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Monograph
FDA APPROVEDT-002
Cognition

Methylene Blue

Phenothiazine dye + electron-cycling agent. FDA-approved IV antidote for methemoglobinemia. Off-label uses span mitochondrial-energy + cognitive-enhancement protocols at controversial sub-therapeutic doses.

EmergingCognition
Typical dose0.5-4 mg (sub-therapeutic, off-label)
Frequencymorning oral; never with SSRIs, SNRIs, or MAOIs
Half-life5h
Citations indexed38
DeliveryOral
Half-life~5h
EvidenceEmerging
Citations38
Similar compounds
Synergy checkCompare
Mechanism

MB acts as electron donor + acceptor in the mitochondrial electron transport chain (donates to complex IV / cytochrome c oxidase). Approved IV indication is severe methemoglobinemia at 1-2 mg/kg. Off-label cognitive-enhancement cohort uses sub-therapeutic oral doses (0.5-4 mg/day) based on rodent neuroprotection literature + Bryan Johnson protocol popularization. The leap from rodent model to oral microdose efficacy in healthy humans is inadequately validated. Stack catalogs MB for SAFETY interaction surface — serotonin syndrome with SSRIs is the real risk users encounter.

Specifics
Focus / attentionLow energy / fatigue
Field reports

Distilled themes from named communities — Reddit threads, forums, creator commentary. Not direct quotes; not clinical evidence. Useful for calibrating expectations against what real self-experimenters report.

r/Nootropics + Bryan Johnson DD adoption threads

Cohort splits sharply: Bryan Johnson DD followers report subjective cognitive lift at 2-4 mg oral; mainstream-medicine cohort points to inadequate human evidence + serotonin syndrome risk. Stack documents both honestly + flags the SSRI interaction explicitly.

Caveats

HARD CONTRAINDICATION — concurrent SSRIs / SNRIs / MAOIs / TCAs (serotonin syndrome can be fatal; FDA boxed warning 2011). G6PD deficiency = hard contraindication (hemolysis). Stains everything blue — urine, sweat, contact lenses. Pharmaceutical-grade USP MB only — industrial / aquarium-grade contains heavy metals. Bryan Johnson popularization has driven dosing-creep + casual self-experimentation; the cognitive-enhancement evidence base does NOT support this.

Evidence levelEmerging
Regulatory statusFDA-approved IV (methemoglobinemia, cyanide poisoning adjunct). Oral form sold as compounded prep or USP-grade powder; off-label cognitive use lacks FDA endorsement.
DNA / pharmacogenomicsLow — G6PD deficiency is a hard contraindication — MB induces hemolysis. ~10-15% of African + Mediterranean ancestry has G6PD deficiency; routine pre-screen is required if dosing IV.
References

External links to PubMed searches, ClinicalTrials.gov, and FDA materials. We do not host papers — we point at canonical sources.

  • RegulatoryEN
    REGULATORYNIH-fundedVerified 3d ago
    FDA — Methylene Blue serotonin-syndrome boxed warning (2011)
  • PubMedEN
    REVIEWAcademic-fundedVerified 3d ago
    Rojas JC et al. — Methylene blue neuroprotection rodent literature (Prog Neurobiol 2012)
  • PubMedEN
    RCTAcademic-fundedVerified 3d ago
    Telch MJ et al. — Methylene blue + extinction memory consolidation human RCT (J Psychiatr Res 2014)
FDA APPROVEDT-002

FDA-approved IV (methemoglobinemia, cyanide poisoning adjunct). Oral form sold as compounded prep or USP-grade powder; off-label cognitive use lacks FDA endorsement.

Methylene Blue0.5-4 mg (sub-therapeutic, off-label) · morning oral; never with SSRIs, SNRIs, or MAOIs
Discussion guide, not prescription

stack is an exploration engine. Output is a discussion guide for a conversation with a licensed provider — never a prescription, dose recommendation, or sourcing instruction. Peptides discussed include compounds with limited human evidence and varying legal status by jurisdiction. Verify everything with a qualified clinician before any decision.

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