Comparison
Low-Dose Naltrexone vs Modafinil
Side-by-side of Low-Dose Naltrexone 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.
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.
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
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
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 | Low-Dose Naltrexone | Modafinil |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | LDN, naltrexone (low dose) | Provigil, Modalert, Modvigil, diphenylmethylsulfinyl-acetamide |
| Half-life (hr) ↗ | 4 | 13 |
| Typical dose (mg) ↗ | 4.5 | 200 |
| Dosing frequency | once daily, typically at bedtime | daily, morning |
| Routes | oral | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 1.5 | 3 |
| Molecular weight | 341.4 | 273.35 |
| Molecular formula | C20H23NO4 | C15H15NO2S |
| 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. | Weak dopamine reuptake inhibition plus downstream activation of histaminergic, noradrenergic, and orexinergic wake-promoting systems. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Schedule IV (US); prescription-only globally; not a supplement |
| WADA status | allowed | banned |
| DEA / Rx | Rx only (not a controlled substance) | Schedule IV |
| Pregnancy | Insufficient data; not routinely recommended | Not recommended |
| CAS | 16590-41-3 | 68693-11-8 |
| PubChem CID | 5360515 | 4236 |
| Wikidata | Q426444 | Q422968 |
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)
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?
Modafinil comes out ahead for most readers on the criteria we weight: 3 catalogued goals, controlled substance, 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 wakefulness, pick Modafinil.
- → If your priority is focus or working memory, pick Modafinil.
Edge case: Half-lives differ materially (Low-Dose Naltrexone ~4 hr vs Modafinil ~13 hr). Modafinil reaches steady state faster; Low-Dose Naltrexone is easier to dial in if tolerability is uncertain.
Default choice: Modafinil. 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 Modafinil?
Low-Dose Naltrexone and Modafinil 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 Modafinil?
Low-Dose Naltrexone half-life is 4 hours; Modafinil half-life is 13 hours.
Can you stack Low-Dose Naltrexone 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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