Semax
Methionyl-glutamyl-histidyl-phenylalanyl-prolyl-glycyl-proline · MEHFPGP · ACTH(4-7)-Pro-Gly-Pro · Semax 0.1%
Russian ACTH-fragment peptide dosed intranasally for focus, drive and neuroprotection.
Typical dose
300 mcg
Once daily, occasionally split AM and early afternoon
Range
200–600
mcg
Half-life
—
see Dosing
Evidence
Early human
Intranasal · Subcutaneous
What it is
Semax is a synthetic heptapeptide made from the ACTH(4-7) behavioural fragment with a Pro-Gly-Pro tail added to resist enzymatic breakdown. Same lab and same design logic as Selank — the Ashmarin/Myasoedov group at the Institute of Molecular Genetics in Moscow — but the parent fragment is the part of ACTH responsible for attention and learning effects rather than the immune-active tuftsin.
Critically, it has no corticotropic activity. The fragment was chosen precisely because it keeps the behavioural effects of ACTH without driving cortisol release, so it does not act like an adrenal stimulant.
It is a registered pharmaceutical in Russia in two strengths: 0.1% nasal drops for cognitive complaints and asthenia, and 1% drops for acute ischaemic stroke and optic nerve atrophy. Stroke protocols use 12-18 mg per day — an order of magnitude above anything used recreationally — under hospital supervision.
Subjectively most people describe clean focus and verbal fluency with more drive than a stimulant gives, and none of the sympathetic load. It is stimulating enough to wreck sleep if taken late.
How it works
The best-supported mechanism is upregulation of BDNF and NGF along with their receptors in the hippocampus and cortex — this has been shown repeatedly in rodents at nootropic-range doses, with changes in gene expression appearing within hours of a single intranasal dose. Semax also binds in the basal forebrain and raises BDNF protein there specifically.
Secondary actions include inhibition of enkephalin-degrading enzymes (shared with Selank), modulation of dopaminergic and serotonergic turnover, and anti-inflammatory effects on brain tissue after ischaemia. The neuroprotective stroke data is thought to run through the inflammatory and neurotrophic arms rather than any direct vascular effect.
Dosing
Russian acute-stroke protocols run 12-18 mg/day intranasally in hospital — do not extrapolate from those numbers. Higher is not better for cognitive use; overshooting typically produces irritability and anxiety rather than more focus.
Reconstitution calculator
Pre-loaded with Semax’s vial size, water volume and typical dose. Change anything.
Typical: 300 mcg · range 200–600
Draw to
12 u
0.12 mL · 300 mcg
Concentration
2.5 mg/mL
25 mcg per unit
Doses per vial
16.7
Vial lasts
2 weeks 3 days
Draw to 12 units on the barrel.
Once mixed
Refrigerated at 2-8 °C, used within 3-4 weeks. Keep the working nasal bottle in the fridge between doses rather than leaving it out.
2 mL of bacteriostatic water into a 5 mg vial gives 2,500 mcg/mL, so a 300 mcg dose is 0.12 mL. Aim the water down the vial wall and swirl rather than shaking. If you decant into a nasal spray bottle, confirm the per-actuation volume — most metered pumps deliver 0.05-0.1 mL, which is 125-250 mcg at this concentration.
Storage
Before mixing
Freezer at -20 °C for 24+ months; stable refrigerated for months and tolerates ambient shipping.
After mixing
Refrigerated at 2-8 °C, used within 3-4 weeks. Keep the working nasal bottle in the fridge between doses rather than leaving it out.
Reported benefits
- ▪Clean improvement in focus, verbal fluency and task persistence
- ▪Raises BDNF and NGF expression in cortex and hippocampus in animal work
- ▪Motivating without the sympathetic load, appetite loss or crash of a stimulant
- ▪Human stroke and cerebrovascular trial data supporting a neuroprotective effect
- ▪No corticotropic activity despite being an ACTH fragment — does not raise cortisol
- ▪Also used in Russia for optic nerve conditions, with a plausible retinal neurotrophic basis
Side effects
- ▪Nasal burning and irritation, worse with concentrated homemade solutions
- ▪Insomnia if dosed too late in the day
- ▪Irritability, restlessness or anxiety at higher doses
- ▪Headache, usually in the first few days
- ▪Emotional blunting or apathy reported by a minority on longer runs
- ▪No controlled long-term human safety data beyond short clinical courses
Do not use if
- ▪Pregnancy and breastfeeding — no data
- ▪Bipolar disorder or psychotic illness, where a stimulating agent can destabilise
- ▪Acute anxiety disorders, which it can worsen rather than help
- ▪Stacking on top of high-dose stimulants, which compounds the restlessness
Evidence level — Early human
Small or early-phase human studies only.
Registered as a prescription intranasal drug in Russia; not FDA-approved and sold elsewhere as a research chemical.
Commonly run with
Semax FAQ
What is the difference between Semax and N-Acetyl Semax Amidate?+
NA-Semax is a modified version with an acetylated N-terminus and amidated C-terminus, sold as being more stable and more potent by weight. It is a distinct molecule with almost no published data, so Semax dosing does not carry over directly — people typically use lower microgram amounts and titrate.
Does it raise cortisol, being an ACTH fragment?+
No. The 4-7 fragment was specifically chosen because it carries the behavioural effects of ACTH without the corticotropic sequence. This is well established and is the main reason it was developed rather than using ACTH itself.
Can I inject it instead of using it nasally?+
Subcutaneous injection works, but every registered protocol and essentially all of the clinical evidence uses intranasal delivery, which puts peptide into the CNS with less systemic degradation. Injecting adds nothing except more sting and more waste.
How does it compare to Selank?+
Semax pushes focus and drive up; Selank pulls anxiety down. They are commonly run together for that reason — Semax in the morning, Selank later if the day gets stressful. Semax is the one that will keep you awake.
How strong is the human evidence really?+
Better than most nootropic peptides but still weak by Western standards. The stroke and cerebrovascular trials are Russian, mostly published in Russian-language journals, and rarely meet modern blinding and reporting standards. The rodent BDNF work is more consistent and comes from multiple groups.
References
- 1.Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus — Brain Research (2006) PMID 16996037
- 2.Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain — Journal of Neurochemistry (2006) PMID 16635254
- 3.The efficacy of semax in the treatment of patients at different stages of ischemic stroke — Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova (2018) PMID 29798983
- 4.Functional Connectomic Approach to Studying Selank and Semax Effects — Doklady Biological Sciences (2020) PMID 32342318
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