Methylene Blue is a molecule used medically as a treatment for a problem with the protein hemoglobin (methemogobinemia), for cyanide poisoning, and for treatment resistant vasodilatory shock. I know it, though, from its common use as a dye (counterstain) for tissue in anatomy preparations and in some conditions screening for tissue changes that might signal cancer (e.g. during colonoscopy). It really makes things blue!
So I was surprised to find that it is being touted in platforms including Reddit and TikToK as a treatment (or preventative) for neurodegeneration, depression, anxiety. Is this even safe? How likely is this to be actually effective, rather than just a great inducer of placebo effects?
“Off label” use
Due to effects on mitochrondria that may convey “neuroprotection” from oxidative stress or other neurodegenerative factors8,9 , some in the psychiatric pharmaceutical world (which is always looking for new drugs) are pushing this as the next new miracle drug. An advantage is that it is already approved for human clinical use, so it would not have to go through the FDA approval process. It can be used “off label”. For FDA approval, it would need to be shown that the drug is both effective and safe. Safe could be a problem.
Can it be an anti-depressant?
It has been suggested to be anti-depressant because it can block an enzyme called monoamine oxidase (MAO), and other drugs that do this have antidepressant actions. However, it can also cause a condition called “serotonin syndrome”, particularly when a person is also taking, or recently took, other antidepressant drugs10 . Serotonin syndrome is a life-threatening condition that can include diarrhea, fever, neurological dysfunction, and seizures.
Another concern is that clinically approved use of methylene blue is usually used for acute situations, rather than chronically as it would need to be for anti-depressant use or to protect against neurodegeneration. One obvious concern about this would be stress on kidneys from having to clear it, as well turning urine and soft tissues (like mouth) blue. But a study from 2023 looking at whether methylene blue actually improves brain metabolism and blood flow11 found to their surprise - just the opposite. Importantly, they used the roughly same dose that others have used to study memory enhancement.
Is it safe?
One big concern is that methylene blue is being touted as a supplement, and thus could/is ingested without any medical supervision. This is of particular concern because methylene blue is well known for its “hermetic effects”8 . This means that is has different, even opposite effects, depending on the dose. How carefully will people using it as a supplement be about using a safe dose?
It is also a “dirty” drug, in that has several different mechanisms of action on different systems, which means it is a high risk for side effects, potentially very bad side effects. This is probably why the mainstream pharmaceutic companies have not jumped on it.
There IS evidence that under the proper circumstances, methylene blue may have beneficial effects on the brain. But it is risky, and mainstream pharmaceutic companies are highly risk averse (unlike supplement companies, they can get sued).
In this case, I would say that risk averse is good