW. N-Acetylcysteine in the treatment of excoriation disorder: a randomized clinical trial. JAMA Psychiat. 2016;73(5):490–6.CrossRef Grant JE, Chamberlain SR, Redden SA, Leppink EW, Odlaug BL, Kim SW. N-Acetylcysteine in the treatment of excoriation disorder: a randomized clinical trial. JAMA Psychiat. 2016;73(5):490–6.CrossRef
69.
go back to reference • Blum AW, Grant JE. N-acetylcysteine in the treatment of compulsive sexual behavior disorder: A case series. J Psychiatr Res. 2022;154:203–6. This is a recently published case series of 8 patients treated with NAC for compulsive sexual behavior. Five out of 8 of the participants had significant reduction in Y-BOCS score modified for compulsive sexual behavior, suggesting the therapy may be effective.PubMedCrossRef • Blum AW, Grant JE. N-acetylcysteine in the treatment of compulsive sexual behavior disorder: A case series. J Psychiatr Res. 2022;154:203–6. This is a recently published case series of 8 patients treated with NAC for compulsive sexual behavior. Five out of 8 of the participants had significant reduction in Y-BOCS score modified for compulsive sexual behavior, suggesting the therapy may be effective.PubMedCrossRef
70.
go back to reference Fong TW. Understanding and managing compulsive sexual behaviors. Psychiatry (Edgmont). 2006;3(11):51–8.PubMed Fong TW. Understanding and managing compulsive sexual behaviors. Psychiatry (Edgmont). 2006;3(11):51–8.PubMed
71.
go back to reference Moore KM, Oelberg WL, Glass MR, Johnson MD, Been LE, Meisel RL. Glutamate Afferents from the medial prefrontal cortex mediate nucleus accumbens activation by female sexual behavior. Front Behav Neurosci. 2019;13:227.PubMedPubMedCentralCrossRef Moore KM, Oelberg WL, Glass MR, Johnson MD, Been LE, Meisel RL. Glutamate Afferents from the medial prefrontal cortex mediate nucleus accumbens activation by female sexual behavior. Front Behav Neurosci. 2019;13:227.PubMedPubMedCentralCrossRef
72.
go back to reference Voon V, Mole TB, Banca P, Porter L, Morris L, Mitchell S, et al. Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours. PLoS ONE. 2014;9(7): e102419.PubMedPubMedCentralCrossRef Voon V, Mole TB, Banca P, Porter L, Morris L, Mitchell S, et al. Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours. PLoS ONE. 2014;9(7): e102419.PubMedPubMedCentralCrossRef
73.
go back to reference Grant JE, Odlaug BL, Mooney M, O’Brien R, Kim SW. Open-label pilot study of memantine in the treatment of compulsive buying. Ann Clin Psychiatry. 2012;24(2):119–26.PubMed Grant JE, Odlaug BL, Mooney M, O’Brien R, Kim SW. Open-label pilot study of memantine in the treatment of compulsive buying. Ann Clin Psychiatry. 2012;24(2):119–26.PubMed
74.
go back to reference Paik S-H, Choi MR, Kwak SM, Bang SH, Kim D-J. Decreased serum glutamate levels in male adults with Internet gaming disorder: a pilot study. Clin Psychopharmacol Neurosci. 2018;16(3):276–81.PubMedPubMedCentralCrossRef Paik S-H, Choi MR, Kwak SM, Bang SH, Kim D-J. Decreased serum glutamate levels in male adults with Internet gaming disorder: a pilot study. Clin Psychopharmacol Neurosci. 2018;16(3):276–81.PubMedPubMedCentralCrossRef
75.
go back to reference Seo HS, Jeong EK, Choi S, Kwon Y, Park HJ, Kim I. Changes of neurotransmitters in youth with Internet and smartphone addiction: a comparison with healthy controls and changes after cognitive behavioral therapy. AJNR Am J Neuroradiol. 2020;41(7):1293–301.PubMedPubMedCentralCrossRef Seo HS, Jeong EK, Choi S, Kwon Y, Park HJ, Kim I. Changes of neurotransmitters in youth with Internet and smartphone addiction: a comparison with healthy controls and changes after cognitive behavioral therapy. AJNR Am J Neuroradiol. 2020;41(7):1293–301.PubMedPubMedCentralCrossRef
76.
go back to reference Fineberg NA, Demetrovics Z, Stein DJ, Ioannidis K, Potenza MN, Grünblatt E, et al. Manifesto for a European research network into problematic usage of the Internet. Eur Neuropsychopharmacol. 2018;28(11):1232–46.PubMedPubMedCentralCrossRef Fineberg NA, Demetrovics Z, Stein DJ, Ioannidis K, Potenza MN, Grünblatt E, et al. Manifesto for a European research network into problematic usage of the Internet. Eur Neuropsychopharmacol. 2018;28(11):1232–46.PubMedPubMedCentralCrossRef
77.
go back to reference Yang S, Salmeron BJ, Ross TJ, Xi ZX, Stein EA, Yang Y. Lower glutamate levels in rostral anterior cingulate of chronic cocaine users - a (1)H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy. Psychiatry Res. 2009;174(3):171–6.PubMedPubMedCentralCrossRef Yang S, Salmeron BJ, Ross TJ, Xi ZX, Stein EA, Yang Y. Lower glutamate levels in rostral anterior cingulate of chronic cocaine users - a (1)H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy. Psychiatry Res. 2009;174(3):171–6.PubMedPubMedCentralCrossRef
78.
go back to reference Engeli EJE, Zoelch N, Hock A, Nordt C, Hulka LM, Kirschner M, et al. Impaired glutamate homeostasis in the nucleus accumbens in human cocaine addiction. Mol Psychiatry. 2020;26:5277–85.PubMedCrossRef Engeli EJE, Zoelch N, Hock A, Nordt C, Hulka LM, Kirschner M, et al. Impaired glutamate homeostasis in the nucleus accumbens in human cocaine addiction. Mol Psychiatry. 2020;26:5277–85.PubMedCrossRef
79.
go back to reference Galyuk TM, Loonen AJM. Putative role of vitamin D in the mechanism of alcoholism and other addictions – a hypothesis. Acta Neuropsychiatrica. 2021;33(1):1–8.PubMedCrossRef Galyuk TM, Loonen AJM. Putative role of vitamin D in the mechanism of alcoholism and other addictions – a hypothesis. Acta Neuropsychiatrica. 2021;33(1):1–8.PubMedCrossRef
81.
go back to reference Trinko JR, Land BB, Solecki WB, Wickham RJ, Tellez LA, Maldonado-Aviles J, et al. Vitamin D3: a role in dopamine circuit regulation, diet-induced obesity, and drug consumption. eNeuro. 2016;3(2):ENEURO.0122-15.2016. Trinko JR, Land BB, Solecki WB, Wickham RJ, Tellez LA, Maldonado-Aviles J, et al. Vitamin D3: a role in dopamine circuit regulation, diet-induced obesity, and drug consumption. eNeuro. 2016;3(2):ENEURO.0122-15.2016.
Metadata
Title
The Potential of N-acetyl Cysteine in Behavioral Addictions and Related Compulsive and Impulsive Behaviors and Disorders: a Scoping Review
Authors
Norman R. Greenberg
Farzaneh Farhadi
Benjamin Kazer
Marc N. Potenza
Gustavo A. Angarita
Publication date
01-12-2022
Publisher
Springer International Publishing
Published in
Current Addiction Reports / Issue 4/2022
Electronic ISSN: 2196-2952
DOI
https://doi.org/10.1007/s40429-022-00446-3

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