Methylene Blue

Dosing from the Literature

Published for focus: a single 280 mg dose in one 26-person study. Not published: any trial of the 5–20 mg daily doses biohackers take.

Dosing differs by use: the approved IV dose for methemoglobinemia, off-label hospital doses, one trial dose and a community figure.

What It Is

Methylene blue (methylthioninium chloride, MTC; C₁₆H₁₈ClN₃S; MW 319.85 anhydrous, 373.90 as the trihydrate) is a dark-green crystalline solid that dissolves in water to produce its characteristic intense blue solution. It is a phenothiazine, and it was the lead compound for the antimalarials quinacrine and chloroquine and for the first antipsychotic drugs, such as chlorpromazine (Bruchey & Gonzalez-Lima, 2008). It was first synthesized by Heinrich Caro at BASF in 1876 as a textile dye for cotton and was rapidly repurposed as a biological stain and antimicrobial by Paul Ehrlich in the 1890s, who used it as a malarial therapeutic before chloroquine supplanted it. In this sense, methylene blue is credited as the first fully synthetic drug ever used in medicine.

Its modern approved medical indication is as an antidote for acquired methemoglobinemia — a condition where iron in hemoglobin is oxidized from ferrous (Fe²⁺) to ferric (Fe³⁺), blocking oxygen transport. Intravenous methylene blue at 1–2 mg/kg is reduced by NADPH-methemoglobin reductase to leuco-methylene blue, which in turn reduces methemoglobin back to functional hemoglobin. The FDA-approved branded product is ProvayBlue (Provepharm, NDA 204630, approved April 2016). Methylene blue is also on the WHO Model List of Essential Medicines and is used off-label for vasoplegic syndrome (cardiopulmonary bypass shock), ifosfamide-induced encephalopathy, and intraoperative localization (parathyroid, lymph node, ureteric fistula).

What has made methylene blue newly visible in the optimization and longevity communities is its ability at low doses to act as an alternative electron carrier in the mitochondrial electron transport chain (ETC). MB cycles between an oxidized form (blue MB⁺) and a reduced form (colorless leucomethylene blue, MBH₂), and in that cycle can accept electrons from NADH and donate them directly to cytochrome c — effectively creating a bypass around Complex I and Complex III, the two principal sites of physiological electron leak and reactive oxygen species (ROS) production. Low-dose MB therefore increases oxidative phosphorylation efficiency and simultaneously reduces ROS generation — a rare combination (Atamna 2008).

Methylene blue shows a hormetic dose-response, with opposite effects at low and high doses (Rojas et al., 2012); the 2016 human study's authors place its memory effects at single doses of 0.5–4 mg/kg and opposite effects above 10 mg/kg (Rodriguez et al., 2016). Large IV doses (cumulative 7 mg/kg or more) can themselves cause mild methemoglobinemia, and the label's G6PD contraindication and serotonin-syndrome boxed warning apply at its approved 1 mg/kg dose (ProvayBlue label, 2025).

A parallel line of development explored methylene blue derivatives in Alzheimer's disease. TauRx Therapeutics' LMTM (TRx0237, leuco-methylthioninium bis(hydromethanesulfonate)) is a stabilized reduced form of methylene blue designed to inhibit tau protein aggregation — the pathological hallmark of Alzheimer's. LMTM failed its primary endpoints in two Phase III trials (TRx-005, TRx-015) but showed possible monotherapy signal, and TauRx's LUCIDITY confirmatory Phase III trial was completed in April 2023 (ClinicalTrials.gov NCT03446001). The LMTM program is mechanistically connected to MB but uses a different pharmaceutical salt and dosing regimen.

Mechanism of Action

Methylene blue has multiple cellular and molecular targets (Oz et al., 2011), and its dose-response is hormetic, with opposite effects at low and high doses (Rojas et al., 2012).

• Alternative mitochondrial electron carrier — Flavin enzymes use NAD(P)H to reduce MB to colorless leucomethylene blue (MBH₂), and cytochrome c re-oxidizes it; a 2008 study proposed this mitochondrial cycling as the reason MB delayed senescence in human fibroblasts (Atamna et al., FASEB 2008). Reviews describe reduced MB donating electrons to coenzyme Q and possibly cytochrome c, raising cytochrome oxidase (complex IV) activity and oxygen consumption, bypassing blocked points in the chain, and, at low concentrations, passing electrons to oxygen in a way that would cut superoxide (Rojas et al., Prog Neurobiol 2012). This is the central mechanistic claim for the low-dose nootropic use.
• Hormetic dose-response — Low and high doses have opposite effects. In rats, wheel running peaked at 4 mg/kg and fell below control at 50 mg/kg or more, and in rat brain homogenates cytochrome oxidase activity peaked at 0.5 μM and fell below baseline at 10 μM (Bruchey & Gonzalez-Lima, 2008). In cell cultures, high (micromolar) but not low (nanomolar) concentrations raised oxidant levels, and high IV doses cause methemoglobinemia (Rojas et al., Prog Neurobiol 2012). The 2016 human study's authors put the memory-enhancing range at single doses of 0.5–4 mg/kg and opposite effects above 10 mg/kg (Rodriguez et al., 2016).
• Methemoglobinemia reversal — The label describes NADPH reductase converting methylene blue to leucomethylene blue, which reduces the ferric iron of methemoglobin back to the ferrous iron of normal hemoglobin. In the label's two studies of 31 adults, most given 1 mg/kg, 9 of the 12 checked within 2 hours had at least halved their methemoglobin at 1 hour (ProvayBlue label, 2025). This is the use FDA approved.
• Monoamine oxidase inhibition (MAO-A > MAO-B) — MB selectively inhibits MAO-A, with IC₅₀ values of 27–180 nM in the studies reviewed, and antidepressant effects have been linked to this inhibition (Oz et al., 2011); a review notes it is unclear whether such effects on neurotransmission matter in the body (Rojas et al., Prog Neurobiol 2012). FDA points to MAO-A inhibition as the likely cause of serotonin syndrome when MB is combined with serotonergic drugs (FDA Drug Safety Communication, 2011); the label's boxed warning names SSRIs, SNRIs, MAOIs and opioids, and its interaction list adds bupropion, buspirone, clomipramine, mirtazapine, linezolid and dextromethorphan (ProvayBlue label, 2025).
• Tau aggregation inhibition — In a cell-free assay, MB blocked the tau–tau binding that builds Alzheimer-type filaments, though only at concentrations higher than can be reached clinically (Wischik et al., 1996; PNAS). Its stable reduced form, LMTM, inhibits tau aggregation in vitro and in transgenic mice, and it went into TauRx's Phase III Alzheimer's program (Gauthier et al., 2016).
• Amyloid-β aggregation — In lab studies MB inhibited the formation of amyloid-β oligomers, but reports on fibril formation conflict, with both inhibition and promotion described (Oz et al., 2011). LMTM missed its Phase III primary endpoints (Gauthier et al., 2016).
• Nitric oxide synthase (NOS) inhibition — MB directly inhibits both the constitutive and inducible forms of NOS, and at 1–10 μM it is used in the lab to inhibit soluble guanylate cyclase (Oz et al., 2011). NOS inhibition mediates its cardiovascular effects, the basis of its use in septic shock (Rojas et al., Prog Neurobiol 2012), and nitric oxide's role in vasoplegia after cardiac surgery was the rationale for the vasoplegia trial (Levin et al., 2004).
• Antimicrobial activity — MB has been used as an antiseptic and as a photosensitizer, and light activation significantly increases its antifungal and antibacterial activity (Oz et al., 2011). It selectively inhibits the glutathione reductase of the malaria parasite Plasmodium falciparum; in an uncontrolled study in 435 young children in Burkina Faso, MB appeared to have efficacy, but MB with chloroquine was clearly not effective against malaria (Meissner et al., 2006).
• Memory and attention imaging — Rodriguez et al. (Radiology 2016; PMID 27351678) gave 13 of 26 healthy adults a single 280 mg oral dose and 13 a placebo: MB increased fMRI responses in the bilateral insular cortex during a sustained-attention task and in prefrontal, parietal and occipital regions during a short-term memory task, with a 7% rise in correct answers in memory retrieval. The authors attributed the imaging changes more likely to higher oxygen use through mitochondrial respiration than to changes in blood flow or vascular tone.

What the Research Shows

Methylene blue has one of the longest research records of any drug — over 140 years. Modern clinical research clusters in: methemoglobinemia (approved indication), vasoplegic syndrome (adjunct), cognitive enhancement (exploratory human trials), and tau / Alzheimer's (LMTM derivative Phase III program).

• Methemoglobinemia reversal (FDA approval basis) — Decades of clinical experience; IV 1–2 mg/kg produces measurable methemoglobin reduction within minutes. Approved as ProvayBlue (Provepharm, NDA 204630, 2016) for acquired methemoglobinemia in adult and pediatric patients.
• fMRI memory retrieval (Rodriguez et al., Radiology 2016; PMID 27351678) — 26 healthy adults randomized to single-dose 280 mg oral MB vs placebo, assessed via fMRI during short-term memory tasks. MB increased activity in clusters in bilateral insular cortex and produced a ~7% improvement in memory retrieval.
• Spatial memory in rats (Callaway et al., Pharmacol Biochem Behav 2004) — In normal rats, 1 mg/kg MB injected after each daily training session improved spatial memory retention (66% vs 31% of visits to baited holes) and raised brain cytochrome c oxidation 24 hours after injection.
• Retention of extinction (Gonzalez-Lima and Bruchey, Learn Mem 2004) — Low-dose MB facilitated extinction memory retention in rats — a translationally relevant mechanism for anxiety and PTSD adjunct research.
• Vasoplegic syndrome (Levin et al., Ann Thorac Surg 2004; PMID 14759425) — Randomized trial of MB in vasoplegic syndrome after cardiopulmonary bypass; MB 1.5 mg/kg IV reduced mortality and shortened ICU stay compared to placebo. Standard-of-care adjunct in catecholamine-refractory vasodilatory shock.
• Ifosfamide encephalopathy (Pelgrims et al., Br J Cancer 2000) — MB reverses and prevents chemotherapy-induced ifosfamide encephalopathy in high-dose chemotherapy protocols.
• Alzheimer's — TauRx LMTM Phase III (Gauthier et al., Lancet 2016; PMID 27863809) — TRx-015 Phase III trial of LMTM in 891 patients with mild-to-moderate Alzheimer's; the primary analyses showed no benefit at either dose. In patients taking LMTM as monotherapy, a post-hoc analysis set out in the statistical plan suggested benefit. The follow-on LUCIDITY Phase III trial (TRx-237-039, NCT03446001) was completed in April 2023.
• Malaria treatment (Meissner et al., Malaria J 2006; PMID 17026773) — Uncontrolled dose-finding study of MB with chloroquine in 435 young children with falciparum malaria in Burkina Faso: MB appeared to have efficacy, but the MB–chloroquine combination was clearly not effective for malaria in Africa.
• Lifespan extension (Atamna et al., FASEB 2008; PMID 17928358) — In human IMR90 fibroblasts (cells that build collagen) in culture, methylene blue extended replicative life span by more than 20 population doublings, raised mitochondrial complex IV by 30% and cellular oxygen consumption by 37 to 70%, and reversed premature senescence caused by hydrogen peroxide or cadmium.
• Septic shock refractory to norepinephrine (Kirov et al., Crit Care Med 2001) — MB raises systemic vascular resistance in norepinephrine-refractory septic shock; use is contentious and not standard-of-care but has a signal.
• Parkinson's disease preclinical — A 2012 review describes MB protecting rodent retina and brain against rotenone, a complex I inhibitor used to model Parkinsonism, and attributes it to the mitochondrial electron-carrier mechanism (Rojas et al., 2012).
• Post-viral fatigue / long COVID (exploratory) — Small case series and uncontrolled reports suggest possible benefit for post-viral mitochondrial-dysfunction-type fatigue; no rigorous RCT data.

Human Data

Methylene blue human data spans acute-care use in methemoglobinemia and vasoplegia; investigational cognitive / imaging studies; and the LMTM derivative program in dementia.

• ProvayBlue FDA approval (NDA 204630, 2016) — The current label gives 1 mg/kg IV, with one repeat dose of up to 1 mg/kg an hour later if methemoglobin stays above 30% or symptoms persist, and reports two studies of 31 adults with acquired methemoglobinemia, most given 1 mg/kg: 26 of the 28 with a baseline level at least halved it by the first check (ProvayBlue label, 2025).
• Rodriguez et al. 2016 fMRI memory (PMID 27351678) — Randomized, double-blind, placebo-controlled fMRI study; 26 healthy adults; 280 mg oral single dose; memory retrieval and insular BOLD activity improvements.
• Levin 2004 vasoplegic syndrome RCT (PMID 14759425) — 56 patients with post-cardiopulmonary-bypass vasoplegic syndrome; MB 1.5 mg/kg IV reduced mortality and ICU stay.
• Gauthier 2016 TRx-015 Phase III AD (PMID 27863809) — 891 mild-moderate Alzheimer's patients; the primary analyses showed no benefit; a post-hoc analysis in patients taking LMTM as monotherapy suggested benefit.
• Peter 2000 MB pharmacokinetics (Eur J Clin Pharmacol) — In seven volunteers given 100 mg IV and by mouth, the terminal half-life after IV dosing was about 5.25 hours, blood exposure after oral dosing was much lower (AUC 9 vs 137 nmol/min/mL), and 28% of the IV dose and 18% of the oral dose were excreted in urine (Peter et al., 2000). A 2009 study cited in a review put oral bioavailability at 72.3% (Oz et al., 2011), and the current label gives a half-life of about 24 hours (ProvayBlue label, 2025).
• Kirsch 2019 MB in refractory shock (pooled cohort) — Real-world evidence for MB in catecholamine-resistant vasodilatory shock beyond cardiac surgery.
• Methemoglobinemia registries (various countries) — Long-running safety and efficacy data supporting indication persistence.
• LUCIDITY Phase III LMTM (TauRx, TRx-237-039; NCT03446001) — Confirmatory Phase III of LMTM in Alzheimer's completed 2023; topline results reported in 2024 did not clearly replicate prior monotherapy signal; regulatory strategy unresolved as of 2026.
• Photodynamic therapy studies (dental / dermatologic) — Multiple trials in periodontal disease, oral candidiasis, and superficial bacterial infection under red-light activation.

Reconstitution & Storage

Methylene blue is not a peptide, and nothing is mixed: ProvayBlue is a ready-made 5 mg/mL solution for IV use (ProvayBlue label, 2025). Compounding pharmacies list oral solutions (10 mg/mL or 50 mg/mL) and sublingual troches.

• Storage — ProvayBlue is stored at 20–25 °C (excursions 15–30 °C), not refrigerated or frozen, in its carton to protect it from light, and unused solution is discarded (ProvayBlue label, 2025).
• Blue discoloration — The label notes blue discoloration of the skin and body fluids (ProvayBlue label, 2025); green-blue urine, also seen in saliva, fades within a few days of stopping (Oz et al., 2011).
• Pulse oximetry artifact — Methylene blue in the blood can make pulse oximetry underestimate oxygen saturation; the label advises an arterial blood sample tested by another method (ProvayBlue label, 2025).
• Inspection — The label describes ProvayBlue as a clear dark blue solution and lists visual inspection for particles and discoloration before use (ProvayBlue label, 2025).

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Side Effects & Risks

Most lines below come from the label of ProvayBlue, the approved IV product; other sources are named.

• Serotonin syndrome (boxed warning) — The label warns that methylene blue may cause serious or fatal serotonin syndrome with serotonergic drugs and opioids; most reported cases involved SSRIs, SNRIs or MAOIs, opioids and dextromethorphan may raise the risk, and some cases were fatal (ProvayBlue label, 2025). FDA's 2011 communication said the mechanism is unknown but that methylene blue inhibits MAO-A; for planned treatment, it said most serotonergic psychiatric drugs should be stopped at least 2 weeks ahead (fluoxetine, at least 5 weeks) (FDA Drug Safety Communication, 2011). The current label advises against serotonergic drugs for 72 hours after the last dose (ProvayBlue label, 2025).
• Hemolytic anemia in G6PD deficiency — The label contraindicates methylene blue in G6PD deficiency: treatment may cause severe hemolysis and anemia, and the drug may not be converted to its active form, so it may not work (ProvayBlue label, 2025).
• Blue-green discoloration — The label notes blue discoloration of the skin and body fluids (ProvayBlue label, 2025); the green-blue color of urine, also seen in saliva, fades within a few days of stopping (Oz et al., 2011).
• Pulse oximetry interference — Methylene blue in the blood can make pulse oximetry underestimate oxygen saturation; the label advises an arterial blood sample tested by another method (ProvayBlue label, 2025).
• Methemoglobinemia and other overdose effects — The label reports mild methemoglobinemia (up to 7%), with nausea, chest pain, breathlessness and confusion, after large IV doses (cumulative 7 mg/kg or more); low blood pressure, wheezing and reduced oxygenation after single doses of 3 mg/kg or more; and severe hemolysis and death after single doses of 20 mg/kg or more (ProvayBlue label, 2025).
• Hemolysis (without G6PD deficiency) — Hemolysis can occur during treatment, with Heinz bodies, raised indirect bilirubin and low haptoglobin but a negative Coombs test; the anemia can appear a day or more later and may need transfusion (ProvayBlue label, 2025).
• Gut effects — Nausea and diarrhea were among the most common reactions (2% or more) in the label's 31 adults, and lower abdominal pain, dry mouth and flatulence are listed for methylene blue products (ProvayBlue label, 2025). In the LMTM Alzheimer's trial, gastrointestinal and urinary effects were the most common adverse events at the two higher doses (Gauthier et al., 2016).
• Headache, dizziness and confusion — Headache was among the most common reactions (2% or more) in the label's 31 adults, along with low potassium and magnesium, myoclonus and seizure-like events; the label also lists confusion, dizziness and disturbances in vision (ProvayBlue label, 2025).
• Hypertension — The label lists hypertension among reactions to methylene blue products (ProvayBlue label, 2025); nitric oxide synthase inhibition mediates its cardiovascular effects, the basis of its use in septic shock (Rojas et al., 2012).
• Anaphylaxis — Anaphylactic reactions to methylene blue products have been reported, and severe hypersensitivity to it or another thiazine dye is a contraindication (ProvayBlue label, 2025).
• Pregnancy and breastfeeding — The label says it may cause fetal harm: intra-amniotic injection in the second trimester was associated with intestinal atresia and fetal death, and oral doses harmed development in rats and rabbits. It advises use in pregnancy only if the benefit justifies the risk, and stopping breastfeeding for up to 8 days after treatment (ProvayBlue label, 2025).
• Newborns — Reported toxicities in neonates include hemolytic anemia, respiratory distress and phototoxicity (Oz et al., 2011); after intra-amniotic injection near birth, the label lists hyperbilirubinemia, hemolytic anemia, skin staining, methemoglobinemia, respiratory distress and photosensitivity in the newborn (ProvayBlue label, 2025).
• Chemical-grade product — Industrial- and chemical-grade methylene blue sold as a dye or stain can be more than 8% or 11% contaminants, and a 2012 review says it should not be given to humans or animals; it adds that even USP-grade methylene blue carries impurities such as arsenic, aluminum, cadmium, mercury and lead (Rojas et al., 2012).
• Mouth staining — Clinical oral use gives methylene blue in gelatin capsules, to avoid staining the mouth (Oz et al., 2011).
• Other interactions — Methylene blue products can lower Bispectral Index readings during anesthesia (ProvayBlue label, 2025), and MB lowers the minimum alveolar concentration of anesthetics such as sevoflurane and isoflurane (Oz et al., 2011). In a clinical cocktail study, a 2 mg/kg IV dose did not change exposure to midazolam, caffeine, warfarin or dextromethorphan (ProvayBlue label, 2025).

Bloodwork & Monitoring

No trial, label or guideline sets monitoring for low-dose oral methylene blue. For the approved IV product, the label lists watching for serotonin syndrome and anaphylaxis, following methemoglobin until it resolves, and longer monitoring in liver impairment, and it contraindicates use in G6PD deficiency (ProvayBlue label, 2025). The 2016 fMRI study excluded people with G6PD deficiency or psychiatric drug use in the previous 5 weeks (Rodriguez et al., 2016), and the LMTM Alzheimer's trial measured methemoglobin by pulse CO-oximetry (Gauthier et al., 2016).

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References

1. 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;281(2):516-526. PMID: 27351678. DOI: 10.1148/radiol.2016152893.
2. Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. FASEB J. 2008;22(3):703-712. PMID: 17928358. DOI: 10.1096/fj.07-9610com.
3. Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012;96(1):32-45. PMID: 22067440. DOI: 10.1016/j.pneurobio.2011.10.007.
4. Oz M, Lorke DE, Hasan M, Petroianu GA. Cellular and molecular actions of methylene blue in the nervous system. Med Res Rev. 2011;31(1):93-117. PMID: 19760660.
5. Bruchey AK, Gonzalez-Lima F. Behavioral, physiological and biochemical hormetic responses to the auto-oxidizable dye methylene blue. Am J Pharmacol Toxicol. 2008;3(1):72-79. PMC2867617.
6. Wischik CM, Edwards PC, Lai RY, Roth M, Harrington CR. Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A. 1996;93(20):11213-11218. PMID: 8855335.
7. Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, Hardlund JH, Moebius HJ, Bentham P, Kook KA, Wischik DJ, Schelter BO, Davis CS, Staff RT, Bracoud L, Shamsi K, Storey JM, Harrington CR, Wischik CM. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet. 2016;388(10062):2873-2884. PMID: 27863809.
8. Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW, Schwam E, Schindler R, Hey-Hadavi J, DeMicco DA, Breazna A; LEADe Investigators. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74(12):956-964. PMID: 20200346. (Complementary Alzheimer's methodology reference.)
9. Levin RL, Degrange MA, Bruno GF, Del Mazo CD, Taborda DJ, Griotti JJ, Boullon FJ. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg. 2004;77(2):496-499. PMID: 14759425.
10. Pelgrims J, De Vos F, Van den Brande J, Schrijvers D, Prové A, Vermorken JB. Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature. Br J Cancer. 2000;82(2):291-294. PMID: 10646879.
11. FDA. FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. U.S. Food and Drug Administration; July 26, 2011.
12. FDA. ProvayBlue (methylene blue) prescribing information. NDA 204630. Approved April 8, 2016. Provepharm.
13. 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;77(1):175-181. PMID: 14724055.
14. Meissner PE, Mandi G, Coulibaly B, Witte S, Tapsoba T, Mansmann U, Rengelshausen J, Schiek W, Jahn A, Walter-Sack I, Mikus G, Burhenne J, Riedel KD, Schirmer RH, Kouyaté B, Müller O. Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malar J. 2006;5:84. PMID: 17026773.
15. Peter C, Hongwan D, Küpfer A, Lauterburg BH. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol. 2000;56(3):247-250. PMID: 10952480.
16. Schirmer RH, Adler H, Pickhardt M, Mandelkow E. Lest we forget you — methylene blue... Neurobiol Aging. 2011;32(12):2325.e7-2325.e16. PMID: 21316815.
17. Küpfer A, Aeschlimann C, Wermuth B, Cerny T. Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue. Lancet. 1994;343(8900):763-764. PMID: 7510815.
18. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)
19. Provepharm SAS; American Regent, Inc. ProvayBlue (methylene blue) injection, USP prescribing information. DailyMed set ID 4f6848e5-35ed-4046-b13c-3032b5ba3232, version effective May 28, 2025. dailymed.nlm.nih.gov. Read October 4, 2026.
20. Doganay S, Üstündağ H, Erbaş E, Yanar S, Hayme S, Kurt N. Assessment of methylene blue and NAD on LPS-induced acute brain injury: effects on neuroinflammation, oxidative stress, and blood-brain barrier integrity in a rat endotoxemia model. Naunyn Schmiedebergs Arch Pharmacol. 2026;399(11):17239-17254. PMID: 42165863.
21. Gonzalez-Lima F, Bruchey AK. Extinction memory improvement by the metabolic enhancer methylene blue. Learn Mem. 2004;11(5):633-640. PMID: 15466319. DOI: 10.1101/lm.82404.

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