Comparison
Melatonin vs Rapamycin
Side-by-side of Melatonin and Rapamycin. 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.
Rapamycin
Rapamycin for longevity: sirolimus, an mTOR inhibitor with ITP mouse lifespan data. Off-label geroprotective dosing remains investigational.
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
Rapamycin
- •Inhibits mTORC1 signaling by binding FKBP12, reducing protein synthesis and relieving autophagy suppression
- •ITP mouse program reproduced lifespan extension of ~10 to 25% across multiple genetic backgrounds and sexes
- •Mannick trials showed improved influenza vaccine response in elderly adults using analogs of rapamycin
- •PEARL human trial reported acceptable safety at 5 to 10 mg weekly with some functional and lean-mass signals
- •Common dose-limiting adverse effects include stomatitis, acne-like rash, and mildly elevated lipid markers
- •CYP3A4 substrate: grapefruit, ketoconazole, and clarithromycin substantially raise rapamycin exposure
Side-by-side
| Attribute | Melatonin | Rapamycin |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | N-acetyl-5-methoxytryptamine | Sirolimus, Rapamune |
| Half-life (hr) ↗ | 0.75 | 62 |
| Typical dose (mg) ↗ | 0.5 | 6 |
| Dosing frequency | daily, 30 to 60 minutes before target sleep time | weekly (longevity protocols); daily for transplant indication |
| Routes | oral, sublingual | oral |
| Onset (hr) | 0.5 | 1 |
| Peak (hr) | 1 | 2 |
| Molecular weight | 232.28 | 914.17 |
| Molecular formula | C13H16N2O2 | C51H79NO13 |
| Mechanism | Agonist at MT1 and MT2 receptors in the suprachiasmatic nucleus, signaling biological night and promoting sleep-onset gating plus circadian phase shifts. | Binds FKBP12, and the resulting complex inhibits mTORC1, reducing protein synthesis and autophagy suppression downstream of nutrient and growth-factor signaling. |
| Legal status | OTC in US; prescription in UK, EU, Japan | Prescription only (off-label for longevity) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement in US; Rx in UK, EU, Japan, Australia | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data; not routinely recommended | Not recommended |
| CAS | 73-31-4 | 53123-88-9 |
| PubChem CID | 896 | 5284616 |
| Wikidata | Q179243 | Q410174 |
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)
Rapamycin
Common side effects
- mouth ulcers (stomatitis)
- acne-like rash
- GI upset
- altered lipid panel
- delayed wound healing
Contraindications
- active infection
- severe hepatic impairment
- planned surgery (delayed wound healing)
- pregnancy
- live vaccines within dosing window
Interactions
- strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit): substantially raises rapamycin levels, toxicity risk(major)
- strong CYP3A4 inducers (rifampin, St John's wort): lowers rapamycin levels, reduced effect(major)
- ACE inhibitors: increased risk of angioedema(moderate)
- live vaccines: reduced vaccine efficacy due to immunosuppression(major)
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. Rapamycin 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 healthspan extension, pick Rapamycin.
- → If your priority is immune support, pick Rapamycin.
Edge case: If you want to avoid prescription-only, Melatonin is the more accessible choice.
Default choice: Melatonin. Wider use case, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for Rapamycin 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 Rapamycin?
Melatonin and Rapamycin 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 Rapamycin?
Melatonin half-life is 0.75 hours; Rapamycin half-life is 62 hours.
Can you stack Melatonin with Rapamycin?
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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