Trial reportThe Journal of clinical psychiatry2016
A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders.
Trial report in The Journal of clinical psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02499029 (Glial Regulators for Treating Comorbid Posttraumatic Stress and Substance Abuse Disorders), which is not on this map. Cited by 58 papers, 7 of them syntheses 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.
Glial Regulators for Treating Comorbid Posttraumatic Stress and Substance Abuse Disorders
Who cites it
58 citing papers in PubMed, 7 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- N-acetylcysteine for patients with alcohol use disorder, post-traumatic stress disorder, and their co-occurrence: a systematic review of placebo-controlled randomized trials.BMC psychiatry · 2026Pooled it
- N-acetylcysteine as a treatment for substance use cravings: A meta-analysis.Addiction biology · 2024Pooled it
- Project harmony: A systematic review and network meta-analysis of psychotherapy and pharmacologic trials for comorbid posttraumatic stress, alcohol, and other drug use disorders.Psychological bulletin · 2024Pooled it
- Effect of N-acetylcysteine on craving in substance use disorders (SUD): a meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2024Pooled it
- Project Harmony: A Meta-Analysis With Individual Patient Data on Behavioral and Pharmacologic Trials for Comorbid Posttraumatic Stress and Alcohol or Other Drug Use Disorders.The American journal of psychiatry · 2023Pooled it
- Pharmacotherapy for post traumatic stress disorder (PTSD).The Cochrane database of systematic reviews · 2022Pooled it
- Comparative Efficacy and Acceptability of Pharmaceutical Management for Adults With Post-Traumatic Stress Disorder: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Pooled it
- A Randomized Controlled Trial of N-acetylcysteine for Adolescent and Young Adult Alcohol Use Disorder.Journal of the American Academy of Child and Adolescent Psychiatry · 2026Trial
- Evaluating N-acetylcysteine for early and end-of-treatment abstinence in adult cigarette smokers.Drug and alcohol dependence · 2021Trial
- Randomized Controlled Trial of Riluzole Augmentation for Posttraumatic Stress Disorder: Efficacy of a Glutamatergic Modulator for Antidepressant-Resistant Symptoms.The Journal of clinical psychiatry · 2020Trial
- A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo.BMC medicine · 2019Trial
- The effect of N-acetylcysteine on alcohol use during a cannabis cessation trial.Drug and alcohol dependence · 2018Trial
- Complementary and integrative health interventions for PTSD in Veterans and family members: A rapid systematic review and meta-analysis.Journal of military, veteran and family health · 2026Article
- From Stress to Substance Use Disorders: The Expanding Role of Microglia-Astrocyte Crosstalk in Neuroimmune and Glutamate Alterations in the Nucleus Accumbens.International journal of molecular sciences · 2025Review
- How changes in post-traumatic stress disorder (PTSD) severity mediate substance use disorder (SUD) severity during and after treatment for co-occurring PTSD and SUD: Results from Project Harmony.Addiction (Abingdon, England) · 2025Observational
- Effects of N-acetylcysteine treatment on frontal glutamate and GABA levels and associations with drinking quantity in people with co-occurring posttraumatic stress disorder and alcohol use disorder.Psychopharmacology · 2025Article
- Review
- Brain glutathione levels and associations with recent drinking in treatment-naïve individuals with alcohol use disorder versus light drinkers.Drug and alcohol dependence · 2025Article
- Similarities and Differences in Neurobiology.Advances in experimental medicine and biology · 2025Review
- Exploring the potential link between ΔFosB andActa neuropsychiatrica · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe antioxidant N-acetylcysteine is being increasingly investigated as a therapeutic agent in the treatment of substance use disorders (SUDs). This study explored the efficacy of N-acetylcysteine in the treatment of posttraumatic stress disorder (PTSD), which frequently co-occurs with SUD and shares impaired prefrontal cortex regulation of basal ganglia circuitry, in particular at glutamate synapses in the nucleus accumbens.
methodsVeterans with PTSD and SUD per DSM-IV criteria (N = 35) were randomly assigned to receive a double-blind, 8-week course of N-acetylcysteine (2,400 mg/d) or placebo plus cognitive-behavioral therapy for SUD (between March 2013 and April 2014). Primary outcome measures included PTSD symptoms (Clinician-Administered PTSD Scale, PTSD Checklist-Military) and craving (Visual Analog Scale). Substance use and depression were also assessed.
resultsParticipants treated with N-acetylcysteine compared to placebo evidenced significant improvements in PTSD symptoms, craving, and depression (β values < -0.33; P values < .05). Substance use was low for both groups, and no significant between-group differences were observed. N-acetylcysteine was well tolerated, and retention was high.
conclusionsThis is the first randomized controlled trial to investigate N-acetylcysteine as a pharmacologic treatment for PTSD and SUD. Although preliminary, the findings provide initial support for the use of N-acetylcysteine in combination with psychotherapy among individuals with co-occurring PTSD and SUD.
trial registrationClinicalTrials.gov identifier: NCT02499029.
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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.