A single dose of a 150-year-old textile dye raised memory retrieval scores by 7% in a randomized, placebo-controlled human trial. Tony Huge has been using methylene blue on and off for a decade, and this video is his re-check of the literature: the memory study, the poison center data, the G6PD contraindication, the MAO-A mechanism that makes it an antidepressant in disguise, and why the internet’s daily dosing walks people into the serotonin toxicity band.
Video: Methylene Blue for the Brain? What the Human Studies Actually Show. Published September 14, 2026. Watch on YouTube.
What the video covers
- 00:00 The 7% result: 26 adults, double blind, 280 mg once, brain scans running.
- 01:00 What methylene blue is: Synthesized in 1876, the first synthetic compound reported to treat an infectious disease.
- 01:26 The FDA-approved use: Antidote for methemoglobinemia at 1 mg/kg IV.
- 01:44 Mitochondria: It picks up electrons and hands them off, and neurons are the hungriest cells you own.
- 02:07 The memory trial: Retrieval up 7% one hour later, with matching activity in attention and memory networks.
- 03:10 Poison center data: 185 cases over 24 years, 98% improved, side effects in 4.9%.
- 04:10 The dose reversal: Too much causes the same methemoglobinemia it treats, plus hemolysis.
- 04:38 G6PD deficiency: An absolute contraindication carried by over 400 million people, most never told.
- 05:39 Tony checks his genetics: No G6PD deficiency.
- 06:04 MAO-A: 200 times more selective for MAO-A than MAO-B; think of it as an MAOI that happens to be blue.
- 08:19 Serotonin syndrome: 50 published cases, all combined with a serotonergic antidepressant, one death, all at hospital IV doses.
- 09:52 Why online dosing is wrong: 0.5 to 3 mg/kg daily lands a 200 lb man inside the published toxicity range.
- 11:45 Long-term human trials: Six months of daily dosing improved mood scores but not cognition.
- 12:08 The Alzheimer’s cousin molecule: 8 mg a day performed as well as 200 in a phase 3 program that missed its endpoints.
- 14:21 Tony’s experience: Ten years in, the literature has not changed his dose.
Same molecule, same blood, opposite direction
Tony’s framing for the entire video is that methylene blue is not a supplement with a side effect. It is an approved hospital drug with a narrow window, and the only thing that changes between antidote and poison is the dose. Its approved use is as the antidote to methemoglobinemia, a state where hemoglobin gets locked into a form that cannot carry oxygen, at 1 mg/kg intravenously, repeatable once. Push the dose high enough and it causes the same methemoglobinemia it treats, and it starts rupturing red blood cells.
The reason it does anything in the brain is the same reason it works in the blood. Methylene blue picks up electrons and hands them off. At low concentrations it slots into mitochondria and supports the electron transport chain. Neurons are the most energy-hungry cells in the body, so that is where a mitochondrial helper shows up first.
The approved use has the best data. Tony cites a poison center series covering 24 years and 185 poisonings treated with methylene blue at a median 1 mg/kg: 98% of patients improved, side effects in 4.9%, and the two deaths came from the poison itself in patients the antidote could not reach in time. His point is that anyone calling methylene blue snake oil is arguing against a 98% hit rate. The open question is what happens when you change the dose and the purpose.
The 7% and what it does not prove
Tony cites the memory trial in detail: 26 healthy adults aged 22 to 62, randomized, double blind, placebo controlled, a single 280 mg oral dose (about 4 mg/kg), brain scans before and one hour after. Memory retrieval rose 7%, and the scans showed increased response in the attention network and in memory circuits across prefrontal, parietal, and occipital cortex while subjects worked. A second single-dose trial at 260 mg on fear extinction learning pointed the same way.
“The 7% came from one dosage measured one time. The daily habit built on top of that result is an extrapolation.”
Tony Huge, 03:00
That is the limitation in one sentence, and Tony returns to it repeatedly. The two long daily human trials he found were both in psychiatric patients: 300 mg a day for a year in a crossover, and 195 mg a day for six months in a proper randomized trial. In the second, depression and anxiety scores improved, but cognitive scores could not be separated from control. Six months of daily dosing did not raise the memory benefit everyone is chasing. He adds the Alzheimer’s data from a stabilized cousin molecule that reached phase 3 at 150 to 250 mg a day and missed both primary endpoints; buried in the company’s own data, 8 mg a day performed as well as 200. More was never better.
An MAOI that happens to be blue
The second mechanism is the one Tony thinks most users ignore. Methylene blue is a monoamine oxidase inhibitor, 200 times more selective for MAO-A than MAO-B, and its main metabolite azure B inhibits the same enzyme even harder. That MAOI effect is present at every dose, so even a small amount is doing something to brain neurotransmitters. Tony’s reframe: do not think of it as a dye with a side effect. Think of it as an antidepressant-class compound that is also blue.
That is why the serotonin syndrome warning exists. Tony cites a systematic review of 50 published cases of methylene blue serotonin syndrome. All 50 were in patients also taking a serotonergic antidepressant; only one died; and all came from high-dose IV use in hospitals, mostly around surgery. In a database of 249,131 surgical patients who received methylene blue, 10.14% were on a serotonin drug at the same time. His read is that the molecule is very safe on the totality of the data, with deaths rare and confined to the combination, but he asks the audience to consider how many biohackers on an SSRI are watching methylene blue videos.
Tony describes having entered the early range of serotonin syndrome himself while testing interactions at very low starting doses: agitation, heat like a fever, tight muscles, a physical inability to relax that he compares to his restless leg syndrome. He never reached a severe case because he keeps doses low, and he says that is the entire reason.
The genetic edge and the internet dose
G6PD deficiency is an absolute contraindication at any dose because those red blood cells cannot defend against oxidative stress. More than 400 million people carry it, most never told. Tony notes the literature keeps both halves honest: a published case of severe hemolysis in a patient with normal G6PD, hemoglobin down to 6.6, and a study where 74 men with a milder G6PD variant took 780 mg over three days with no hemolysis. The gene test tells you a lot but not everything. On camera, Tony checks his own genetic report for the first time in ten years of use and finds he does not carry the deficiency.
The dosing section is where he is most critical of his own community. The internet range is 0.5 to 3 mg/kg daily, which for a 200 lb man is 45 to 270 mg a day. Oral bioavailability is about 72%, so 270 mg swallowed puts roughly 2.8 mg/kg into the system, and the published serotonin toxicity cases sit at 1 to 8 mg/kg. The internet dose, in his words, walks you into the toxicity band and tells you to stay there every day. He has never taken the high end and sees no need to, since he gets benefits at much lower amounts and prefers the minimum effective dose.
Cheat Sheet Pivot
What Tony reported and what the studies used. He does not state his own dose in the video and says the platform would treat that as advice.
- The memory trial used a single 280 mg oral dose; the fear extinction trial used 260 mg once. Tony treats these as single-dose evidence, not a daily template.
- The approved antidote course is 1 mg/kg IV, repeatable once. There is no approved daily use.
- Tony takes it orally, sees no reason to inject at 72% bioavailability, and uses urine color as one gauge of his dose.
- He starts any new combination at the lowest possible dose specifically so that side effects show up small enough to read.
- He has stayed well below the internet’s daily range for ten years and says the current literature confirms rather than challenges that.
- He has a single exception: one higher-dose period, roughly 60% of the hospital IV dose, to treat a condition he declines to name, which he believes methylene blue resolved.
Methylene blue’s entry alongside the rest of the nootropic catalog is in the Miracle Molecules Cheat Sheet. For the mitochondrial mechanism in more depth, read Methylene Blue: The Forgotten Nootropic That Actually Boosts Mitochondria, and for how Tony has run it, see Methylene Blue Protocol: The Mitochondrial Enhancer Tony Huge Runs.
Where the evidence stops
Tony is direct that the strongest cognitive evidence is one dose in 26 people measured once, and that the only six-month randomized trial found no separable cognitive benefit. He explains the research gap the way he usually does: the molecule dates from 1876, nobody can own it, so nobody funds the trial, and the one company that wanted a piece of the chemistry had to invent a patentable version.
That leaves the daily-use case resting on anecdotal reports, including his own, which he says outright. His claim is that a compound with MAOI activity at every dose is doing something you can feel; whether that something is worth the risk of, in his phrase, uncharted biohacking territory is a question he leaves to the viewer and their doctor.
Keep going
Tony’s other methylene blue combination is covered in Methylene Blue + 5-Amino-1MQ: The Engineered NAD+ Stack. New companion articles reach the tonyhuge.is email list first, and the nootropic archive is at tonyhuge.is.