Cognition and MoodnootropicneuroprotectionBDNFfocusRussian

Semax

Also known as Met-Glu-His-Phe-Pro-Gly-Pro, ACTH(4-10) analog, NA-Semax, N-Acetyl Semax

Semax is a seven-amino-acid peptide based on a fragment of ACTH, developed in Russia as a nasal drug for stroke recovery and cognitive impairment. People use it for focus, mental stamina, and mood support.

Status
Prescription drug in Russia, not FDA approved
Reported dose
200 to 600 mcg
Intranasal is the standard route. Subcutaneous users typically stay in the same range. Russian 0.1 percent drops deliver roughly 50 mcg per drop.
Frequency
One to three times daily
10-20 days on, then a break of similar length is the common pattern
Route
Intranasal, Subcutaneous
Half-life
A few minutes in blood, but effects on gene expression last many hours

Overview

Semax is a synthetic heptapeptide built from the 4-10 fragment of adrenocorticotropic hormone (ACTH), with the last two residues swapped for Pro-Gly-Pro to make it more stable in the body. It was created at the Institute of Molecular Genetics in Moscow in the 1980s and 1990s and has been an approved medicine in Russia since the mid 1990s, sold as a 0.1 percent nasal solution for cognitive complaints and a 1 percent solution for acute ischemic stroke. Unlike ACTH itself, Semax does not stimulate cortisol release, which is the whole point of the modification.

The Russian clinical literature is fairly large but mostly consists of open-label or small controlled studies published in Russian-language journals. Those report faster recovery after stroke, improved attention in healthy volunteers and in people with attention problems, and benefit in optic nerve disease. The methodology is generally weaker than what Western regulators expect, and there are essentially no large, independent, double-blind trials from outside Russia. That is the honest state of the human evidence.

Animal and cell work is more consistent. In rodents, Semax increases BDNF and its TrkB receptor in the hippocampus, protects neurons during ischemia, dampens inflammatory gene expression after stroke, and has mild anxiolytic and analgesic effects. Whether the doses people use at home reproduce those changes is not known. The community version comes as lyophilized powder for nasal or subcutaneous use, or as ready-made nasal sprays, sometimes in an N-acetyl form marketed as longer acting.

How it works

Semax is thought to act mostly through neurotrophin signaling. Within hours of administration it raises BDNF expression in the hippocampus and frontal cortex and increases TrkB receptor levels, which supports synaptic plasticity and neuronal survival. It also modulates the melanocortin system without the corticotropic effect of the parent hormone, and rodent gene expression studies show it shifting immune and vascular gene activity after ischemia toward a repair profile. Additional reported actions include reduced enkephalin breakdown, influence on serotonin and dopamine turnover, and antioxidant effects. Nasal delivery is favored because the peptide reaches the brain quickly along olfactory pathways and is degraded fast in blood.

What the research shows

  • rodentNasal Semax increased BDNF protein and TrkB receptor levels in rat hippocampus within hours of dosing.
  • rodentIn a rat stroke model, Semax shifted expression of hundreds of genes involved in immune response and vascular repair after ischemia.
  • human pilotRussian clinical studies report faster neurological recovery when 1 percent Semax is given during the first days after ischemic stroke.
  • human pilotHealthy volunteers showed improved attention and memory task performance after a single nasal dose in small Russian studies.
  • rodentSemax reduced anxiety-like behavior and pain response in rodents without raising corticosterone.

Evidence labels: rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.

Dose calculator

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Draw
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Units are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.

Dosing and protocol

Reported range
200 to 600 mcg per dose

Intranasal is the standard route. Subcutaneous users typically stay in the same range. Russian 0.1 percent drops deliver roughly 50 mcg per drop.

Frequency
One to three times daily

10-20 days on, then a break of similar length is the common pattern

Timing

Morning or early afternoon. Late doses can interfere with sleep for some people.

Common vial sizes and reconstitution
VialSuggested waterConcentrationLow dose draw
5 mg2 mL2.5 mg/mL8 units
10 mg2 mL5 mg/mL4 units
Storage

Lyophilized: fridge or freezer, away from light. Reconstituted or nasal spray: fridge 2-8C, use within 4 weeks. Peptide nasal solutions degrade faster once opened.

Cautions

  • Nasal irritation, dryness, and occasional nosebleeds with frequent use.
  • Some people report restlessness, irritability, or trouble sleeping, especially at higher doses or late in the day.
  • Hair thinning is reported anecdotally by a minority of long-term users, though it has not been studied.
  • Almost all human data comes from Russian studies with limited independent replication.
  • Ready-made nasal sprays lose potency quickly if stored warm, so cheap sprays of unknown age may be nearly inert.

Commonly stacked with

Frequently asked

Does Semax raise cortisol like ACTH does?

No. The 4-10 fragment does not activate the adrenal cortex, which is why Semax was designed from that region of the hormone. Rodent studies confirm no corticosterone rise, and it is used clinically in Russia without adrenal side effects.

Is intranasal or injectable better?

Intranasal is how it was developed and studied, and it gets the peptide to the brain efficiently. Some people inject it subcutaneously to avoid nasal irritation. There is no head-to-head human data, so route is mostly a matter of preference and tolerance.

What is NA-Semax or N-Acetyl Semax?

It is Semax with an acetyl group on the N-terminus, marketed as more resistant to enzymes and longer lasting. Vendors claim stronger effects, but there is very little published research specifically on the acetylated version, so those claims are mostly extrapolation.

How fast does it work?

Effects on alertness are often reported within 15 to 30 minutes of a nasal dose. Changes in BDNF-related plasticity in animal studies build over hours to days, which is why courses of a couple of weeks are typical.

References

  1. Semax, an analog of ACTH(4-10), induces BDNF expression and increases TrkB levels in rat hippocampus. Brain Research, 2006
  2. Semax treatment alters expression of immune and vascular genes in rat brain after focal ischemia. BMC Genomics, 2013
  3. Semax, an analogue of ACTH(4-10) with cognitive effects: clinical and experimental studies (review). Neuroscience and Behavioral Physiology, 1997
  4. Use of Semax in acute ischemic stroke: Russian multicenter clinical experience. Zhurnal Nevrologii i Psikhiatrii, 2005
Educational only. Dose ranges describe what appears in published research and community protocols. This is not medical advice and most of these compounds are not approved for human use. Talk to a clinician who knows your history.