Comparison
Citicoline vs Low-Dose Naltrexone
Side-by-side of Citicoline and Low-Dose Naltrexone. 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.
Citicoline
Citicoline supplement profile: CDP-choline as a phosphatidylcholine precursor, Cognizin dosing 250-2000 mg, cognition trials, stroke recovery evidence.
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.
Effects at a glance
Citicoline
- •Choline donor and phosphatidylcholine precursor; oral bioavailability roughly 99%
- •Standard prescription medication for stroke recovery and vascular cognitive impairment in much of the world
- •Healthy-adult cognitive trials (Cognizin) report small gains in attention and working memory at 250 to 500 mg/day
- •ICTUS trial (n=2,298) was negative on stroke recovery in the modern thrombolysis era
- •Lower per-gram choline content than alpha-GPC (~18% vs ~40%), meaning smaller TMAO load at equivalent dose
- •Long uridine half-life (~56 hours) supports once or twice daily dosing
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
Side-by-side
| Attribute | Citicoline | Low-Dose Naltrexone |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | CDP-choline, cytidine 5'-diphosphocholine, Cognizin | LDN, naltrexone (low dose) |
| Half-life (hr) ↗ | 56 | 4 |
| Typical dose (mg) ↗ | 500 | 4.5 |
| Dosing frequency | 1 to 2 times daily | once daily, typically at bedtime |
| Routes | oral, intravenous | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 2 | 1.5 |
| Molecular weight | 488.32 | 341.4 |
| Molecular formula | C14H26N4O11P2 | C20H23NO4 |
| Mechanism | Hydrolyzed to cytidine and choline after absorption; both cross the blood-brain barrier and are recombined intracellularly to reform CDP-choline, supporting phosphatidylcholine synthesis and acetylcholine production. | 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. |
| Legal status | Dietary supplement (US, Cognizin GRAS); prescription medication in most of the world | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement (US); Rx in most of the world | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data for routine use | Insufficient data; not routinely recommended |
| CAS | 987-78-0 | 16590-41-3 |
| PubChem CID | 13804 | 5360515 |
| Wikidata | Q411470 | Q426444 |
Safety profile
Citicoline
Common side effects
- mild GI upset
- headache
- restlessness
- occasional insomnia with evening dosing
Contraindications
- concurrent strong anticholinergic therapy
- established cardiovascular disease (TMAO concern, smaller than alpha-GPC)
Interactions
- anticholinergic medications: partial mutual antagonism(minor)
- cholinesterase inhibitors: additive cholinergic effect(minor)
- antimetabolite chemotherapy (5-FU): theoretical cytidine pathway interaction(minor)
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)
Which Should You Take?
Citicoline comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. Low-Dose Naltrexone is the right call when one of the conditionals below applies.
- → If your priority is focus or working memory, pick Citicoline.
- → If your priority is stroke recovery, pick Citicoline.
- → If your priority is immune support, pick Low-Dose Naltrexone.
- → If your priority is pain modulation, pick Low-Dose Naltrexone.
Edge case: If you want to avoid prescription-only, Citicoline is the more accessible choice.
Default choice: Citicoline. Lower friction to source, 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 Citicoline and Low-Dose Naltrexone?
Citicoline and Low-Dose Naltrexone 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, Citicoline or Low-Dose Naltrexone?
Citicoline half-life is 56 hours; Low-Dose Naltrexone half-life is 4 hours.
Can you stack Citicoline with Low-Dose Naltrexone?
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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