Comparison
Low-Dose Naltrexone vs Semax
Side-by-side of Low-Dose Naltrexone and Semax. 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.
Semax
Semax peptide benefits: nootropic ACTH(4-10) analog without corticotropic activity. Cognitive enhancement, neuroprotection, intranasal dosing, Russian stroke.
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
Semax
- •Synthetic heptapeptide analog of ACTH(4-10) developed in Russia in the 1980s
- •Approved in Russia for ischemic stroke, cognitive impairment, and cerebrovascular disorders
- •Lacks the corticotropic activity of native ACTH due to the Pro-Gly-Pro stabilizing tail
- •Russian RCTs report improved cognitive recovery in acute ischemic stroke versus standard care
- •Modulates BDNF and NGF expression and dopaminergic signaling in preclinical models
- •Standard route is intranasal; not FDA approved; research-use-only outside Russia
Side-by-side
| Attribute | Low-Dose Naltrexone | Semax |
|---|---|---|
| Category | pharmaceutical | peptide |
| Also known as | LDN, naltrexone (low dose) | Met-Glu-His-Phe-Pro-Gly-Pro, ACTH(4-10) Pro-Gly-Pro analog |
| Half-life (hr) ↗ | 4 | 0.5 |
| Typical dose (mg) ↗ | 4.5 | 0.6 |
| Dosing frequency | once daily, typically at bedtime | 2-3x daily (intranasal) |
| Routes | oral | intranasal |
| Onset (hr) | 1 | 0.5 |
| Peak (hr) | 1.5 | 2 |
| Molecular weight | 341.4 | 813.94 |
| Molecular formula | C20H23NO4 | C37H51N9O10S |
| 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. | Modulates BDNF and NGF expression in hippocampus and cortex, enhances dopaminergic and serotonergic signaling, and reduces oxidative stress markers in preclinical ischemia models. Lacks corticotropic activity of native ACTH. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Approved in Russia for stroke and cognitive disorders; not FDA approved; research-use-only grey market elsewhere |
| WADA status | allowed | unknown |
| DEA / Rx | Rx only (not a controlled substance) | Not FDA approved; not scheduled; research-chemical status outside Russia |
| Pregnancy | Insufficient data; not routinely recommended | Not recommended; insufficient data |
| CAS | 16590-41-3 | 80714-61-0 |
| PubChem CID | 5360515 | 9811102 |
| Wikidata | Q426444 | Q4413083 |
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)
Semax
Common side effects
- mild nasal irritation
- transient mild headache
- rare mild euphoria or activation
Contraindications
- pregnancy
- lactation
- acute psychotic disorder
- severe hypertension (caution due to mild activating effect)
Interactions
- stimulants (caffeine, amphetamines): potential additive activation; monitor for overstimulation(minor)
- antipsychotics: theoretical antagonism via dopaminergic modulation(minor)
Which Should You Take?
Low-Dose Naltrexone comes out ahead for most readers on the criteria we weight: 2 catalogued goals, prescription-only, oral dosing, with a Tier-A outcome catalogued. Semax 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 Semax.
- → If your priority is long-term neuroprotection, pick Semax.
Edge case: Half-lives differ materially (Low-Dose Naltrexone ~4 hr vs Semax ~0.5 hr). Low-Dose Naltrexone reaches steady state faster; Semax is easier to dial in if tolerability is uncertain.
Default choice: Low-Dose Naltrexone. Wider use case, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for Semax 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 Semax?
Low-Dose Naltrexone and Semax differ in category (pharmaceutical vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Low-Dose Naltrexone or Semax?
Low-Dose Naltrexone half-life is 4 hours; Semax half-life is 0.5 hours.
Can you stack Low-Dose Naltrexone with Semax?
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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