Methylene blue modulates functional connectivity in the human brain

Brain Imaging Behav. 2017 Jun;11(3):640-648. doi: 10.1007/s11682-016-9541-6.


Methylene blue USP (MB) is a FDA-grandfathered drug used in clinics to treat methemoglobinemia, carbon monoxide poisoning and cyanide poisoning that has been shown to increase fMRI evoked blood oxygenation level dependent (BOLD) response in rodents. Low dose MB also has memory enhancing effect in rodents and humans. However, the neural correlates of the effects of MB in the human brain are unknown. We tested the hypothesis that a single low oral dose of MB modulates the functional connectivity of neural networks in healthy adults. Task-based and task-free fMRI were performed before and one hour after MB or placebo administration utilizing a randomized, double-blinded, placebo-controlled design. MB administration was associated with a reduction in cerebral blood flow in a task-related network during a visuomotor task, and with stronger resting-state functional connectivity in multiple regions linking perception and memory functions. These findings demonstrate for the first time that low-dose MB can modulate task-related and resting-state neural networks in the human brain. These neuroimaging findings support further investigations in healthy and disease populations.

Keywords: Default mode network; Evoked response; Functional connectivity; Methylene blue; Multimodal fMRI.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / physiology
  • Brain Mapping
  • Cerebrovascular Circulation / drug effects
  • Double-Blind Method
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Methylene Blue / pharmacology*
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neuropsychological Tests
  • Psychotropic Drugs / pharmacology*
  • Rest
  • Visual Perception / drug effects
  • Visual Perception / physiology


  • Psychotropic Drugs
  • Methylene Blue