Comparison
Low-Dose Naltrexone vs Melatonin
Side-by-side of Low-Dose Naltrexone and Melatonin. 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.
Melatonin
Melatonin as a sleep supplement: 0.3-1 mg matches physiological output, 3-10 mg is pharmacological. Shifts circadian phase, shortens sleep latency.
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
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
Side-by-side
| Attribute | Low-Dose Naltrexone | Melatonin |
|---|---|---|
| Category | pharmaceutical | supplement |
| Also known as | LDN, naltrexone (low dose) | N-acetyl-5-methoxytryptamine |
| Half-life (hr) ↗ | 4 | 0.75 |
| Typical dose (mg) ↗ | 4.5 | 0.5 |
| Dosing frequency | once daily, typically at bedtime | daily, 30 to 60 minutes before target sleep time |
| Routes | oral | oral, sublingual |
| Onset (hr) | 1 | 0.5 |
| Peak (hr) | 1.5 | 1 |
| Molecular weight | 341.4 | 232.28 |
| Molecular formula | C20H23NO4 | C13H16N2O2 |
| 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. | Agonist at MT1 and MT2 receptors in the suprachiasmatic nucleus, signaling biological night and promoting sleep-onset gating plus circadian phase shifts. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | OTC in US; prescription in UK, EU, Japan |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | OTC supplement in US; Rx in UK, EU, Japan, Australia |
| Pregnancy | Insufficient data; not routinely recommended | Insufficient data; not routinely recommended |
| CAS | 16590-41-3 | 73-31-4 |
| PubChem CID | 5360515 | 896 |
| Wikidata | Q426444 | Q179243 |
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)
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)
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. Low-Dose Naltrexone is the right call when one of the conditionals below applies.
- → If your priority is immune support, pick Low-Dose Naltrexone.
- → If your priority is pain modulation, pick Low-Dose Naltrexone.
- → If your priority is sleep onset or sleep quality, pick Melatonin.
- → If your priority is circadian regulation, pick Melatonin.
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 Low-Dose Naltrexone 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 Low-Dose Naltrexone and Melatonin?
Low-Dose Naltrexone and Melatonin 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, Low-Dose Naltrexone or Melatonin?
Low-Dose Naltrexone half-life is 4 hours; Melatonin half-life is 0.75 hours.
Can you stack Low-Dose Naltrexone with Melatonin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper