Methylene Blue
Methylthioninium chloride
Mitochondrial electron donor and nootropic
About
A synthetic phenothiazine dye and small molecule (not a peptide) with over 130 years of medical use. FDA-approved as injectable ProvayBlue for acquired methemoglobinemia. At low oral doses it acts as an alternative electron carrier in the mitochondrial electron transport chain and a reversible MAO-A inhibitor, driving interest as a nootropic for attention, memory, and mitochondrial support. Sold as ready-to-use oral liquid drops; serotonin syndrome risk with antidepressants is the dominant safety concern.
Mechanism
Bypasses dysfunctional complexes I and III by donating electrons directly to cytochrome c oxidase, boosting mitochondrial ATP output. Inhibits monoamine oxidase A, raising serotonin and dopamine. At high doses paradoxically generates methemoglobin; at low doses reduces it.
Dosage
When to take: Morning or early afternoon to avoid sleep disruption from mild stimulation. Take with food to reduce stomach upset. A 1% solution delivers ~0.5 mg per drop; a 2% solution ~1 mg per drop — verify concentration before dosing.
Reconstitution
Vial size (mg): N/A · BAC water (mL): N/A · Concentration: N/A
Oral compound — no reconstitution needed.
Benefits
- Improved sustained attention and short-term memory in fMRI studies
- Supports mitochondrial ATP synthesis via electron shuttle
- Mild mood elevation (MAO-A inhibition)
- Neuroprotective potential in preclinical models
- FDA-approved treatment for methemoglobinemia
Side effects
- Blue-green urine and stool (expected)
- Nausea, abdominal discomfort, headache
- Mild insomnia if dosed late
- Tongue and tooth staining (rinse mouth after sublingual use)
- Dizziness at higher doses
Gender notes
Cautions
- G6PD deficiency (hemolysis risk)
- Pregnancy (fetal harm risk)
- Concurrent SSRIs, SNRIs, MAOIs, or other serotonergic drugs — serotonin syndrome emergency
- Severe renal impairment
- Breastfeeding (unknown safety)
Research
- Multimodal randomized functional MR imaging of the effects of methylene blue in the human brain
Radiology · 2016
RCT in 26 healthy adults — single 280 mg oral dose increased fMRI activity in prefrontal and parietal cortex during memory tasks and improved retrieval by 7%.
- Methylene blue modulates functional connectivity in the human brain
Brain Imaging and Behavior · 2016
Resting-state and task-based fMRI study showing low-dose methylene blue modulates default mode and attention network connectivity.
- Methylene blue counteracts age-related cognitive impairment in mice and humans
Neurobiology of Aging · 2017
Preclinical-to-clinical translation study supporting mitochondrial mechanism of cognitive enhancement.