Trial reportBiological psychiatry2009
The role of cystine-glutamate exchange in nicotine dependence in rats and humans.
Trial report in Biological psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 173 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Imaging Framework for Testing GABAergic/Glutamatergic Drugs in Bipolar Alcoholics
Effectiveness of N-Acetylcysteine in Motivational Enhancement Therapy for Nicotine Addiction: Study on the Dopaminergic Pathways, Changes in Functional Connectivity of fMRI Bold, and Changes in Smoking Abstinence
Who cites it
173 citing papers in PubMed, 1 synthesis or guideline pooled it, 259 citations in OpenAlex.
- Effect of N-acetylcysteine on craving in substance use disorders (SUD): a meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2024Pooled it
- Clavulanic acid is associated with moderation of cigarette use in patients with cocaine use disorder: A post-hoc analysis.Drug and alcohol dependence · 2026Trial
- Evaluating N-acetylcysteine for early and end-of-treatment abstinence in adult cigarette smokers.Drug and alcohol dependence · 2021Trial
- N-acetylcysteine reduces cocaine-seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine-dependent individuals.Addiction biology · 2021Trial
- Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- The effect of N-acetylcysteine on alcohol use during a cannabis cessation trial.Drug and alcohol dependence · 2018Trial
- Alcohol use during a trial of N-acetylcysteine for adolescent marijuana cessation.Addictive behaviors · 2016Trial
- Zonisamide Reduces Withdrawal Symptoms But Does Not Enhance Varenicline-Induced Smoking Cessation.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016Trial
- The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.Drug and alcohol dependence · 2015Trial
- N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study.Redox report : communications in free radical research · 2015Trial
- An open-label pilot trial of N-acetylcysteine and varenicline in adult cigarette smokers.The American journal of drug and alcohol abuse · 2015Trial
- Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network.Contemporary clinical trials · 2014Trial
- Cigarette smoking during an N-acetylcysteine-assisted cannabis cessation trial in adolescents.The American journal of drug and alcohol abuse · 2014Trial
- Marijuana craving trajectories in an adolescent marijuana cessation pharmacotherapy trial.Addictive behaviors · 2013Trial
- A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents.The American journal of psychiatry · 2012Trial
- N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients: a randomized crossover magnetic resonance spectroscopy study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Trial
- N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial.Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)Trial
- A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence.The American journal on addictionsTrial
- N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study.The American journal on addictionsTrial
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
113 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe present study determined if, akin to cocaine, nicotine self-administration in rats induces adaptations in the expression of glutamate transporters and cystine-glutamate exchangers in brain nuclei implicated in reinforcement and if treating cigarette smokers with a drug that restores cystine-glutamate exchange affects the number of cigarettes smoked.
methodsRats self-administered nicotine intravenously for 12 hours/day or received nicotine through osmotic minipumps for 21 days. Somatic signs of withdrawal were measured and immunoblotting was performed 12 hours after the last nicotine exposure to determine if the catalytic subunit of the cystine-glutamate exchanger, xCT, or the glial glutamate transporter, GLT-1, were altered in the ventral tegmental area (VTA), nucleus accumbens, prefrontal cortex, or amygdala. For the smoking reduction study in humans, nicotine-dependent smokers were treated for 4 weeks with N-acetylcysteine (2400 mg daily) to promote cystine-glutamate exchange or placebo. Participants provided weekly ratings of withdrawal symptoms, craving, and carbon monoxide (CO) measurements and logged daily cigarette and alcohol use.
resultsRats receiving nicotine via self-administration or minipumps displayed somatic signs of withdrawal, but only nicotine self-administering rats showed decreased xCT expression in the nucleus accumbens and VTA and decreased GLT-1 expression in the nucleus accumbens. Human smokers treated with N-acetylcysteine reported a reduction in cigarettes smoked, and there was no effect of N-acetylcysteine on estimates of CO levels, craving, or withdrawal.
conclusionsThese results indicate that the cystine-glutamate exchanger and the glial glutamate transporter are downregulated after nicotine self-administration, and augmenting exchanger activity with N-acetylcysteine reduced the number of cigarettes smoked in nicotine-dependent individuals.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.