title: N-acetylcysteine for treating cocaine addiction - A systematic review.
abstract: The aim of this paper is to extensively review the current literature available on N-acetylcysteine (NAC) treatment for cocaine dependence (clinical and experimental studies). We screened all articles published before February 2016 reporting on the use of NAC as a pharmacological intervention for cocaine dependence or discussed its potential as a therapeutic approach for cocaine dependence. We described our results qualitatively. 21 studies matched our search criteria: 6 clinical trials and 15 animal studies. Four clinical studies showed NAC's capacity to reduce craving, desire to use cocaine, cocaine-cue viewing-time and cocaine-related spending. Studies in animal models also support this reinstatement prevention application of NAC. NAC reverses the disruption of glutamate homeostasis caused by long-term cocaine use restoring function of the cystine-glutamate exchanger in glial cells and reversing the downregulated GLT-1 receptor. Current data suggest promising potential for NAC as an anti-relapse agent, as a double-blind placebo trial was mainly negative, except in the subgroup of patients who were already abstinent. An optimal dose for relapse prevention may be one that restores extrasynaptic glutamate to physiological levels and predominantly activates mGluR2 and 3, but not mGluR5 receptors, which are linked to relapse. NAC may be better suited for avoiding relapse in already abstinent subjects.
authors.affiliation: Addiction Unit (PROAD), Department of Psychiatry, Federal University of São Paulo, Avenida Professor Ascendino Reis, 763 - Vila Clementino, São Paulo, SP CEP 04027-040. Brazil. Electronic address: marco_eche@hotmail.com.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Nocito Echevarria
authors.affiliation: Addiction Unit (PROAD), Department of Psychiatry, Federal University of São Paulo, Avenida Professor Ascendino Reis, 763 - Vila Clementino, São Paulo, SP CEP 04027-040. Brazil.
authors.forename: Tassio
authors.initials: T
authors.lastname: Andrade Reis
authors.affiliation: Addiction Unit (PROAD), Department of Psychiatry, Federal University of São Paulo, Avenida Professor Ascendino Reis, 763 - Vila Clementino, São Paulo, SP CEP 04027-040. Brazil.
authors.forename: Giulianno
authors.initials: G
authors.lastname: Ruffo Capatti
authors.affiliation: Addiction Unit (PROAD), Department of Psychiatry, Federal University of São Paulo, Avenida Professor Ascendino Reis, 763 - Vila Clementino, São Paulo, SP CEP 04027-040. Brazil.
authors.forename: Victor
authors.initials: V
authors.lastname: Siciliano Soares
authors.affiliation: Addiction Unit (PROAD), Department of Psychiatry, Federal University of São Paulo, Avenida Professor Ascendino Reis, 763 - Vila Clementino, São Paulo, SP CEP 04027-040. Brazil.
authors.forename: Dartiu Xavier
authors.initials: DX
authors.lastname: da Silveira
authors.affiliation: Addiction Unit (PROAD), Department of Psychiatry, Federal University of São Paulo, Avenida Professor Ascendino Reis, 763 - Vila Clementino, São Paulo, SP CEP 04027-040. Brazil.
authors.forename: Thiago Marques
authors.initials: TM
authors.lastname: Fidalgo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects; D006801:Humans; D008297:Male; D064529:Receptor, Metabotropic Glutamate 5 / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects; D012008:Recurrence; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D018698:Glutamic Acid; D000111:Acetylcysteine