Comparison
Methylene Blue vs Modafinil
Side-by-side of Methylene Blue and Modafinil. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Methylene Blue
Methylene blue as a nootropic: low-dose cognitive enhancement, mitochondrial electron cycling, brain oxygen uptake, SSRI interaction risk, typical 0.5 to 4 mg.
Modafinil
Modafinil cognitive enhancement profile: wakefulness-promoting agent, 100-200 mg dosing, 12-15 hour half-life, off-label nootropic use, Schedule IV status.
Effects at a glance
Methylene Blue
- •FDA approved for methemoglobinemia and ifosfamide-induced encephalopathy
- •Mitochondrial electron-transport support at low doses (0.5 to 4 mg/kg) via cytochrome c shuttle
- •Potent MAO-A inhibitor; serotonin syndrome risk with SSRIs, SNRIs, MAOIs, fentanyl, tramadol, St John's wort
- •Causes harmless blue-green urine and sweat coloration; useful adherence marker
- •G6PD deficiency is an absolute contraindication; can trigger massive hemolysis
- •Cognitive-enhancement evidence is preliminary, mostly preclinical and small fMRI trials
Modafinil
- •FDA approved in 1998 for narcolepsy, with later additions for shift-work sleep disorder and OSA residual sleepiness
- •Schedule IV controlled substance in the US; prescription-only in EU, UK, Australia
- •Increases wakefulness via weak dopamine reuptake inhibition plus histaminergic, noradrenergic, and orexinergic activation
- •Long half-life of 12 to 15 hours requires morning dosing to avoid sleep disruption
- •Modest cognitive enhancement signal in non-sleep-deprived adults at 100 to 200 mg (Battleday meta-review 2015)
- •Substantial CYP3A4 induction reduces hormonal contraceptive efficacy; barrier methods recommended
Side-by-side
| Attribute | Methylene Blue | Modafinil |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | Methylthioninium chloride, Provayblue, tetramethylthionine chloride | Provigil, Modalert, Modvigil, diphenylmethylsulfinyl-acetamide |
| Half-life (hr) ↗ | 5.5 | 13 |
| Typical dose (mg) ↗ | 70 | 200 |
| Dosing frequency | 1 to 3 times daily for cognitive use; single IV dose for methemoglobinemia | daily, morning |
| Routes | oral, intravenous | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 1.5 | 3 |
| Molecular weight | 319.85 | 273.35 |
| Molecular formula | C16H18ClN3S | C15H15NO2S |
| Mechanism | Mitochondrial electron carrier at low doses (cytochrome c shuttle to complex IV) and methemoglobin reductase substrate at higher doses; potent MAO-A inhibitor across the dose range. | Weak dopamine reuptake inhibition plus downstream activation of histaminergic, noradrenergic, and orexinergic wake-promoting systems. |
| Legal status | Prescription (injectable, FDA approved); supplement form (oral) widely available; not scheduled | Schedule IV (US); prescription-only globally; not a supplement |
| WADA status | allowed | banned |
| DEA / Rx | Not scheduled in the US | Schedule IV |
| Pregnancy | Contraindicated | Not recommended |
| CAS | 61-73-4 | 68693-11-8 |
| PubChem CID | 6099 | 4236 |
| Wikidata | Q409021 | Q422968 |
Safety profile
Methylene Blue
Common side effects
- blue-green urine and sweat
- skin and oral mucosa staining
- GI upset
- headache
- dizziness
Contraindications
- G6PD deficiency
- pregnancy
- concurrent serotonergic medication
- severe renal impairment
- infants under 6 months
Interactions
- SSRIs and SNRIs: serotonin syndrome, potentially fatal(major)
- MAOIs: additive MAO inhibition, serotonin syndrome risk(major)
- fentanyl, tramadol, meperidine: serotonin syndrome risk(major)
- dextromethorphan: serotonin syndrome risk(major)
- St John's wort: serotonin syndrome risk(major)
- lithium: additive serotonergic risk(major)
Modafinil
Common side effects
- headache
- nausea
- anxiety
- insomnia (with late-day dosing)
- dry mouth
- mild blood pressure elevation
Contraindications
- recent myocardial infarction
- unstable angina
- left ventricular hypertrophy
- significant arrhythmia
- history of Stevens-Johnson syndrome
- psychotic disorders
- pregnancy
- concurrent MAOI use
Interactions
- hormonal contraceptives: CYP3A4 induction reduces contraceptive efficacy; use barrier method(major)
- cyclosporine: reduced cyclosporine levels via CYP3A4 induction(major)
- warfarin: CYP2C9 inhibition raises INR(moderate)
- phenytoin: CYP2C19 inhibition raises phenytoin levels(moderate)
- MAOIs: potential hypertensive reaction(major)
- classical stimulants (amphetamine, methylphenidate): additive cardiovascular and sleep-disruption effects(moderate)
Which Should You Take?
Methylene Blue and Modafinil score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is mitochondrial function, pick Methylene Blue.
- → If your priority is antimicrobial action, pick Methylene Blue.
- → If your priority is wakefulness, pick Modafinil.
- → If your priority is fatigue resistance, pick Modafinil.
Edge case: Methylene Blue is contraindicated in pregnancy; Modafinil is the safer pick if that applies.
Default choice: either is defensible. Methylene Blue edges out on goal breadth + legal accessibility; Modafinil is the right call if your priority sits in the goals listed above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Methylene Blue and Modafinil?
Methylene Blue and Modafinil differ in category (pharmaceutical vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Methylene Blue or Modafinil?
Methylene Blue half-life is 5.5 hours; Modafinil half-life is 13 hours.
Can you stack Methylene Blue with Modafinil?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper