Cognition and MoodWell researchednootropicneuroprotectionBDNFfocusRussian

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.

Reviewed by the amino101 editorial team. , first published .

Status
Prescription drug in Russia, not FDA approved
Typical dose
200 to 600 mcg
one to three times daily
Route
Intranasal, Subcutaneous
Intranasal, split across both nostrils; subcutaneous is an alternative for people who get nasal irritation
Cycle
10 to 20 days
Break: a break of similar length, 10 to 20 days
Storage
Fridge 2 to 8 C
fridge 2 to 8 C once mixed or as a nasal spray, use within 4 weeks; lyophilized in fridge or freezer away from light

Quick start

What people commonly do. Not a prescription.
Typical dose
200 to 600 mcg
How often
one to three times daily
Where
Intranasal, split across both nostrils; subcutaneous is an alternative for people who get nasal irritation
Timing
morning or early afternoon; late doses can disturb sleep; food does not matter
Effects timeline
alertness within 15 to 30 minutes of a dose; steadier focus and mood over 1 to 2 weeks
Storage
fridge 2 to 8 C once mixed or as a nasal spray, use within 4 weeks; lyophilized in fridge or freezer away from light
Cycle length
10 to 20 days
Break between
a break of similar length, 10 to 20 days

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.

Molecular weight
813.9 Da
Length
7 amino acids
Type
Heptapeptide (ACTH 4-10 analog)
Sequence
Met-Glu-His-Phe-Pro-Gly-Pro

Where the research stands

Human trials
Small pilots only
Animal data
Extensive
Safety data
Limited
Regulatory
Approved in Russia only, as a prescription nasal solution; not approved by the FDA or EMA
WADA
Not listed
Recovery after ischemic strokeModerate evidence
  • Neurological recovery in the first days after stroke. Russian multicenter clinical experience with the 1 percent solution reports faster recovery, but the studies are not blinded to Western standards.
  • Gene expression after ischemia. In a rat stroke model, Semax shifted hundreds of immune and vascular genes toward a repair profile.
Attention, memory, and cognitive complaintsModerate evidence
  • Attention and memory tasks in healthy volunteers. Small Russian pilot studies found improved performance after a single nasal dose.
  • Cognitive complaints and asthenia. The registered 0.1 percent indication in Russia rests on open-label and small controlled studies.
  • BDNF and TrkB in the hippocampus. Rodent studies show increases within hours of nasal dosing, which is the mechanistic basis for the cognitive claims.
Optic nerve diseaseEmerging
  • Optic nerve atrophy and glaucoma. Russian clinical reports describe improved visual function, with no independent replication.
Anxiety and painWeak or mixed
  • Anxiety-like behavior and pain response. Rodent only; Semax reduced both without raising corticosterone, but nothing comparable has been shown in people.
Key findings
  • 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.

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.

Levels over time

Modeled from the half-life. Illustrative, not measured.
Peak
within 15 to 30 minutes of a nasal dose, judging by reported onset; uptake to the brain along olfactory pathways is fast
Half-life
a few minutes in blood
Cleared
under an hour from plasma; gene expression changes such as BDNF induction persist for many hours
Repeated dosing every 24 hDose
100%50%dose 114m27m41m54mnext dose at 24h, long after clearance
What this means for dosing

A half-life of 6 min against dosing every 24 h means each dose has cleared before the next. Nothing stacks; you start from zero every time, and the tissue effect is what carries over.

Blood levels tell you little here; the peptide is gone within minutes but the downstream neurotrophin effects last hours to days, which is why short courses of one to three doses a day are used rather than anything continuous.

Semax dosage and protocols

Courses of 10 to 20 days followed by a break of similar length. No loading or taper; most start at the low end once daily and add a second dose if needed. Some tolerance to the alerting effect is reported with continuous daily use, which is one reason for the breaks.

GoalDoseFrequencyRoute
Daily focus200 to 300 mcgonce or twice dailyIntranasal
Cognitive complaints, full course300 to 600 mcgtwo to three times dailyIntranasal
Injected alternative200 to 400 mcgonce dailySubcutaneous
As needed before demanding work200 mcgsingle doseIntranasal
Timing

Morning and early afternoon; avoid dosing after mid afternoon. Nasal use does not depend on food. Often paired with Selank in the same day, Semax earlier for drive and Selank later for calm.

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

Dose calculator

U-100 insulin syringe
Draw
- units
- mL at -
- doses per vial. - per unit.

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.

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

How to reconstitute Semax

  1. 1

    Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.

  2. 2

    Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.

  3. 3

    Draw the bacteriostatic water into a mixing syringe.

  4. 4

    Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.

  5. 5

    Swirl gently or leave it to dissolve. Do not shake.

  6. 6

    Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.

  7. 7

    Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.

  8. Full walkthrough with syringe reading and site rotation: reconstitution guide.
Quality check
  • ✓
    White, fluffy cake

    Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.

  • ✓
    Clear after mixing

    Once dissolved the solution should be water-clear with nothing floating in it.

  • !
    Slight clumping

    Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.

  • ✕
    Collapsed or melted

    Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.

  • ✕
    Cloudy or particles

    Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.

What to expect
  1. Day 1 to 3

    Alertness within half an hour of a nasal dose, sometimes with restlessness or a mild edge; nasal dryness starts.

  2. Week 1 to 2

    Steadier focus and mental stamina, often a mood lift; this is where most people decide whether it works for them.

  3. Week 2 to 3

    Effects plateau and the initial buzz may fade; the course ends here.

  4. After the course

    Effects taper over 1 to 2 weeks with no reported withdrawal; the break lets tolerance reset.

Interactions and stacking

Selanksynergistic

Developed by the same lab and often used together; Selank covers anxiety while Semax covers focus.

Pinealoncompatible

Used as a low-intensity background bioregulator during Semax courses; no combined data.

DSIPcompatible

Opposite ends of the day, Semax in the morning and DSIP at night, with no known overlap.

Stimulants (caffeine, ADHD medications)caution

Additive restlessness, irritability, and insomnia; keep caffeine moderate on Semax days.

SSRIs and other serotonergic drugscaution

Rodent data show Semax alters serotonin and dopamine turnover; no human interaction data exists.

Alcoholcaution

Undermines the cognitive effect and worsens next day irritability; no specific interaction known.

Safety

Side effects and cautions
  • ▲Nasal irritation, dryness, and occasional nosebleeds
  • ▲Restlessness or irritability, mainly at higher doses
  • ▲Trouble sleeping when dosed late in the day
  • ▲Occasional headache
  • ▲Hair thinning reported anecdotally by a minority of long-term users
  • ▲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.
Stop and reassess if
  • ■Nosebleeds or nasal pain persist
  • ■Insomnia does not resolve after moving doses earlier
  • ■Anxiety or irritability gets worse rather than better
  • ■You notice hair shedding
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.

Community poll

Self-reported by visitors. Not clinical evidence.
What is your experience with Semax?
If you have used it, how well did it work for you?
Any side effects?
Where did you first hear about it?

Semax: 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