Comparison
Low-Dose Naltrexone vs Methylene Blue
Side-by-side of Low-Dose Naltrexone and Methylene Blue. 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.
Methylene Blue
Methylene blue as a nootropic: low-dose cognitive enhancement, mitochondrial electron cycling, brain oxygen uptake, SSRI interaction risk, typical 0.5 to 4 mg.
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
Methylene Blue
- •FDA approved for methemoglobinemia and ifosfamide-induced encephalopathy
- •Mitochondrial electron-transport support at low doses (0.5 to 4 mg/kg) via cytochrome c shuttle
- •Potent MAO-A inhibitor; serotonin syndrome risk with SSRIs, SNRIs, MAOIs, fentanyl, tramadol, St John's wort
- •Causes harmless blue-green urine and sweat coloration; useful adherence marker
- •G6PD deficiency is an absolute contraindication; can trigger massive hemolysis
- •Cognitive-enhancement evidence is preliminary, mostly preclinical and small fMRI trials
Side-by-side
| Attribute | Low-Dose Naltrexone | Methylene Blue |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | LDN, naltrexone (low dose) | Methylthioninium chloride, Provayblue, tetramethylthionine chloride |
| Half-life (hr) ↗ | 4 | 5.5 |
| Typical dose (mg) ↗ | 4.5 | 70 |
| Dosing frequency | once daily, typically at bedtime | 1 to 3 times daily for cognitive use; single IV dose for methemoglobinemia |
| Routes | oral | oral, intravenous |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 1.5 | 1.5 |
| Molecular weight | 341.4 | 319.85 |
| Molecular formula | C20H23NO4 | C16H18ClN3S |
| 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. | Mitochondrial electron carrier at low doses (cytochrome c shuttle to complex IV) and methemoglobin reductase substrate at higher doses; potent MAO-A inhibitor across the dose range. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Prescription (injectable, FDA approved); supplement form (oral) widely available; not scheduled |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Not scheduled in the US |
| Pregnancy | Insufficient data; not routinely recommended | Contraindicated |
| CAS | 16590-41-3 | 61-73-4 |
| PubChem CID | 5360515 | 6099 |
| Wikidata | Q426444 | Q409021 |
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)
Methylene Blue
Common side effects
- blue-green urine and sweat
- skin and oral mucosa staining
- GI upset
- headache
- dizziness
Contraindications
- G6PD deficiency
- pregnancy
- concurrent serotonergic medication
- severe renal impairment
- infants under 6 months
Interactions
- SSRIs and SNRIs: serotonin syndrome, potentially fatal(major)
- MAOIs: additive MAO inhibition, serotonin syndrome risk(major)
- fentanyl, tramadol, meperidine: serotonin syndrome risk(major)
- dextromethorphan: serotonin syndrome risk(major)
- St John's wort: serotonin syndrome risk(major)
- lithium: additive serotonergic risk(major)
Which Should You Take?
Methylene Blue 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 focus or working memory, pick Methylene Blue.
- → If your priority is mitochondrial function, pick Methylene Blue.
Edge case: Methylene Blue is contraindicated in pregnancy; Low-Dose Naltrexone is the safer pick if that applies.
Default choice: Methylene Blue. 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 Methylene Blue?
Low-Dose Naltrexone and Methylene Blue 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 Methylene Blue?
Low-Dose Naltrexone half-life is 4 hours; Methylene Blue half-life is 5.5 hours.
Can you stack Low-Dose Naltrexone with Methylene Blue?
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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