Trial reportThe American journal of psychiatry2014
Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia.
Trial report in The American journal of psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02380573 (Cognitive and Functional Connectivity Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease), which is not on this map. Cited by 30 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.
Cognitive and Functional Connectivity Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Evaluating the safety of oral methylene blue during swallowing assessment: a systematic review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2021Pooled it
- Dose Timing of D-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder: A Randomized Clinical Trial.JAMA network open · 2020Trial
- L-DOPA improves extinction memory retrieval after successful fear extinction.Psychopharmacology · 2019Trial
- Measuring fear change within exposures: Functionally-defined habituation predicts outcome in three randomized controlled trials for pediatric OCD.Journal of consulting and clinical psychology · 2018Trial
- Methylene blue modulates functional connectivity in the human brain.Brain imaging and behavior · 2017Trial
- Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.Radiology · 2016Trial
- Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy.Behaviour research and therapy · 2016Trial
- Transcranial Laser Stimulation as Neuroenhancement for Attention Bias Modification in Adults with Elevated Depression Symptoms.Brain stimulationTrial
- Enhancing the Efficacy of Exposure Therapy: Translation of Pharmacological Augmentation of Fear Extinction.Annual review of clinical psychology · 2026Review
- The Emerging Role of Brain Mitochondria in Fear and Anxiety.Current topics in behavioral neurosciences · 2025Review
- The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Review
- Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation.Neuroscience and biobehavioral reviews · 2023Review
- Enhancing Psychological Interventions for Post-Traumatic Stress Disorder (PTSD) Treatment with Memory Influencing Drugs.Current neuropharmacology · 2023Review
- Understanding Human Fear Extinction: Insights from Psychophysiology.Current topics in behavioral neurosciences · 2023Article
- The elegant complexity of fear in non-human animals.Emerging topics in life sciences · 2022Article
- Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress.Frontiers in human neuroscience · 2021Article
- Methylene Blue Preserves Cytochrome Oxidase Activity and Prevents Neurodegeneration and Memory Impairment in Rats With Chronic Cerebral Hypoperfusion.Frontiers in cellular neuroscience · 2020Article
- Recent developments in the intervention of specific phobia among adults: a rapid review.F1000Research · 2020Review
- Methylene Blue in the Treatment of Neuropsychiatric Disorders.CNS drugs · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectivePreclinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. The authors report on the first controlled experiment to examine the memory-enhancing effects of posttraining methylene blue administration on retention of fear extinction and contextual memory following fear extinction training.
methodAdult participants displaying marked claustrophobic fear were randomly assigned to double-blind administration of 260 mg of methylene blue (N=23) or administration of placebo (N=19) immediately following six 5-minute extinction trials in an enclosed chamber. Retesting occurred 1 month later to assess fear renewal as indexed by peak fear during exposure to a nontraining chamber, with the prediction that the effects of methylene blue would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive-enhancing effects of methylene blue independent of its effects on fear attenuation.
resultsConsistent with predictions, participants displaying low end fear posttraining showed significantly less fear at the 1-month follow-up if they received methylene blue posttraining compared with placebo. In contrast, participants displaying moderate to high levels of posttraining fear tended to fare worse at the follow-up if they received methylene blue posttraining. Methylene blue's enhancement of contextual memory was unrelated to initial or posttraining claustrophobic fear.
conclusionsMethylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session.
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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.