Comparison
Melatonin vs Modafinil
Side-by-side of Melatonin 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.
Melatonin
Melatonin as a sleep supplement: 0.3-1 mg matches physiological output, 3-10 mg is pharmacological. Shifts circadian phase, shortens sleep latency.
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
Melatonin
- •Shortens sleep onset latency by ~7 to 12 minutes at physiological 0.3 to 1 mg doses
- •Advances circadian phase when taken 30 to 60 minutes before target bedtime, useful for jet lag and shift work
- •Does not meaningfully increase total sleep time in healthy adults without circadian misalignment
- •Endogenous nighttime production is not suppressed by short-term exogenous supplementation
- •Higher doses (3 to 10 mg) raise plasma levels above physiological range and often increase morning grogginess
- •Effective for delayed sleep-wake phase disorder and reducing jet-lag severity in eastward travel
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 | Melatonin | Modafinil |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | N-acetyl-5-methoxytryptamine | Provigil, Modalert, Modvigil, diphenylmethylsulfinyl-acetamide |
| Half-life (hr) ↗ | 0.75 | 13 |
| Typical dose (mg) ↗ | 0.5 | 200 |
| Dosing frequency | daily, 30 to 60 minutes before target sleep time | daily, morning |
| Routes | oral, sublingual | oral |
| Onset (hr) | 0.5 | 1 |
| Peak (hr) | 1 | 3 |
| Molecular weight | 232.28 | 273.35 |
| Molecular formula | C13H16N2O2 | C15H15NO2S |
| Mechanism | Agonist at MT1 and MT2 receptors in the suprachiasmatic nucleus, signaling biological night and promoting sleep-onset gating plus circadian phase shifts. | Weak dopamine reuptake inhibition plus downstream activation of histaminergic, noradrenergic, and orexinergic wake-promoting systems. |
| Legal status | OTC in US; prescription in UK, EU, Japan | Schedule IV (US); prescription-only globally; not a supplement |
| WADA status | allowed | banned |
| DEA / Rx | OTC supplement in US; Rx in UK, EU, Japan, Australia | Schedule IV |
| Pregnancy | Insufficient data; not routinely recommended | Not recommended |
| CAS | 73-31-4 | 68693-11-8 |
| PubChem CID | 896 | 4236 |
| Wikidata | Q179243 | Q422968 |
Safety profile
Melatonin
Common side effects
- vivid dreams
- morning grogginess (higher doses)
- headache
- dizziness
Contraindications
- autoimmune disease (theoretical)
- concurrent anticoagulant therapy without monitoring
Interactions
- fluvoxamine: CYP1A2 inhibition raises melatonin levels substantially(major)
- warfarin: possible increased bleeding risk(moderate)
- benzodiazepines and alcohol: additive sedation(moderate)
- antihypertensives: may alter blood pressure response(minor)
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?
Melatonin comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC, oral dosing, with a Tier-A outcome catalogued. Modafinil is the right call when one of the conditionals below applies.
- → If your priority is sleep onset or sleep quality, pick Melatonin.
- → If your priority is circadian regulation, pick Melatonin.
- → If your priority is wakefulness, pick Modafinil.
- → If your priority is focus or working memory, pick Modafinil.
Edge case: If you want to avoid controlled substance, Melatonin is the more accessible choice.
Default choice: Melatonin. Wider use case, 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 Melatonin and Modafinil?
Melatonin and Modafinil differ in category (supplement vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Melatonin or Modafinil?
Melatonin half-life is 0.75 hours; Modafinil half-life is 13 hours.
Can you stack Melatonin with Modafinil?
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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