Methylene blue is a potent inhibitor of MAO-A, which explains serotonin toxicity with SSRIs
A lab study on purified human enzyme found methylene blue is a potent, tight-binding inhibitor of monoamine oxidase A. At reported IV concentrations, MAO-A would be completely inhibited, accounting for serotonin toxicity with SSRIs.
We have not finished checking this source. No judgement either way. how we score evidence
Caveat on this rating: In vitro enzyme kinetics; explains a mechanism but gives no clinical rate, and its concentration argument concerns IV dosing.
The laboratory study that explained why methylene blue behaves like an MAOI.
Significant findings
Ramsay, Dunford and Gillman (British Journal of Pharmacology, 2007) set out to test a prediction: that methylene blue, a dye in clinical use that had been reported to precipitate serotonin toxicity in patients on SSRIs, does so by inhibiting monoamine oxidase. Using purified human MAO in kinetic assays, they found that "MB was a potent (tight binding) inhibitor for MAO A. It also inhibited MAO B but at much higher concentration."
Their conclusion: "MB is a potent reversible inhibitor of MAO A with implications for gut uptake of amines when administered orally. At concentrations reported in the literature after intravenous administration, MAO B would be partially inhibited but MAO A would be completely inhibited. This inhibition of MAO A would be expected to lead to perturbations of 5-hydroxytryptamine metabolism and hence account for ST occurring when administered to patients on SSRI treatment."
The other direction
This is enzyme work in a test tube, not a study of patients; it explains a mechanism and does not measure how often toxicity happens at a given dose or route. Its concentration argument is about intravenous doses. The authors raise oral dosing as a separate question about absorption from the gut, and the FDA later said the risk by oral routes was not known.
What this does not show
It does not show that any particular dose by mouth is safe or unsafe with an antidepressant. Methylene blue has no approved psychiatric use. It is not a reason to stop any medication.
Worth asking
If methylene blue blocks the same enzyme as an MAOI, what does that mean for the other medicines I take?
Source
Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction — Ramsay RR, Dunford C, Gillman PK (2007)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1038/sj.bjp.0707430
DOI: 10.1038/sj.bjp.0707430
How this was scored
- Study design
- not recorded
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
We have not finished checking this source, so there is no scoring to show yet. “We have not checked this yet” and “this is disputed” are different statements, so no scored band is shown rather than a low one.
Read the full scoring rubric, including what it can't tell you.
Published October 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "not yet assessed". We have not finished checking this source. No judgement either way. One caveat travels with that badge: In vitro enzyme kinetics; explains a mechanism but gives no clinical rate, and its concentration argument concerns IV dosing. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction — Ramsay RR, Dunford C, Gillman PK (2007). Published in: Reputable peer-reviewed journal. DOI: 10.1038/sj.bjp.0707430. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.