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acetylcysteine cocaine

Mieke H J Schulte, Reinout W Wiers, Wouter J Boendermaker, Anna E Goudriaan, Wim van den Brink, Denise S van Deursen, Malte Friese, Emily Brede, Andrew J Waters
INTRODUCTION: Effective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data...
August 2018: Addictive Behaviors
Sergios Charntikov, Steven T Pittenger, Cindy M Pudiak, Rick A Bevins
N-acetylcysteine and bupropion are two promising candidate medications for treatment of substance use disorder. The effects of N-acetylcysteine or bupropion on methamphetamine self-administration of female rats are not well understood. To fill this gap, this study assessed the effects of N-acetylcysteine (0, 30, 60, or 120 mg/kg) and bupropion (0, 10, 30, and 60 mg/kg) on methamphetamine self-administration of female rats across the natural estrous cycle. Following a completed dose-response curve, responding for methamphetamine self-administration was extinguished and the effects of N-acetylcysteine or bupropion on methamphetamine-triggered reinstatement was evaluated in separate experiments...
June 2018: Neuropharmacology
Ritchy Hodebourg, Jennifer E Murray, Maxime Fouyssac, Mickaël Puaud, Barry J Everitt, David Belin
The alarming increase in heroin overdoses in the USA is a reminder of the need for efficacious and novel treatments for opiate addiction. This may reflect the relatively poor understanding of the neural basis of heroin, as compared to cocaine, seeking behaviour. While cocaine reinforcement depends on the mesolimbic system, well-established cocaine seeking is dependent on dorsolateral striatum (aDLS) dopamine-dependent mechanisms which are disrupted by N-acetylcysteine, through normalisation of corticostriatal glutamate homeostasis...
March 7, 2018: European Journal of Neuroscience
Mieke H J Schulte, Reinout W Wiers, Wouter J Boendermaker, Anna E Goudriaan, Wim van den Brink, Denise S van Deursen, Malte Friese, Emily Brede, Andrew J Waters
INTRODUCTION: Effective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data...
April 2018: Addictive Behaviors
B Levi Bolin, Joseph L Alcorn, Joshua A Lile, Craig R Rush, Abner O Rayapati, Lon R Hays, William W Stoops
BACKGROUND: Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. METHODS: The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60mg)...
September 1, 2017: Drug and Alcohol Dependence
Marco Antonio Nocito Echevarria, Tassio Andrade Reis, Giulianno Ruffo Capatti, Victor Siciliano Soares, Dartiu Xavier da Silveira, Thiago Marques Fidalgo
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...
May 2017: Psychiatry Research
Joanna Jastrzębska, Malgorzata Frankowska, Malgorzata Filip, Daphne Atlas
RATIONALE: Chronic exposure to drugs of abuse changes glutamatergic transmission in human addicts and animal models. N-acetylcysteine (NAC) is a cysteine prodrug that indirectly activates cysteine-glutamate antiporters. In the extrasynaptic space, NAC restores basal glutamate levels during drug abstinence and normalizes increased glutamatergic tone in rats during reinstatement to drugs of abuse. In initial clinical trials, repeated NAC administration seems to be promising for reduced craving in cocaine addicts...
September 2016: Psychopharmacology
Manuela Graziani, Letizia Antonilli, Anna Rita Togna, Maria Caterina Grassi, Aldo Badiani, Luciano Saso
Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity...
2016: Oxidative Medicine and Cellular Longevity
Eric Ducret, Mickaël Puaud, Jérôme Lacoste, Aude Belin-Rauscent, Maxime Fouyssac, Emilie Dugast, Jennifer E Murray, Barry J Everitt, Jean-Luc Houeto, David Belin
BACKGROUND: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown. METHODS: We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation...
August 1, 2016: Biological Psychiatry
Steven D LaRowe, Peter W Kalivas
Previous work has found that N-acetylcysteine inhibits extinction responding in rats trained to self-administer heroin. The current study examined the ability of N-acetylcysteine to inhibit extinction responding in rats trained to self-administer cocaine. Rats were trained to self-administer cocaine (0.39mg/kg) for 10 to 12 days and were pretreated with either N-acetylcysteine (60mg/kg) or saline beginning on the first day of extinction training and on each extinction training day thereafter. Results indicated that chronically administered N-acetylcysteine reduced lever pressing during extinction sessions...
2010: Open Addiction Journal
Douglas J Roberts-Wolfe, Peter W Kalivas
The development of new treatments for substance use disorders requires identification of targetable molecular mechanisms. Pathology in glutamatergic neurotransmission system in brain reward circuitry has been implicated in relapse to multiple classes of drugs. Glutamate transporter 1 (GLT-1) crucially regulates glutamatergic signaling by removing excess glutamate from the extrasynaptic space. The purpose of this review is to highlight the effects of addictive drug use on GLT-1 and glutamate uptake, and using GLT-1 as a target in addiction pharmacotherapy...
2015: CNS & Neurological Disorders Drug Targets
Deepmala, John Slattery, Nihit Kumar, Leanna Delhey, Michael Berk, Olivia Dean, Charles Spielholz, Richard Frye
N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy...
August 2015: Neuroscience and Biobehavioral Reviews
Ana Weiland, Steven Garcia, Lori A Knackstedt
Alcohol consumption and the reinstatement of alcohol-seeking rely on glutamate and GABA transmission. Modulating these neurotransmitters may be a viable treatment strategy to prevent alcohol relapse. N-acetylcysteine (NAC) and the antibiotic ceftriaxone (CEF) alter the glial reuptake and release of glutamate while the antibiotic cefazolin (CEFAZ) modulates GABA signaling without affecting glutamate. Here, we used the extinction-reinstatement model of relapse to test the ability of these compounds to attenuate the reinstatement of alcohol-seeking...
2015: Frontiers in Pharmacology
Ricardo Schneider, Carolina Ferreira Santos, Vanessa Clarimundo, Carla Dalmaz, Elaine Elisabetsky, Rosane Gomez
N-acetylcysteine (NAC), a glutamate-modulating agent with antioxidant and anti-inflammatory properties, has been considered as a potential anti-addictive drug. Beneficial effects were reported for cocaine, cannabis, and tobacco addicts, but the effect of NAC in alcoholics or in alcohol animal models is unknown. The aggravation of alcohol withdrawal symptoms, such as anxiety, has been associated with increased levels of serum corticosterone and leptin. Thus, the aim of this study was to assess the effects of NAC on anxiety, as well as corticosterone and leptin serum levels, after cessation of chronic alcohol treatment in rats...
May 2015: Alcohol
Robert D Winefield, Anthonius A M Heemskerk, Swetha Kaul, Todd D Williams, Michael J Caspers, Thomas E Prisinzano, Elinore F McCance-Katz, Craig E Lunte, Morris D Faiman
Disulfiram (DSF), a treatment for alcohol use disorders, has shown some clinical effectiveness in treating addiction to cocaine, nicotine, and pathological gambling. The mechanism of action of DSF for treating these addictions is unclear but it is unlikely to involve the inhibition of liver aldehyde dehydrogenase (ALDH2). DSF is a pro-drug and forms a number of metabolites, one of which is N-acetyl-S-(N,N-diethylcarbamoyl) cysteine (DETC-NAC). Here we describe a LCMS/MS method on a QQQ type instrument to quantify DETC-NAC in plasma and intracellular fluid from mammalian brain...
March 25, 2015: Journal of Pharmaceutical and Biomedical Analysis
Seyed Ghafur Mousavi, Mohammad Reza Sharbafchi, Mehrdad Salehi, Mohammad Peykanpour, Naeemeh Karimian Sichani, Mohammad Maracy
OBJECTIVE: Preclinical studies and early pilot clinical investigations have suggested that N-acetylcysteine (NAC) may be useful in treatment of methamphetamine (METH) dependence. The present study evaluated whether NAC would suppress craving to the METH. METHODS: In a double-blind, controlled crossover clinical trial, 32 METH-dependent volunteers were chosen to receive either NAC (1200 mg/day) or placebo, randomly. They were intervened in two four-week sessions...
January 2015: Archives of Iranian Medicine
Elson Asevedo, Ana C Mendes, Michael Berk, Elisa Brietzke
OBJECTIVE: To conduct the first systematic literature review of clinical trials of N-acetylcysteine (NAC) for the treatment of substance abuse disorders and addictive behaviors. METHODS: A search of the MEDLINE, Embase and PsycINFO databases was conducted. The inclusion criteria for the review were clinical trials that used NAC in the treatment of a disorder related to substance use and/or addictive behaviors, limited to texts in English, Spanish, or French. The selected studies were evaluated with respect to type of trial, sample size, diagnostic input, intervention, length of follow-up, outcome variables, and results...
April 2014: Revista Brasileira de Psiquiatria
Małgorzata Frankowska, Joanna Jastrzębska, Ewa Nowak, Magdalena Białko, Edmund Przegaliński, Małgorzata Filip
Depression and substance-abuse (e.g., cocaine) disorders are common concurrent diagnoses. In the present study, we combined bilateral olfactory bulbectomy (OBX) with a variety of procedures of intravenous cocaine self-administration and extinction/reinstatement in rats. We also investigated the effects of N-acetylcysteine (NAC) on rewarding and seeking behaviors for cocaine in OBX rats and compared the drug's effects in sham-operated control animals (SHAM). The occurrence of depressive symptoms before introduction to cocaine self-administration enhanced subsequent cocaine-seeking behaviors but did not significantly influence cocaine's rewarding properties or extinction training...
June 1, 2014: Behavioural Brain Research
Kathryn J Reissner, Cassandra D Gipson, Phuong K Tran, Lori A Knackstedt, Michael D Scofield, Peter W Kalivas
Both pre-clinical and clinical studies indicate that N-acetylcysteine (NAC) may be useful in treating relapse to addictive drug use. Cocaine self-administration in rats reduces both cystine-glutamate exchange and glutamate transport via GLT-1 in the nucleus accumbens, and NAC treatment normalizes these two glial processes critical for maintaining glutamate homeostasis. However, it is not known if one or both of these actions by NAC is needed to inhibit relapse to cocaine seeking. To determine whether the restoration of GLT-1 and/or cystine-glutamate exchange is required for NAC to inhibit cue-induced reinstatement of cocaine seeking, we utilized the rat self-administration/extinction/reinstatement model of cocaine relapse...
March 2015: Addiction Biology
Laura H Corbit, Billy C Chieng, Bernard W Balleine
Exposure to drugs of abuse can result in a loss of control over both drug- and nondrug-related actions by accelerating the transition from goal-directed to habitual control, an effect argued to reflect changes in glutamate homeostasis. Here we examined whether exposure to cocaine accelerates habit learning and used in vitro electrophysiology to investigate its effects on measures of synaptic plasticity in the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas critical for actions and habits, respectively...
July 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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