Comparison
Modafinil vs Spermidine
Side-by-side of Modafinil and Spermidine. 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.
Modafinil
Modafinil cognitive enhancement profile: wakefulness-promoting agent, 100-200 mg dosing, 12-15 hour half-life, off-label nootropic use, Schedule IV status.
Spermidine
Spermidine supplement benefits cover autophagy induction, longevity signals, and cognition. Wheat germ extract data, doses, and human trials reviewed.
Effects at a glance
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
Spermidine
- •Endogenous polyamine that induces autophagy via EP300 acetyltransferase inhibition and TFEB activation
- •Concentrated in wheat germ, soybeans, aged cheese, and mushrooms; ~10 to 15 mg/day in Mediterranean diets
- •Eisenberg 2016 reported dietary spermidine extended mouse lifespan and improved cardiac function
- •Wirth 2018 pilot (n=28) reported cognitive signal at 0.9 mg/day in older adults at risk for dementia
- •Larger Wirth 2019 follow-up (n=85) did not replicate the memory benefit at 12 months
- •Generally regarded as safe at supplemental doses; food-source position is reassuring
Side-by-side
| Attribute | Modafinil | Spermidine |
|---|---|---|
| Category | pharmaceutical | supplement |
| Also known as | Provigil, Modalert, Modvigil, diphenylmethylsulfinyl-acetamide | spermidine trihydrochloride, wheat-germ-extract spermidine |
| Half-life (hr) ↗ | 13 | 6 |
| Typical dose (mg) ↗ | 200 | 1.2 |
| Dosing frequency | daily, morning | daily, typically morning with food |
| Routes | oral | oral |
| Onset (hr) | 1 | 2 |
| Peak (hr) | 3 | 4 |
| Molecular weight | 273.35 | 145.25 |
| Molecular formula | C15H15NO2S | C7H19N3 |
| Mechanism | Weak dopamine reuptake inhibition plus downstream activation of histaminergic, noradrenergic, and orexinergic wake-promoting systems. | Induces macroautophagy via inhibition of EP300 histone acetyltransferase and activation of TFEB-mediated lysosomal biogenesis. Substrate for hypusination of eIF5A, required for translation of mitochondrial respiration proteins. |
| Legal status | Schedule IV (US); prescription-only globally; not a supplement | OTC dietary supplement (wheat-germ extract has GRAS status in US) |
| WADA status | banned | allowed |
| DEA / Rx | Schedule IV | OTC supplement (not scheduled) |
| Pregnancy | Not recommended | Insufficient data; not routinely recommended at supplemental doses |
| CAS | 68693-11-8 | 124-20-9 |
| PubChem CID | 4236 | 1102 |
| Wikidata | Q422968 | Q411089 |
Safety profile
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)
Spermidine
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- wheat-germ allergy or celiac disease (for wheat-germ-extract products)
- active cancer (theoretical)
- pregnancy and lactation (insufficient data)
Interactions
- DFMO (difluoromethylornithine): competing polyamine metabolism; do not combine without oncology guidance(moderate)
Which Should You Take?
Spermidine comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. Modafinil is the right call when one of the conditionals below applies.
- → If your priority is wakefulness, pick Modafinil.
- → If your priority is fatigue resistance, pick Modafinil.
- → If your priority is healthspan extension, pick Spermidine.
Edge case: If you want to avoid controlled substance, Spermidine is the more accessible choice.
Default choice: Spermidine. Lower friction to source, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for Modafinil only if your priority sits squarely in the goals it owns 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 Modafinil and Spermidine?
Modafinil and Spermidine differ in category (pharmaceutical vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Modafinil or Spermidine?
Modafinil half-life is 13 hours; Spermidine half-life is 6 hours.
Can you stack Modafinil with Spermidine?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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