The Serotonin Syndrome Risk
Methylene blue
Also known as Methylthioninium chloride · ProvayBlue
At a glance
- What it is
- Not a peptide. Approved for methemoglobinemia, and it carries a boxed warning.
- Evidence
- Clinical trialsHow the tiers workMethylene blue has an approved US label for acquired methemoglobinemia and nothing else. Why this tier
- Half-life
- Approximately 24 hours
- Routes
- Intravenous
- Category
- Cognitive, Support
- WADA
- We do not state a status
Not schedulable in Claritide. Our sources publish no dosing figure for Methylene blue, so there is nothing to build a schedule from.
Why this tier
Methylene blue has an approved US label for acquired methemoglobinemia and nothing else. Human neuroimaging work suggests low doses may modulate brain activity during attention and short-term memory tasks, and may improve memory consolidation and retrieval in healthy adults. That is aggregator-tier synthesis, and it is explicitly not proven or recommended for routine nootropic, longevity or anti-ageing use. We publish no community oral dose: the interaction profile makes an unsupervised figure indefensible.
What it is
Methylene blue is not a peptide. It is a small-molecule dye with one approved indication, acquired methemoglobinemia, and it is in this library because it appears in almost every nootropic and longevity stack our users will encounter, and because it carries the most dangerous drug interaction in our entire source set. It has a boxed warning for serious or fatal serotonin syndrome when combined with serotonergic drugs and opioids, and it is contraindicated in G6PD deficiency.
How it works
At the approved indication, methylene blue is a redox agent: it acts as an electron acceptor in the reduction of methaemoglobin back to functional haemoglobin, restoring the blood’s ability to carry oxygen. The nootropic interest comes from a different property of the same chemistry: at low concentrations it can cycle electrons in mitochondria, acting as an alternative electron carrier, which is the basis for claims about brain energy metabolism. The dangerous property is a third one: methylene blue is a potent monoamine oxidase inhibitor. That is the mechanism behind the boxed warning, and it is not a niche theoretical concern. It is why combining it with an SSRI can be fatal.
Commonly researched ranges
- Label dose · acquired methemoglobinemia1 mg
The repeat dose applies if methaemoglobin remains above 30% or symptoms persist. This is a hospital medication given by a clinician, and it is the only dosing on the label. Read the frequency before the number: 1 mg is per kilogram of body weight, so it is about 70 mg in a 70 kg adult. Claritide publishes no dose figure to choose for methylene blue for exactly that reason: a weight-relative figure is not an amount anyone can draw.
| Phase | Amount | Frequency | Timing | Note |
|---|---|---|---|---|
| Label dose · acquired methemoglobinemia | 1 mg | Per kilogram of body weight, intravenously over 5–30 minutes; may repeat once at 1 hour | Not established in available literature | The repeat dose applies if methaemoglobin remains above 30% or symptoms persist. This is a hospital medication given by a clinician, and it is the only dosing on the label. Read the frequency before the number: 1 mg is per kilogram of body weight, so it is about 70 mg in a 70 kg adult. Claritide publishes no dose figure to choose for methylene blue for exactly that reason: a weight-relative figure is not an amount anyone can draw. |
- Cycle guidance
- Not cycled. The approved use is acute treatment of a specific blood disorder, not an ongoing regimen.
- Goals
- Cognition, Energy
Where this sits with the FDA
FDA-approved drug product (ProvayBlue)
Approved for acquired methemoglobinemia in paediatric and adult patients. Nothing else is approved. The oral tablets and tinctures sold for cognition are a different supply chain from the approved intravenous product and carry the same interaction profile.
Primary sourceHow it got here
- 20 October 2011
FDA drug safety communication on serious central nervous system reactions when methylene blue is given to patients taking serotonergic psychiatric medications.
WADA status
Not named on the 2026 Prohibited List. Methylene blue holds a US marketing authorisation, so the S0 catch-all does not obviously capture it. We could not determine a classification and do not state one.
We looked and could not resolve it. This is not the same as "not prohibited". Treat it as unresolved and check with your federation before competing.
There is nothing to mix
Not applicable. None of the published routes for this compound take a diluent, so there is no concentration to calculate and no beyond-use window to track.
Week by week
Not established in available literature.
Side effects
Common
- Blue-green discoloration of urine and skin
Uncommon
- Haemolytic anaemia
Rare
- Serotonin syndrome
Contraindications and interactions
Do not use if
- G6PD deficiency: contraindicated on the label because of haemolytic anaemia risk
- Severe hypersensitivity to methylene blue
- Serotonergic medication of any kind, including SSRIs, SNRIs, MAOIs and opioids: this is a boxed warning, not a caution
- Pregnancy: animal studies showed developmental toxicity at 16 to 32 times the clinical dose, and intra-amniotic exposure has caused neonatal intestinal atresia and fetal death
Interactions
- SSRIs, SNRIs and other serotonergic antidepressantsavoid
Methylene blue is a potent monoamine oxidase inhibitor. The combination can cause serious or fatal serotonin syndrome. This is the compound’s boxed warning.
- MAOIsavoid
Additive monoamine oxidase inhibition. Avoid.
- Opioidsavoid
Named alongside serotonergic drugs in the boxed warning. Several opioids have serotonergic activity of their own.
Absence from this list does NOT mean safety. It means lack of research.
Storage and cost
- Storage
- The approved product is a manufactured intravenous solution handled in a clinical setting. There is no home reconstitution, no diluent pairing and no beyond-use window for a user to track.
- Cost
- Not established in available literature
Methylene blue in full
Why a dye is in a peptide library
Methylene blue is not a peptide. It is a small-molecule dye first synthesised in the nineteenth century.
It is here because it is in nearly every nootropic and longevity stack our users will meet, and because it carries the most dangerous drug interaction in our entire source set. Excluding it on taxonomic grounds would be a decision to let people get hurt tidily.
The boxed warning
Verbatim from the label: "May cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids."
The mechanism is that methylene blue is a potent monoamine oxidase inhibitor. MAO is the enzyme that clears serotonin; block it while something else is raising serotonin and levels can climb into a syndrome that ranges from tremor and agitation to hyperthermia, rigidity and death.
The drugs this covers are not exotic. SSRIs and SNRIs, the most-prescribed antidepressant classes in the world. MAOIs. Opioids, several of which are serotonergic themselves. FDA issued a drug safety communication about this on 20 October 2011, noting that adverse events typically occurred at intravenous doses of 1 to 8 mg/kg during parathyroid surgery, where methylene blue is used as a tissue dye.
A person taking an SSRI who adds methylene blue from a nootropic stack has assembled a documented, potentially fatal interaction without either product mentioning the other.
Contraindicated in G6PD deficiency
Glucose-6-phosphate dehydrogenase deficiency is the most common enzyme deficiency in the world, affecting hundreds of millions of people, and many carriers do not know they have it. Methylene blue is contraindicated in G6PD deficiency because it causes haemolytic anaemia, and haemolysis risk exists in all patients, with Heinz bodies and elevated bilirubin as the markers.
Embryo-fetal toxicity
Developmental toxicity has been shown in animals at 16 to 32 times the clinical dose. Intra-amniotic exposure in humans has caused neonatal intestinal atresia and fetal death.
What it is approved for
Acquired methemoglobinemia, in adults and children. That is the whole label.
Methaemoglobin is haemoglobin whose iron has been oxidised so it can no longer carry oxygen; certain drugs and chemicals cause it. Methylene blue acts as an electron acceptor that reduces it back to functional haemoglobin. The dose is 1 mg/kg intravenously over 5 to 30 minutes, repeated once at one hour if methaemoglobin remains above 30% or symptoms persist. Half-life is about 24 hours.
That is a hospital treatment for an acute emergency. It is not a regimen.
The nootropic use
Human neuroimaging suggests low doses may modulate brain activity during attention and short-term memory tasks, and may improve memory consolidation and retrieval in healthy adults. That summary is aggregator-tier and it is explicitly not proven or recommended for routine nootropic, longevity or anti-ageing use.
We publish no community oral dose. Not because the figures are hard to find, but because a compound with a boxed warning for a fatal interaction against two of the most widely prescribed drug classes on earth should not have an unsupervised number attached to it on a page like this. If you want to use methylene blue for cognition, the conversation to have is with a prescriber who knows your full medication list, starting with whether anything on it touches serotonin.
Sources
Every record in this library is free to read, and it stays free. Your own schedule, vials and log live in the app: Claritide for iPhone.