Can Methylene Blue Be a Nootropic?

Methylene blue (MB), also known as methylthioninium chloride, is a salt used as a medication and dye. Sometimes used for used to methemoglobinemia (a blood disorder). Though, recently it has begun to gain recognition for potential cognitive-enhancing and mitochondrial energizing benefits.^[1,2]

Research suggests that it may improve mitochondrial function and decrease the production of proteins that may cause Alzheimer's disease. Other properties of methylene blue have led to further research and intrigue in this particular substance.

A Quick Look at Methylene Blue

Methylene blue was discovered in the late 1800s. It was originally used as a dye for textiles. However, it quickly became noted for its medicinal properties.

Methylene blue’s amazing ability to treat malaria was discovered by Nobel prize-winning physician Paul Ehrlich. Other discovered properties of MB included antifungal, antibacterial, and antiviral. It has also proved useful as an indicator dye in MRI scans, surgical marking, and other medical staining purposes.^[3,4]

More recently, methylene blue’s monoamine oxidase inhibiting and nitric oxide enzyme regulating mechanisms of action were discovered to have antidepressant-like and antipsychotic properties. One study even suggests MB’s potential neuroprotective properties and displayed ability to improve learning and memory recall.^[5,6]

Pubmed published August 2021 Methylene Blue may be effective in increasing blood oxygen and reducing respiratory distress in COVID-19 patients.

Methylene Blue Mechanisms of Action

Mitochondria need oxygen to make ATP. MB has an ability to act like oxygen, increasing oxygen consumption and ATP production in areas such as nerve cells in the brain — resulting in memory improvement.^[7,8]

MB increases glucose metabolism in cases without oxygen and boosts the amount of NAD+ generated by mitochondria. The more NAD+, the younger your cells are as a result of sirtuin activation.^[9]

Low doses of MB alter the heme (iron) of hemoglobin allowing more oxygen in red blood cells, improving hemoglobin's oxygen-transporting capacity, and resulting in increased ATP production from the electron transport chain.^[10]

MB also effectively binds to free oxide radicals, preventing oxidative damage from stress before it begins.

MB acts as a monoamine oxidase inhibitor (MAOI), preventing the breakdown of monoamines and leading to an increase in dopamine, melatonin, and serotonin in the brain.^[11]

Low-dose MB also acts as a cholinesterase inhibitor, increasing acetylcholine and hence promoting arousal, attention, memory, and motivation.^[12,9]

Methylene Blue Use Cases

Methylene blue’s ability to absorb into tissues concentrated with mitochondria and cross the blood-brain barrier, and also enter the heart, liver, and kidneys, has led to a number of interesting potential applications.^[13]

The only FDA-approved use case for methylene blue is methemoglobinemia — where it helps hemoglobin accept oxygen. In certain circumstances, it may also be used for carbon monoxide poisoning.

Methylene Blue may improve memory by increasing brain cell respiration. MB increases cerebral metabolic rate by helping cells absorb more glucose and oxygen due to increased activity in the mitochondrial electron transport chain.^[14]

The increase in oxygen and glucose allows for increased ATP production and hence improved brain function including regions of the brain that are associated with mood, memory and cognition.^[15]

One study that MB shows promise in conditions that may benefit from preventing cognitive decline, such as dementia and aging.

Methylene Blue counters cerebral ischemia-reperfusion damage — the tissue damage caused by a lack of oxygen typically from a stroke or TBI — by rerouting mitochondrial electron transfer.^[16]

Safety

MB, when taken in appropriate amounts and purity/potency tested, is a very safe drug. The most frequent (and non-significant) MB side effect is blue urine.

Due to the danger of serotonin syndrome and hypertensive crisis, DO NOT combine any amount of MB with SSRIs, SNRIs or other drugs that increase serotonin production. Note: Many other illicit drugs, such as MDMA and psilocybin, also increase serotonin.

Pregnant women and breastfeeding mothers should not use Methylene Blue.

DO NOT consume fish tank cleaners that contain MB. They also contain poisonous chemicals like arsenic, cadmium, and lead. Any MB consumed by humans must be pharmaceutical grade and completely free of impurities — such as found in our Nootropic Tincture.

Final Thoughts

At Clean Remedies, we source all our materials the best way we know how. All our hemp products are organically sourced, and our Methylene Blue Nootropic Tincture is made with pharmaceutical-grade ingredients.

Sources

1. Rojas, J. C., Bruchey, A. K., & Gonzalez-Lima, F. (2012). Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Progress in neurobiology, 96(1), 32–45. https://doi.org/10.1016/j.pneurobio.2011.10.007
2. Tucker D, Lu Y, Zhang Q. From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue. Mol Neurobiol. 2018 Jun;55(6):5137-5153. doi: 10.1007/s12035-017-0712-2. Epub 2017 Aug 24. PMID: 28840449; PMCID: PMC5826781.
3. BASF. (n.d.). Pioneering thinker then and now: Methylene blue. Retrieved September 13, 2021, from https://www.basf.com/global/en/media/magazine/archive/issue-4/pioneer-thinker-then-and-now-methlyene-blue.html
4. IBM Watson Health. (2021, September 01). Hyoscyamine, Methenamine, Methylene Blue, Phenyl Salicylate, And Sodium Phosphate (Oral Route) Description and Brand Names. Retrieved September 13, 2021, from https://www.mayoclinic.org/drugs-supplements/hyoscyamine-methenamine-methylene-blue-phenyl-salicylate-and-sodium-phosphate-oral-route/description/drg-20075036
5. Harvey BH, Duvenhage I, Viljoen F, Scheepers N, Malan SF, Wegener G, Brink CB, Petzer JP. Role of monoamine oxidase, nitric oxide synthase and regional brain monoamines in the antidepressant-like effects of methylene blue and selected structural analogues. Biochem Pharmacol. 2010 Nov 15;80(10):1580-91. doi: 10.1016/j.bcp.2010.07.037. Epub 2010 Aug 10. PMID: 20699087.
6. Rojas, J. C., Bruchey, A. K., & Gonzalez-Lima, F. (2012). Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Progress in neurobiology, 96(1), 32–45. https://doi.org/10.1016/j.pneurobio.2011.10.007
7. Callaway NL, Riha PD, Bruchey AK, Munshi Z, Gonzalez-Lima F. Methylene blue improves brain oxidative metabolism and memory retention in rats. Pharmacol Biochem Behav. 2004 Jan;77(1):175-81. doi: 10.1016/j.pbb.2003.10.007. PMID: 14724055.
8. Gonzalez-Lima, F., & Bruchey, A. K. (2004). Extinction memory improvement by the metabolic enhancer methylene blue. Learning & memory (Cold Spring Harbor, N.Y.), 11(5), 633–640. https://doi.org/10.1101/lm.82404
9. Gabrielli D, Belisle E, Severino D, Kowaltowski AJ, Baptista MS. Binding, aggregation and photochemical properties of methylene blue in mitochondrial suspensions. Photochem Photobiol. 2004 Mar;79(3):227-32. doi: 10.1562/be-03-27.1. PMID: 15115294.
10. Smith RP, Thron CD. Hemoglobin, methylene blue and oxygen interactions in human red cells. J Pharmacol Exp Ther. 1972 Dec;183(3):549-58. PMID: 4636392.
11. Gillman PK. Methylene blue is a potent monoamine oxidase inhibitor. Can J Anaesth. 2008 May;55(5):311-2; author reply 312. doi: 10.1007/BF03017212. PMID: 18451123.
12. Pfaffendorf M, Bruning TA, Batnik HD, van Zwieten PA. The interaction between methylene blue and the cholinergic system. Br J Pharmacol. 1997 Sep;122(1):95-8. doi: 10.1038/sj.bjp.0701355. PMID: 9298533; PMCID: PMC1564911.
13. Giocomo, L.M., Hasselmo, M.E. Neuromodulation by Glutamate and Acetylcholine can Change Circuit Dynamics by Regulating the Relative Influence of Afferent Input and Excitatory Feedback. Mol Neurobiol 36, 184–200 (2007). https://doi.org/10.1007/s12035-007-0032-z
14. Wen Y, Li W, Poteet EC, Xie L, Tan C, Yan LJ, Ju X, Liu R, Qian H, Marvin MA, Goldberg MS, She H, Mao Z, Simpkins JW, Yang SH. Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem. 2011 May 6;286(18):16504-15. doi: 10.1074/jbc.M110.208447. Epub 2011 Mar 18. PMID: 21454572; PMCID: PMC3091255.
15. Poteet, E., Winters, A., Yan, L. J., Shufelt, K., Green, K. N., Simpkins, J. W., Wen, Y., & Yang, S. H. (2012). Neuroprotective actions of methylene blue and its derivatives. PloS one, 7(10), e48279. https://doi.org/10.1371/journal.pone.0048279
16. Rodriguez P, Zhou W, Barrett DW, Altmeyer W, Gutierrez JE, Li J, Lancaster JL, Gonzalez-Lima F, Duong TQ. Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain. Radiology. 2016 Nov;281(2):516-526. doi: 10.1148/radiol.2016152893. Epub 2016 Jun 28. PMID: 27351678; PMCID: PMC5084971.