methylene blue nootropic

Methylene Blue

David Tomen
Author:
David Tomen
Jill Corleone, RD
Fact Checked:
Jill Corleone, RD
18 minute read
Methylene Blue boosts mitochondrial energy, is anti-aging, and improves mood and memory

Key Takeaways

  1. Methylene Blue, a synthetic compound, is used as a nootropic to enhance memory, mood, and longevity.
  2. It improves mitochondrial function and respiration in the brain, positively impacting memory and mood.
  3. Methylene Blue shows promise in treating neurological disorders such as mild cognitive impairment, Alzheimer’s, and Parkinson’s disease.
  4. It acts as an antioxidant, increases brain cell lifespan, and positively affects neurotransmitters.
  5. Methylene Blue dosage recommendation is 0.5 – 4 mg/kg of body weight per day.

 

Methylene Blue (methylthioninium chloride) is a synthetic compound used as a nootropic to increase memory, mood and longevity.

Soon after Methylene Blue was synthesized a blue dye for textiles in the late 1800’s, it became the first synthetic drug to be used in humans. It was used for the treatment of malaria.

In the early 20th century, psychiatrists were using Methylene Blue in the experimental treatment of schizophrenia.[i]

Methylene Blue is currently being studied as potential therapy for mild cognitive impairment, Alzheimer’s and Parkinson’s disease, and other neurodegenerative disorders. All sharing a common problem with mitochondrial function.

Your brain’s neurons rely almost entirely on mitochondria-derived energy. Failure of mitochondrial function can affect the rest of your body. But it’s particularly detrimental to your brain.

This is where Methylene Blue steps in as possibly one of the most important anti-aging and neurological disease preventing nootropics we have available today.

As a nootropic, Methylene Blue quickly crosses the blood-brain barrier. It improves mitochondrial efficiency and respiration, acts as an antioxidant, and increases brain cell lifespan. Resulting in improved memory and mood.

Here we’ll dive into over 140 years of research on how Methylene Blue helps your brain.

Methylene Blue helps:

  • Neurotransmitters: Methylene Blue inhibits monoamine oxidase and acetylcholinesterase activity which increases levels of catecholamines and acetylcholine. And boosts serotonin and norepinephrine affecting anxiety, depression and memory.
  • Mitochondrial Energy: Methylene Blue assists brain cell respiration by increasing oxygen. And donating electrons to the electron transport chain within mitochondria. This same process is used to create ATP within mitochondria from the food you eat. So MB contributes to this energy-production process in place of the nutrients you get from your food. Increasing cellular energy positively effects mood and memory.
  • Neuroprotectant: Methylene Blue is a potent antioxidant. Reactive oxygen species are produced inside mitochondria. The first free radical that is formed inside a cell is superoxide. MB will bind to superoxide and reduce it to water. It stops the oxidative cascade at its very beginning. Before it gets a chance to do damage.

Overview

Methylene Blue (methylthioninium chloride) was first synthesized in 1876 by German chemist Heinrich Caro at BASF as an aniline-based dye for cotton staining.

The chemical structure of Methylene Blue
Methylene Blue

In 1891, German physician and Noble Prize recipient Paul Ehrlich pioneered the use of Methylene Blue for the treatment of malaria.[ii]

Ehrlich discovered that when MB was injected into animals in the lab, it would quickly concentrate in the brain. And had an uncanny ability to selectively target diseased tissues in the body.

It was Ehrlich who coined the term “Magic Bullet” for this unique action displayed by Methylene Blue. A term still in use today.

Methylene Blue has since been used to treat dementia, in cancer chemotherapy, malaria, methemoglobinemia, urinary tract infections, cyanide and carbon monoxide poisoning.[iii]

As a nootropic, Methylene Blue is used to enhance mitochondrial function, increase cerebral blood flow, and acts as an antidepressant.

What does Methylene Blue to the brain?

How does Methylene Blue work in the brain?

Methylene Blue boosts brain health and function in several ways. But two in particular stand out.

  1. Methylene Blue improves memory. Unlike other nootropics which often work by increasing neurotransmitter synthesis and neural signaling, MB improves memory by increasing brain cell respiration. Or how the brain cell utilizes oxygen.

Studies show dramatic increases of cellular oxygen consumption and glucose uptake when using Methylene Blue. MB increases CMRO2 (cerebral metabolic rate) through increased activity in the mitochondrial electron transport chain.

Methylene Blue increases activity in the mitochondrial electron transport chain.Methylene Blue functions as an alternative electron carrier in the electron transport chain in mitochondria. It accepts electrons from NADH and transfers them to cytochrome c.[iv]

Cytochrome complex (cytochrome c) is a component of the electron transport chain in mitochondria. Playing a role in apoptosis and as an antioxidant.

Methylene Blue also stimulates glucose metabolism. Taken together, increases in CMRO2 and glucose uptake means that MB elevates oxygen consumption which helps glucose increase ATP production.

Increases in ATP production provides more cellular energy for better overall brain function including cognition, mood and memory.

  1. Methylene Blue is an antioxidant. MB has a unique mechanism of action that is fundamentally different from traditional antioxidants. During cellular respiration, the first free radical formed inside a cell is superoxide (O2).

Methylene Blue binds to superoxide and reduces it to water. It stops the oxidative cascade at its very beginning. Before it gets a chance to do damage.[v]

So think of Methylene Blue as having a unique dual property. First, it increases cellular energy production which normally leads to oxidative stress. And second, it eliminates this oxidative stress. Making it a metabolic enhancer and an antioxidant.

Researchers tested Methylene Blue in animal models of neurological disease. First, researchers used rotenone (a potent pesticide) which causes severe dopamine depletion in the part of the brain associated with Parkinson’s.

Methylene Blue rescued brain cell mitochondria from the damaging effects of this toxin. By donating electrons in the electron transport chain broken by rotenone. Essentially bypassing the broken transport chain with donated electrons as an alternative electron carrier.

Methylene Blue also countered cerebral ischemia reperfusion damage. The tissue damage caused when blood supply returns to tissue after a lack of oxygen from a stroke. And can occur with Traumatic Brain Injury. MB accomplished this by rerouting mitochondrial electron transfer.

And Methylene Blue dramatically countered the behavioral, neurochemical, and neuropathological impairment found in Parkinson’s disease.[vi]

How things go bad

As we live life, our brain chemistry and metabolism changes.

↓ Mitochondrial energy levels decline

↓ Attention, memory and mental agility decline

↓ Tau proteins and amyloid plaques clog the brain

Free radicals damage brain cell mitochondria

Cerebral blood flow declines

All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more.

So Methylene Blue can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting brain cell mitochondria energy production levels. And improving cerebral blood flow.

What to expect when taking Methylene Blue

Methylene Blue benefits

Low dose Methylene Blue supplementation provides memory enhancing effects in animals and humans. It works as an antidepressant, is anti-aging, helps dementia, Huntington’s and Alzheimer’s.

Methylene Blue increases low blood pressure, improves cognition in healthy people, boosts mitochondrial function, is anti-microbial, can help eliminate fear and even slow skin aging.

Methylene Blue boosts acetylcholine

Research shows that Methylene Blue is an acetylcholinesterase inhibitor with a preference for muscarinic acetylcholine receptors. Meaning MB prevents the breakdown of acetylcholine and making more available in your brain.[vii]

Methylene Blue is an antidepressant

Methylene Blue is a monoamine oxidase inhibitor (MAOI). It inhibits MAO-A more than MAO-B, but inhibits both at large doses.[viii]

One study in 1987 showed that 15 mg per day of Methylene Blue was a potent antidepressant in those with severe depression.[ix]

Another study with 31 Bipolar Disorder patients compared 300 mg per day of Methylene Blue with 15 mg per day. The patients were also on lithium treatment. The study showed that the 300 mg dose of Methylene Blue was a “useful addition to lithium in the long-term treatment of manic-depressive psychosis”. And patients were significantly less depressed.[x]

Methylene Blue resists Alzheimer’s Disease

Alzheimer’s disease and other forms of dementia are associated with a buildup of the protein Tau. Clinical trials show that Methylene Blue inhibits Tau formation. And is under consideration as a treatment for Alzheimer’s.[xi]

Methylene Blue has an inhibitory action on the cGMP pathway, and affects other molecular events closely related to the progression of Alzheimer’s.

Methylene Blue boosts neuron resistance to the formation of amyloid plaques and neurofibrillary tangles. And helps repair impairments in mitochondrial function and cellular metabolism.

Research also shows that cholinergic, serotonergic and glutamatergic systems all play important roles in the development of Alzheimer’s and other cognitive disorders. Methylene Blue provides beneficial effects in mediating these pathways.[xii]

This is particularly significant because most existing treatments for Alzheimer’s can only prevent the disease before it is diagnosed. But Methylene Blue shows promise in delaying the effects of Alzheimer’s and dementia after it is diagnosed.

Methylene Blue is anti-aging

Does methylene blue increase dopamine?Research shows that Methylene Blue is an effective anti-aging nootropic. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37-70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium.

Methylene Blue is considered a redox agent. Meaning it cycles between oxidized and reduced forms. This cycling by MB helps block oxidant production in brain cell mitochondria.[xiii]

Mitochondrial complex IV is the last enzyme in the respiratory electron transport chain in mitochondria. The last step in synthesizing ATP. Your cellular source of energy.

Iron (heme) is an essential element and participates in oxygen transport, DNA synthesis and electron transport. Heme synthesis begins in mitochondria. Every cell requires heme to function properly.[xiv]

Senescence or biological aging is the gradual deterioration of cellular function. And is caused by telomere shortening that triggers DNA damage in response to reactive oxygen species, hydrogen peroxide (H2O2), cadmium and other toxins. Methylene Blue helps prevent premature senescence or premature cell death.

Methylene Blue improves memory

Animal studies have shown that a single low dose of Methylene Blue enhances long-term contextual memory. This type of memory is the conscious recall of the source and circumstances of a specific memory.

Other studies show that Methylene Blue in low doses taken after the event helps memory retention of the event. A study done with rats revealed why this works.

In this study, rats received 1 mg/kg of MB post-training for 3 days. The researchers then measured cytochrome c oxidation in participants brains. The idea was to determine if an increase in metabolic energy was behind the memory enhancing qualities of MB.

The study found that in the Methylene Blue treated group, brain cytochrome oxidase activity was 70% higher than in the placebo-treated group.

The findings suggest that repeated post-training supplementation of Methylene Blue improves memory consolidation. And this memory boost is due to the increased metabolic capacity in brain regions that require more energy during discrimination learning.[xv]

 How does Methylene Blue feel?

Is Methylene Blue safe to ingest?Many who use Methylene Blue say if you try this nootropic that you will likely feel different than any other supplement you’ve ever tried.

Neurohackers report when reading or studying, once you’re done, you should feel like you fully understand the subject material. And you’ll be able to use what you learned in the future.

Methylene Blue seems to facilitate a full understanding of something on the first try.

Many neurohackers report the biggest nootropic effect they experience with Methylene Blue is “after the fact learning”. You take in the information. And it’s like your brain sorts through the material. Then stores it in a form you can easily access later.

Methylene Blue has this uncanny ability to rewire your brain to forget about any negative associations you have of a situation. And only retains the positive aspects of that memory.

Some report that Methylene Blue makes you “feel young again”. It eliminates social anxiety. You’ll feel focused and more confident.

Some say that workouts seem easier because you have more energy. Your mitochondria are energized. And you may find that recovery from workouts is easier.

Some users love its anxiolytic benefits because Methylene Blue helps eliminate stress. So you have more energy in any situation with a relaxed state of mind.

And one recurring theme from many is improved sleep while using Methylene Blue.

Studies show Methylene Blue can prevent or slow the decline of mitochondrial function.

Methylene Blue Clinical Research

Research into Methylene Blue for its therapeutic value goes back to the late 1800’s. But it’s only in the last couple of decades that scientists have been able to decode exactly how Methylene Blue works in the brain. All the way down to the molecular level in mitochondria.

A study in 2017 found that Alzheimer’s Disease could be caused by more than the accumulation of amyloid beta in the brain. The scientists looked into the two main components that produce energy in cells.

  1. Glycolysis is the mechanism used to convert glucose into fuel within mitochondria.
  2. Creating this fuel in mitochondria uses oxygen in a process called mitochondrial respiration.

The researchers found that as the brain ages, mitochondrial metabolism deteriorates. Resulting in a reduction in the molecules needed for energy production. And possibly the main culprit behind many neurological diseases including Alzheimer’s and Parkinson’s.[xvi]

A study conducted at Children’s Hospital Oakland Research Institute may have found the solution to this mitochondrial energy problem in brain cells.

The researchers found that Methylene Blue can prevent or slow the decline of mitochondrial function.

One of the key aspects of Alzheimer’s is mitochondrial dysfunction. Specifically complex IV dysfunction. And this is where Methylene Blue steps in.

The study found that Methylene Blue enhances complex IV in mitochondria. It increases oxygen consumption. And it reverses premature cell death.

The researchers concluded that Methylene Blue may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer’s disease.[xvii]

Methylene Blue Improves Memory

26 healthy volunteers aged 22 – 62 participated in a double-blind, randomized, placebo-controlled clinical trial. Purpose of the study was to measure the effects of Methylene Blue on working memory and sustained attention.

Study results showed that a single low-dose of Methylene Blue resulted in an increase in short-term memory ability. In an area of the brain associated with the senses and visual processing.

Timothy Duong, Ph.D., the study author concluded Methylene Blue showed promise “in healthy aging, cognitive impairment, dementia and other conditions that might benefit from drug-induced memory enhancement”.[xviii]

Another study published in the American Journal of Psychiatry tested fear extinction (elimination of fear) and contextual memory. Both are forms of long-term memory.

In this study, participants received either Methylene Blue or a placebo after being placed in a small dark chamber for a couple of minutes to address their fear.

One month later, participants that had used Methylene Blue had less retained fear than those given a placebo. The study authors concluded, “Methylene Blue enhances memory and the retention of fear extinction”.[xix]

Methylene Blue helps Bipolar Disorder

Animal studies have demonstrated that Methylene Blue can provide antidepressant and anxiolytic benefits. Possibly because it can increase serotonin and dopamine levels.

Canadian researchers noted that Methylene Blue also improved mitochondrial function and decreased oxidative damage. So, they hypothesized that Methylene Blue may be effective for bipolar disorder symptoms if combined with lamotrigine which is used as a mood stabilizer.

This study at Dalhousie University in Halifax compared the effectiveness of lamotrigine (Lamictal®) along with daily supplementation of either 195 mg or 15 mg of Methylene Blue in patients with Bipolar Disorder.

Patients took a dose (Lamictal and either 195 mg or 15 mg of Methylene Blue) for three months. Then proceeded to reduce Methylene Blue dosage for an extended period of 3 months. The team found that bipolar participants had reduced depression and anxiety when taking the higher dose of Methylene Blue compared to when they were on the lower dose.

Several Bipolar Disorder patients in the study chose to continue using Methylene Blue after the study concluded.[xx]

Methylene Blue Dosage Recommendations

Recommended safe doses based on clinical studies with animals and humans ranges from 0.5 – 4 mg/kg. So a 90 kg (200 lb.) body weight translates to 45 – 360 mg of Methylene Blue.

How much oral methylene blue should I take?45 mg of a Methylene Blue dose is a safe. But 360 mg of MB is much too high in my opinion even if you’re 200 lbs.

The bottom line is there is no true recommended dose for Methylene Blue. My recommendation is start with the lowest dose of 0.5 mg/kg and see how you react. A repeat dose may be taken if no effects occur.

Methylene Blue is water-soluble so you don’t need to take it with a meal, or healthy fat like some nootropics.

Methylene Blue has a half-life of about 5 hours. So you can dose twice a day.

Methylene Blue is famous for turning urine blue. But for most neurohackers, your urine will only stain blue at doses roughly exceeding 500 mcg. Some recommend preventing blue urine by mixing Methylene Blue with ascorbic acid for 3 hours before taking it.

Methylene Blue is also available as a doctor-administered injection for therapeutic use. IV Methylene Blue is typically used to treat diseases like malaria or with anti-cancer therapy.

Methylene Blue Potential Drug Interactions & Side Effects

Methylene Blue shows a hermetic dose-response, with opposite effects at low and high doses.

In other words, lower doses of Methylene Blue work well as a nootropic. But high doses do not because MB can potentially “steal” electrons away from the electron transport chain. Disrupting the redox balance and acting as a pro-oxidant (instead of an antioxidant).[xxi]

Methylene Blue Potential Drug Interactions & Side EffectsAdverse effects of Methylene Blue also come from chemical impurity. Even pharmaceutical (USP) grade Methylene Blue can contain impurities like arsenic, aluminum, cadmium, mercury and lead which puts you at increased risk for heavy metal toxicity.

At low doses, these contaminants are not that big of a problem. But higher doses will result in the accumulation of these toxins in your cells. Doctors should monitor patients with any hepatic impairment due to toxins related to high doses of serotonergic drugs like Methylene Blue.

Side effects with Methylene Blue are rare when doses are under 2 mg/kg. But can include stomach pain, chest pain, dizziness, headache, sweating, confusion, high blood pressure, shortness of breath, accelerated heartbeat, tremor, skin turning blue, urine turning blue or green, reduction of red blood cells, or jaundice (only reported in infants).

Reduce the Risk of Serotonin Syndrome

Monoamine Oxidase (MAOI) inhibition becomes a big problem at around 2 mg/kg of Methylene Blue. So if you are using antidepressants or antianxiety medications that affect dopamine or serotonin, you should NOT use Methylene Blue.

Because using Methylene Blue with one of these medications could cause possible interactions resulting in a hypertensive crisis or Serotonin Syndrome. Which can be deadly.

This includes not using Methylene Blue if you are using any selective serotonin reuptake inhibitors (SSRI’s) and monoamine oxidase inhibitors (MAOI’s) including 5-HTP, bupropion, buspirone, citalopram, clomipramine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, MAOIs like Marplan, Nardil, and Parnate, milnacipran, mirtazapine, paroxetine, rasagiline, sertraline, selegiline, St. John’s wort, trazodone, tryptophan, Zimelidine, and venlafaxine.

The above list is my no means complete nor does it include all of the drugs that may be contraindicated with Methylene Blue. Check with your health care provider if a drug or supplement you are using may also be contraindicated with this nootropic.

Do not use Methylene Blue if you are pregnant or breast-feeding. Or if you are dealing with any type of renal impairment.

Where to buy Methylene Blue

Methylene Blue is sold as a liquid, and in crystalline powder form.

Industrial-grade and chemical-grade Methylene Blue is sold as a dye or stain. And can consist of more than 8% – 11% of various contaminants. And should NOT be used as a nootropic.

Only pharmaceutical (USP) grade Methylene Blue should be used as a nootropic. Ask for a Certificate of Analysis which should include the amount of contaminants such as arsenic, aluminum, cadmium, mercury and lead.

I recommend CZTL Methylene Blue due to their robust testing program. They ship in 1 gram containers of powder with dosage and mixing instructions in each shipment. Along with a Certificate of Analysis (CofA) verifying the purity of the Methylene Blue you get from them.

Another option in liquid form is Science.bio – Methylene Blue which is pre-mixed. And use the coupon code: davidtomen10 for a 10% discount when you check out.

Nootropics Expert Recommendation

Nootropics Expert Tested and ApprovedMethylene Blue 0.5 – 4 mg/kg of body weight per day

I recommend using Methylene Blue as a nootropic supplement.

Your body does not make Methylene Blue on its own. So to get its benefits you must take it as a supplement.

Methylene Blue is especially helpful for those dealing with anxiety and depression.

Methylene Blue is also particularly useful to students and executives who want to boost cognition, learning and memory.

Methylene Blue is a fast-acting nootropic that can also help prevent brain mitochondrial degeneration. Providing potential as an anti-aging nootropic.

Methylene Blue donates electrons in the electron transport chain in your mitochondria. So experienced neurohackers suggest avoiding CoQ-10 or idebenone when using MB because it seems to make Methylene Blue much less effective. Remember earlier in this review when I said the too much Methylene Blue can be counter-productive. The same applies here.

Idebenone is an Alzheimer’s drug that has some nootropic benefit. But it works similar to Methylene Blue because it acts as a transporter in the electron transport chain in mitochondria. Possibly potentiating Methylene Blue.

I recommend CZTL Methylene Blue

Or Science.bio – Methylene Blue which is pre-mixed. And use the coupon code: davidtomen10 for a 10% discount when you check out.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] Allexsaht W.J. “The use of methylene blue in the treatment of catatonic dementia praecox patients.” Psychiatric Quarterly. 1938;12:245–252.

[ii] Schirmer R.H., Coulibaly B., Stich A., Scheiwein M., Merkle H., Eubel J., Becker K., Becher H., Müller O., Zich T., Schiek W., Kouyaté B. “Methylene blue as an antimalarial agent.” Redox Report. 2003;8(5):272-5. (source)

[iii] Wainwright M., Crossley K.B. “Methylene Blue–a therapeutic dye for all seasons?” Journal of Chemotherapy 2002 Oct;14(5):431-43. (source)

[iv] Wen Y., Li W., Poteet E.C., Xie L., Tan C., Yan L.J., Ju X., Liu R., Qian H., Marvin M.A., Goldberg M.S., She H., Mao Z., Simpkins J.W., Yang S.H. “Alternative mitochondrial electron transfer as a novel strategy for neuroprotection.” Journal of Biological Chemistry. 2011 May 6; 286(18):16504-15. (source)

[v] Poteet E. et. Al. “Neuroprotective Actions of Methylene Blue and Its Derivatives” PLOS One 2012; 7(10): e48279. (source)

[vi] Wen Y., Li W., Poteet E.C., Xie L., Tan C., Yan L.J., Ju X., Liu R., Qian H., Marvin M.A., Goldberg M.S., She H., Mao Z., Simpkins J.W., Yang S.H. “Alternative mitochondrial electron transfer as a novel strategy for neuroprotection.” Journal of Biological Chemistry. 2011 May 6; 286(18):16504-15. (source)

[vii] Pfaffendorf M., Bruning T.A., Batnik H.D., van Zwieten P.A. “The interaction between methylene blue and the cholinergic system.” British Journal of Pharmacology. 1997 Sep;122(1):95-8. (source)

[viii] Ramsay R.R., Dunford C., Gillman P.K. “Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction.” British Journal of Pharmacology. 2007 Nov;152(6):946-51 (source)

[ix] Naylor G.J., Smith A.H., Connelly P. “A controlled trial of methylene blue in severe depressive illness.” Biological Psychiatry. 1987 May;22(5):657-9. (source)

[x] Naylor G.J., Martin B., Hopwood S.E., Watson Y. “A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis.” Biological Psychiatry. 1986 Aug;21(10):915-20. (source)

[xi] Crowe A., James M.J., Lee V.M., Smith A.B. 3rd, Trojanowski J.Q., Ballatore C., Brunden K.R. “Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation.” Journal of Biological Chemistry. 2013 Apr 19;288(16):11024-37 (source)

[xii] Oz M., Lorke D.E., Petroianu G.A. “Methylene blue and Alzheimer’s disease.” Biochemical Pharmacology. 2009 Oct 15;78(8):927-32. (source)

[xiii] Atamna H., Nguyen A., Schultz C., Boyle K., Newberry J., Kato H., Ames B.N. “Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.” FASEB Journal. 2008 Mar;22(3):703-12. (source)

[xiv] Abbaspour N., Hurrell R., Kelishadi R. “Review on iron and its importance for human health” Journal of Research in Medical Sciences 2014 Feb; 19(2): 164–174. (source)

[xv] Wrubel K.M. et. El. “The Brain Metabolic Enhancer Methylene Blue Improves Discrimination Learning in Rats” Pharmacological and Biochemical Behavior. 2007 Apr; 86(4): 712–717. (source)

[xvi] Sonntag K.C., Ryu W., Amirault K.M., Healy R.A., Siegel A.J., McPhie D.L., Forester B., Cohen B.M. “Late-onset Alzheimer’s disease is associated with inherent changes in bioenergetics profiles” Scientific Reports 2017; 7 (source)

[xvii] Atamna H., Nguyen A., Schultz C., Boyle K., Newberry J., Kato H., Ames B.N. “Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.” FASEB Journal. 2008 Mar;22(3):703-12 (source)

[xviii] Rodriguez P., Zhou W., Barrett D.W., Altmeyer W., Gutierrez J.E., Li J., Lancaster J.L., Gonzalez-Lima F., Duong T.Q. “Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.” Radiology. 2016 Nov;281(2):516-526. (source)

[xix] Telch M.J., BRuchey A.K., Rosenfield D., Cobb A.R., Smits J., Pahl S., Gonzalez-Lima F. “Effects of Post-Session Administration of Methylene Blue on Fear Extinction and Contextual Memory in Adults With Claustrophobia” American Journal of Psychiatry Volume 171, Issue 10, October 2014, pp. 1091-1098 (source)

[xx] Alda M., McKinnon M., Blagdon R., Garnham J., MacLellan S., O’Donovan C., Hajek T., Nair C., Dursun S., MacQueen G. “Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study.” British Journal of Psychiatry. 2017 Jan;210(1):54-60 (source)

[xxi] Rojas J.C., Bruchey A.K., Gonzalez-Lima F. “Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue” Progress in Neurobiology. 2012 Jan; 96(1): 32–45. (source)

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Join The Discussion - 749 comments

Anette Mnabhi
September 24, 2020

Methylene Blue is available from compounding pharmacies, there are several that make it. Some in capsule form, nasal spray, Liposomal form, and in varying doses. Interesting information in general.

Nicole
August 29, 2020

Hi David,
Do you have any insight as to why MB USP grade from pharmacy caused the opposite effects of what science and biohackers claim positively? For example, when I take it (started 12.5 then up to 25mg, weigh 47kg), I get very depressed, severely brain fogged/dead- can’t comprehend anything and severe insomnia despite my sleep cocktail I depend on to sleep that normally works. This went on for two months until I stopped and recovered.

I’m considering taking it despite the brain hell due to GI/bowel improvements I experienced and I just got a bad infection nothing (and I mean nothing) will touch. Originally prescribed for lyme coinfection as part of larger protocol but since it went so bad, we cancelled it.

Any ideas biochemically why I was an insomniac, brain dead and depressed, it was severe too, not just minor stuff I deal with daily.

Thanks! 😉

    David Tomen
    August 31, 2020

    Nicole, Methylene Blue acts as an MAOI which boosts dopamine. norepinephrine and possibly serotonin. And as an acetylcholinesterase inhibitor which boosts acetylcholine. If you are using any drug that affects any of these neurotransmitters you’ll have problems using MB. Of if you are using any supplement to boost any of these neurotransmitters same thing (i.e. “my sleep cocktail I depend on to sleep”).

    Please scroll back up and read the “Side Effects” section of this review as well. It’ll provide more detail on what else could go wrong.

      Nicole
      September 1, 2020

      Thanks for the reply. I did ask because what I read in your article didn’t reflect as an issue with methylene blue.

      On a minor level melatonin, THC/CBD of course have some neurotransmitter effects but it’s pretty diluted across the board in the grand scheme and nothing like SSRI’s etc -none of which I take.
      I certainly wouldn’t have thought Melatonin and CBD/THC would be enough because I was considered (assumed) low in everything to start. Perhaps I don’t clear certain neurotransmitters away quick enough (dopamine etc), although I thought genetically I was a “dopamine chaser”. I may need to resort to my genetic information… bit of a confusing wormhole. While it always seems like I need more serotonin symptomatically, people like Ray Peat would say otherwise. Years ago a ND had me on tryptophan with a similar but slightly different response (just insomnia/anxiety, heart palps, nausea, not brain dead).
      I think one has to really know biochemistry and uniquely to themselves beyond the obvious. I’m just too sick to sort it out ad too broke to hire someone to attempt it 🙁

      Thanks for what you shared though!!

      If anyone else has hacked this issue I welcome guidance! It may help fight some infections 😉

        Jenn
        December 3, 2021

        Hi Nicole, for what it’s worth my experience with medical cannabis was that the THC thoroughly messed up my hormonal axis worsened my anxiety and caused lots of issues. It also severely affected my cognitive abilities which is why I’ve been looking into nootropics to help me overcome that damage. In my honest opinion there isn’t enough research on how THC negatively affects us. Here’s an article that helped me https://www.zrtlab.com/blog/archive/the-effects-of-cannabis-on-your-hormones/ and if you decide to quit THC there will be some headaches and such but just determine to get through the first week and things will get better from there.

Jonathan
August 18, 2020

Hi David,

Everything I’m reading here makes Methylene blue sound incredible, truely a magic bullet! Given this though, I’m curious as to why someone so educated as yourself seems to have stopped taking it.

I’m assuming you no longer take it since it is not on your “What I take” page. If I am correct in this assumption, please could you give an explanation of why you no longer feel the need?

Given its miriade benefits, I feel it would be very useful for those of us considering it to understand the trade offs garnered from your experience, for this versus other nootropics, and what ultimately led to the decision.

Many thanks for your time.

    David Tomen
    August 19, 2020

    Jonathan, the company that I was getting Methylene Blue stopped selling it. Or went out of business. Can’t remember which. I couldn’t find another reliable source of Methylene Blue. And haven’t tried very hard since to find another source. But I loved the effect and should track down another supplier. Just ‘haven’t got around to it’.

      Jonathan
      August 21, 2020

      Thanks for you reply David. From what I’ve seen of the comments below, you appear to refer a number of people to sigma labs. If it’s not impertinent, is there a reason you don’t use this yourself yet, and if you did start using it, would you still stack it with the majority of other substances in your current stack?

      All the best!

        David Tomen
        August 22, 2020

        Jonathan, no real reason I no longer use MB. I’m already using so many nootropics that adding another likely wouldn’t help me much. But if I did start using it again I would have no problem just adding it to my current stack.

        And I’ve referring people to Sigma because they’re the only show on the planet that can make a pharmaceutical grade MB that I know of.

        Vendors that carry it are here today and gone tomorrow. And I gave up trying to keep up with who carries it now. I think someone put a link to a current supplier here in the comments section of this thread. If I remembered correctly, I have not dealt with that company. And cannot say whether they have a quality product or not. And no one has reported back on them either.

Jeru
August 16, 2020

Hi David

Are these dosage values in liquid concentrate solution (ml) form to be taken diluted with water, if so what strength should the initial solution be 1-3%?

Or are the measurements in raw powder mg form to be taken via capsule?

Thanks

Jeru

    David Tomen
    August 16, 2020

    Jeru, pharmaceutical (USP) grade Methylene Blue comes in a consistent concentration as a liquid which is what my dosage recommendations are based on. You need to get how much MB is in each drop from the manufacturer. Then measure your dose from there. It doesn’t matter that the concentration of MB is in water. It’s how much MB is actually in the glass.

    I’m not aware of anyone encapsulating MB powder and using it as a nootropic. That would be a whole other dosage calculation and I’m not so sure it would be safe. Liquid is best as a nootropic. Even if you dissolve the powder in water. Then you’d need to know how concentrated the powder was and calculate what your concentration was for dosage.

Alex
August 5, 2020

Hi David. I am an MD practicing functional medicine. I have a handful of patients with neurodegenerative disorders that i want to treat with MB. I am researching an IV protocol for administration of MB. I know I want to be at the lowest dose possible but i am targeting 1.5-2 mg / kg for hopefully a more therapeutic response. If you have any opinions or recommendations in terms of which product and any regimen recommendation id be most appreciative. If you prefer to email me direct my address is [email protected]

    David Tomen
    August 6, 2020

    Alex, see if you can get a pharmaceutical grade MB from these guys: https://www.sigmaaldrich.com/

      Bill Hunsinger
      September 30, 2020

      I have gone to this site and have no idea which of their products would be ok. They seem to be geared to sell them them Research Labs for Lab use.

        David Tomen
        October 1, 2020

        Bill, your are correct because that is their main business model. I’ve been told by a couple of people that they refuse to sell to individuals. And yet others do buy from them.

        But it takes some digging because you are looking for pharmaceutical grade MB. And it will state that somewhere in the description.

newton
July 27, 2020

Hello David Tomen, I’m new to nootropics, I have a doubt I can take MB on alternate days with ritalin because of the risk of Serotonin Syndrome?

    David Tomen
    July 27, 2020

    Newton, I’ve used Methylene Blue while on Ritalin without any problems. But it is something to be aware of and keep an eye on. Start with the lowest effective dose of MB and see how you feel. Get familiar with the early symptoms of Serotonin Syndrome so you know what to watch out for.

      Newton
      July 29, 2020

      Thank you very much David, I will follow your advice and follow the symptoms.

Sam
July 20, 2020

Hi,

I am new to the world Nootropics , i just bought your book today

i was researching Methylene Blue and noticed you haven’t mentioned Methylene Blue in your book , any specific reason ?

i want to start using it not just as a nootropic , but i also read that it may help with the severity of infection in COVID 19 management

    David Tomen
    July 20, 2020

    Sam, I did my research on Methylene Blue after Head First was published. But it will certainly be in my 2nd Edition.

      Sam
      July 20, 2020

      Thankyou for your reply David , when will the second edition be out ?

        David Tomen
        July 20, 2020

        Sam, I’m hoping before the end of the year.

        Sam Enig
        August 8, 2020

        I should have waited till then to buy your book ,
        will there be any special disocunt for those who have already bought your book ?

        David Tomen
        August 9, 2020

        Sam, I highly doubt it. And it’s because of the amount of time and work that goes into writing a book like Head First. The other thing is how much value is in a book like Head First. Even at its current price it’s about half the cost of a high quality pre-made nootropic stack which lasts a month. And Head First provides value for as long as it’s available to reference.

Dor Konforty
June 29, 2020

What do you think is the MB dose that would make adding CoQ10 unskillful?

    David Tomen
    June 30, 2020

    Dor, I haven’t seen any data or clinical studies showing a contraindication between MB and CoQ10. Both influence mitochondria and the electron transport chain.

    So it’s possible that CoQ10 would amplify the effects of MB. In fact, there are clinical studies in animals where Methylene Blue works with CoQ10 which you can easily find with an online search. But no indication on how this would work in humans that I’m aware of.

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