Methylene Blue

What it is

Methylene blue is one of the oldest synthetic drugs - a deep blue phenothiazine dye first made in 1876 and still FDA-approved today to treat methemoglobinemia, a blood disorder, given intravenously in a hospital. In the last few years it has been rediscovered as a longevity and 'nootropic' supplement, taken in low oral doses for claimed benefits to energy, focus, and mood. The honest state of the evidence: one well-run single-dose study found a small, measurable memory effect from an oral dose, but ongoing low-dose 'microdosing' benefits are not clinically established - most of that is community experience and cell or animal biology, not human trials. Two things make methylene blue genuinely different from a typical supplement, and both can hurt you if you get them wrong. First, it is a strong MAO-A inhibitor, so mixing it with common antidepressants (SSRIs, SNRIs, MAOIs) or other serotonergic drugs can cause serotonin syndrome - a reaction the FDA flags in a boxed warning. Second, it is sold in wildly different grades - pharmaceutical (USP), 'research chemical,' and aquarium or industrial - and only the pharmaceutical grade is made to a purity standard fit for a human body. This page lays out the numbers, the grades, and the interactions, each tied to a real source.

Dose ranges

Study-backed ranges carry a source you can open. Community ranges are widely reported but not clinically established - treat them as what people do, not as advice.

Storage

Tools for Methylene Blue

Interactions & cautions

This is the single most important thing to know about methylene blue. It is a potent, reversible inhibitor of monoamine oxidase A (MAO-A) - the enzyme that clears serotonin - with an inhibition constant around 27 nM, which is why it behaves like a strong MAOI even though it is sold as a dye. Combined with drugs that raise serotonin, it can trigger serotonin syndrome, a potentially fatal reaction. The current FDA-approved label carries a boxed warning that methylene blue 'may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids,' and names SSRIs, SNRIs, MAOIs, opioids, and specific drugs including bupropion, buspirone, clomipramine, mirtazapine, linezolid, and dextromethorphan. Severe toxicity has been reported at IV doses as low as 1 mg/kg. Separately, methylene blue is contraindicated in G6PD deficiency (hemolysis risk) and in pregnancy. If you take any antidepressant or serotonergic medication, do not combine it with methylene blue without a doctor's guidance - run your list through the interaction checker and talk to your prescriber.

Questions people ask

Sources

1. [1]PROVAYBLUE (methylene blue) injection - FDA-approved label (DailyMed)labelFDA-approved indication (methemoglobinemia), 1 mg/kg IV dosing, the boxed warning on serotonergic/MAOI interaction and the named drug classes, 0.5% (5 mg/mL) concentration, a stated half-life of about 24 hours, and storage and light-protection instructions.
2. [2]Methylene Blue Injection, USP 1% - FDA label (DailyMed)labelConfirms a 1% solution equals 10 mg/mL, a 0.1-0.2 mL/kg dosing volume, and the MAOI / serotonergic-drug warning language.
3. [3]USP-NF Methylene Blue monographregulatoryThe USP monograph exists and specifies a purity of 97.0 to 103.0% methylene blue on a dried basis - the standard that defines pharmaceutical (USP) grade.
4. [4]Peter C, et al. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol. 2000 PMID 10952480studyTerminal half-life of about 5.25 hours after IV dosing, and substantially lower oral bioavailability than IV.
5. [5]Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A). Br J Pharmacol. 2007studyMethylene blue is a potent, reversible MAO-A inhibitor (Ki about 27 nM), roughly 200-fold more potent at MAO-A than MAO-B - the mechanistic basis for its serotonin-toxicity risk.
6. [6]Methemoglobinemia (StatPearls, NCBI Bookshelf NBK537317)reviewThe 1-2 mg/kg IV clinical dosing range, the G6PD hemolysis threshold above 5 mg/kg, and the MAOI interaction caution.
7. [7]McMillan et al. Prevalence of Serotonergic Drug Use in Patients Exposed to Perioperative Methylene Blue: A Cross-Sectional Study. Cureus. 2025 (PMC12017462)studyConfirms the FDA black-box warning, that MAO-A inhibition is reached at IV doses as low as 0.75 mg/kg, and that a meaningful share of surgical methylene-blue patients are concurrently on serotonergic drugs.
8. [8]Rodriguez P, et al. Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain. Radiology. 2016 PMID 27351678studyA single oral 280 mg dose produced measurable brain-imaging changes and a 7% increase in correct memory-retrieval responses vs placebo in 26 healthy adults - one acute-dose RCT, not a chronic protocol.
9. [9]Gillman PK. CNS toxicity involving methylene blue: the exemplar for predicting drug interactions that precipitate serotonin toxicity. J Psychopharmacol. 2011reviewTies the dose to the risk: 0.75 mg/kg IV produced MAO-A-inhibiting plasma levels, and severe serotonin toxicity has been reported at doses as low as 1 mg/kg.
10. [10]Methylene Blue-Induced Serotonin Toxicity: Case Files (PMC10774363)studyDocuments real serotonin-toxicity cases and the spread of reported half-life figures (about 5.5, 14, and 24 hours across sources).
11. [11]PubChem CID 6099 - Methylene Blue (NIH/NLM)referenceChemical identity: methylthioninium chloride, CAS 61-73-4, molecular formula C16H18ClN3S, and recognized synonyms.
12. [12]WinAging - Heavy metals in reagent vs USP grade methylene blue (community)communityCommunity-level claims that non-USP grades can carry heavy-metal contamination. Directionally consistent with vendor guidance but not backed by independent lab testing - labeled community, not established fact.
13. [13]Nootropics Expert - Methylene Blue (community)communityCommunity-reported oral 'nootropic' dosing range of roughly 0.5-4 mg/kg, presented as self-styled protocol, not clinical guidance.