Comparison
Low-Dose Naltrexone vs Rapamycin
Side-by-side of Low-Dose Naltrexone 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.
Low-Dose Naltrexone
Low dose naltrexone at 1.5 to 4.5 mg, one-tenth the 50 mg addiction dose. Compounded Rx. Small trials in fibromyalgia, Crohn's, Hashimoto's.
Rapamycin
Rapamycin for longevity: sirolimus, an mTOR inhibitor with ITP mouse lifespan data. Off-label geroprotective dosing remains investigational.
Effects at a glance
Low-Dose Naltrexone
- •Off-label use at 1.5 to 4.5 mg, roughly one-tenth the FDA-approved 50 mg addiction-treatment dose
- •Proposed mechanisms include brief opioid receptor blockade triggering rebound endogenous opioid release, plus TLR4 antagonism
- •Compounded prescription only; insurance rarely covers; cash prices 20 to 80 USD per month
- •Younger 2013 reported ~30% pain reduction in fibromyalgia at 4.5 mg in a small crossover trial
- •Smith 2011 reported endoscopic improvement in active Crohn's disease (n=40 placebo-controlled)
- •Vivid dreams affect 20 to 40% in first 2 weeks; manageable by switching to morning dosing
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 | Low-Dose Naltrexone | Rapamycin |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | LDN, naltrexone (low dose) | Sirolimus, Rapamune |
| Half-life (hr) ↗ | 4 | 62 |
| Typical dose (mg) ↗ | 4.5 | 6 |
| Dosing frequency | once daily, typically at bedtime | weekly (longevity protocols); daily for transplant indication |
| Routes | oral | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 1.5 | 2 |
| Molecular weight | 341.4 | 914.17 |
| Molecular formula | C20H23NO4 | C51H79NO13 |
| Mechanism | Brief mu-opioid receptor antagonism proposed to trigger compensatory upregulation of endogenous opioids; secondary TLR4 antagonism on microglia and immune cells contributes to anti-inflammatory effect. | Binds FKBP12, and the resulting complex inhibits mTORC1, reducing protein synthesis and autophagy suppression downstream of nutrient and growth-factor signaling. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Prescription only (off-label for longevity) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data; not routinely recommended | Not recommended |
| CAS | 16590-41-3 | 53123-88-9 |
| PubChem CID | 5360515 | 5284616 |
| Wikidata | Q426444 | Q410174 |
Safety profile
Low-Dose Naltrexone
Common side effects
- vivid dreams
- sleep disruption
- headache
- mild GI upset
- fatigue (early)
Contraindications
- concurrent opioid use
- acute hepatitis or liver failure
- opioid dependence
- pregnancy (insufficient data)
Interactions
- opioid analgesics (oxycodone, morphine, codeine): blocks analgesic effect; precipitates withdrawal in dependent users(major)
- tramadol: blocks opioid component of analgesia(major)
- thyroid hormone replacement: may alter dose requirements after immune modulation; monitor TSH(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?
Low-Dose Naltrexone and Rapamycin 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 pain modulation, pick Low-Dose Naltrexone.
- → If your priority is healthspan extension, pick Rapamycin.
- → If your priority is immune support, pick Low-Dose Naltrexone.
Edge case: Half-lives differ materially (Low-Dose Naltrexone ~4 hr vs Rapamycin ~62 hr). Rapamycin reaches steady state faster; Low-Dose Naltrexone is easier to dial in if tolerability is uncertain.
Default choice: either is defensible. Low-Dose Naltrexone edges out on goal breadth + legal accessibility; Rapamycin 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 Low-Dose Naltrexone and Rapamycin?
Low-Dose Naltrexone and Rapamycin 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, Low-Dose Naltrexone or Rapamycin?
Low-Dose Naltrexone half-life is 4 hours; Rapamycin half-life is 62 hours.
Can you stack Low-Dose Naltrexone with Rapamycin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper