Methylene Blue

weak data

Also seen as: methylthioninium chloride, Basic Blue 9, MB

The Dose Guy’s verdict

Sep 1, 2026
6 sources

Low dose, low expectations. Methylene blue has a long clinical history and the hospital data is real, 11 randomized trials in shock show a mortality risk ratio of 0.60. But that is not why most people buy it. The nootropic community runs low oral doses for cognitive and mitochondrial benefits, and there the case is thinner. The bipolar trial found improvement in depression and anxiety but no effect on cognition, the endpoint the nootropic crowd actually cares about. The Alzheimer trials were a wash. If you came here for the brain boost, creatine and regular exercise have more behind them for a healthy person.

Would I take it?Maybe, low dose, low expectations.

What it is

Methylene blue is a 19th-century synthetic dye that turned out to be a drug. Clinically it is used as an antidote for methemoglobinemia and as a rescue in vasodilatory shock, where it tightens blood vessels by inhibiting nitric oxide synthase. The nootropic angle comes from a different property: at low doses, methylene blue acts as an alternative electron carrier in mitochondria, accepting electrons and cycling between oxidized and reduced forms, which can support energy production when the usual chain is stressed. It is also a potent reversible inhibitor of monoamine oxidase A, which means it boosts serotonin and norepinephrine availability, which is also why combining it with SSRIs or other serotonergic drugs risks serotonin toxicity.

What the research shows

Strong clinical evidence in hospital and surgical settings. The nootropic and cognitive evidence is thinner:

Across 11 randomized trials in shock, methylene blue cut mortality with a risk ratio of 0.60, 95% CI 0.43 to 0.84, p=0.003, and raised mean arterial pressure by 8.4 mmHg.J Clin Anesth 2024 · meta-analysis · 11 RCTs · n=556

In older noncardiac surgery patients, intravenous methylene blue at 2 mg/kg cut postoperative delirium from 24.2% to 7.3% and early cognitive dysfunction from 40.2% to 16.1%.J Clin Neurosci 2021 · open-label RCT · n=248

In lamotrigine-treated bipolar patients, 195 mg methylene blue daily improved residual depression and anxiety versus a 15 mg control dose over six months, but had no significant effect on cognitive symptoms.Br J Psychiatry 2017 · crossover RCT · n=37

Randomized trials of hydromethylthionine, a methylene blue derivative, found no effect on Alzheimer disease course at the tested doses.Clin Drug Investig 2020 · trial review

Methylene blue was a potent reversible inhibitor of human monoamine oxidase A. At reported intravenous concentrations, complete MAO-A inhibition was expected, the mechanism behind serotonin toxicity reports.Curr Clin Pharmacol 2007 · enzyme study

An evidence-based review found solid evidence to prohibit methylene blue in people with G6PD deficiency because of hemolytic risk.Drug Saf 2010 · evidence review

Realistic protocols

Low dose is the whole game for the nootropic use. The mitochondrial electron-carrier effect works at low concentrations, and higher doses flip it, becoming pro-oxidant instead of protective. The community runs 0.5 to 1 mg/kg orally, which for a 70 kg person means roughly 35 to 70 mg once in the morning. Start at the low end. Take it with food. The positive hospital trials used higher doses, 2 mg/kg IV for delirium and 195 mg daily for bipolar symptoms, but those were supervised clinical settings, not self-experimentation, and the nootropic community deliberately stays below that range for the mitochondrial benefit without the pro-oxidant flip.

Two hard rules. First, do not combine methylene blue with any serotonergic drug: SSRIs, SNRIs, MAOIs, tramadol, triptans. Methylene blue is a potent reversible MAO-A inhibitor, and at reported intravenous concentrations it completely inhibits the enzyme. Whether a 35 mg oral dose reaches those concentrations is less clear, but the serotonin toxicity risk is not worth testing on yourself. If you are on an antidepressant, this is not for you until you are off it and cleared. Second, if you have G6PD deficiency or do not know your status, do not take it. The hemolytic reaction is well documented and avoidable.

Start0.5 mg/kgAbout 35 mg for a 70 kg person. Morning, with food.

Hold0.5–1 mg/kgStay low. The mitochondrial benefit inverts at higher doses.

Ceiling1 mg/kgThe nootropic ceiling. Hospital trials go higher under supervision.

Side effects

Most side effects are dose-related and manageable at low doses:

commonBlue-green urine and stool. Blue tongue and lips at higher doses. Expected pharmacology, not a side effect.

commonMild nausea and headache at higher oral doses, usually dose-related and self-limiting.

monitorSerotonin toxicity when combined with SSRIs, SNRIs, or other serotonergic drugs. Methylene blue is a potent MAO-A inhibitor. This is the interaction that can hurt you.

monitorHemolytic anemia in G6PD-deficient individuals. Screen before starting.