CognitiveACTH(4-7) Pro-Gly-ProMet-Glu-His-Phe-Pro-Gly-Pro

Semax

Synthetic ACTH(4–10) analog · neuroprotective / nootropic

Semax is a synthetic seven-amino-acid peptide built on a fragment of the natural hormone ACTH, with a stabilizing Pro-Gly-Pro tail added so it resists rapid breakdown. In Russia it is a registered prescription medicine — an intranasal solution used for ischemic stroke and other brain/cognitive indications, and listed among the country's essential medicines. Its best-supported biology is neurotrophic: in rodent brain a single dose raises BDNF and NGF (nerve-growth factors) and activates their TrkB receptor, which is the mechanism most often invoked for its neuroprotective effects. Two honest caveats define this peptide. First, that mechanistic evidence is entirely from animals — there is no human BDNF/receptor data. Second, the clinical evidence is overwhelmingly Russian, often older and small, and has not been independently replicated by Western randomized trials. Semax is not FDA- or EMA-approved, no validated human plasma half-life has been published, and there is no primary-source evidence that it enhances cognition in healthy people.

The short version

Semax is a short synthetic peptide — seven amino acids — based on a piece of the natural stress hormone ACTH. Researchers took the active fragment and added a small tail (Pro-Gly-Pro) so the body's enzymes can't chew it up as fast. The result keeps some of ACTH's signaling effects on the brain while shedding the classic hormonal stress-axis effects.

It is a real, approved medicine — but only in Russia, where it is sold as a nasal spray and used for stroke recovery and certain brain conditions. It is on Russia's list of essential medicines. Outside Russia it has no approval and is sold as a research chemical.

In animal studies, Semax raises levels of brain growth factors (BDNF and NGF) and switches on their receptor — the most likely explanation for the neuroprotective effects reported in Russian stroke research. That growth-factor evidence, though, comes from rats, not people.

Two honest caveats. The human evidence is almost all Russian, often from the 1990s and 2000s, in small studies that Western researchers have not independently repeated. And despite what nootropic marketing claims, there is no solid primary-source study showing Semax makes healthy people smarter, and no reliable published figure for how long it lasts in the body — any specific half-life number you see quoted is unsourced.

Molecular identity

Specs

Molecular weight: 813.9 g/mol
Molecular formula: C₃₇H₅₁N₉O₁₀S
Monoisotopic mass: 813.34796 Da
CAS / UNII: 80714-61-0 · I5FAL2585H
PubChem CID: 9811102

Sequence: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) — 7 AA heptapeptidePubChem CID 9811102
Structure / class: Synthetic ACTH(4-7) fragment (Met-Glu-His-Phe) + C-terminal Pro-Gly-Pro stabilizing tail; neuropeptide / nootropicPubChem CID 9811102; research literature
Water solubility: Freely water-soluble; hydrophilic (computed XLogP −2.8, TPSA 312 Å²)PubChem CID 9811102 (computed properties)
Molecular target: Neurotrophic: upregulates BDNF/NGF and TrkB receptor activation (rodent brain); proposed melanocortin-system activity (unconfirmed). No classic single receptorPMID 16996037 (rodent BDNF/TrkB); melanocortin link proposed only
Half-life: No validated human plasma half-life published; parent peptide rapidly degraded with Pro-Gly-Pro the dominant longer-lived metabolite (rodent)PMID 16523722 (rat intranasal kinetics)
Origin: Synthetic ACTH(4-7) fragment + C-terminal Pro-Gly-ProResearch literature
Regulatory status: Registered prescription drug in Russia (intranasal; on the Russian Vital & Essential Medicines list); not FDA/EMA-approvedRussian drug registry; research literature

Plain English

Mechanism

Semax is a synthetic analog of the ACTH(4–10) region of adrenocorticotropic hormone: it keeps the N-terminal Met-Glu-His-Phe core and replaces the rest with a Pro-Gly-Pro (PGP) tripeptide. That PGP tail is the defining modification — it is itself metabolically stable and biologically active, and it slows the enzymatic degradation that destroys the native ACTH fragment. Importantly, Semax is described as carrying ACTH's neurotrophic signaling WITHOUT driving the classic corticosteroid/stress-axis response of the full hormone.

Its best-characterized mechanism is neurotrophic, and it is established in rodent brain. In rat hippocampus, a single intranasal dose increased BDNF protein, raised exon-III BDNF mRNA, and increased phosphorylation of the TrkB receptor — the pairing (more growth factor plus more active receptor) that drives neuronal survival and plasticity signaling. Radiolabeled Semax showed specific, reversible binding in brain tissue (dissociation constant in the low-nanomolar range) and raised BDNF selectively in the basal forebrain.

Beyond BDNF, Semax shifts the expression of a broader neurotrophin program — NGF and BDNF transcripts change in a region- and time-specific way across hippocampus, frontal cortex, and retina. In a rat model of permanent cerebral ischemia (middle-cerebral-artery occlusion), Semax upregulated BDNF, NGF, and NT-3 together with their high-affinity Trk receptors in the ischemic cortex, which is the molecular rationale for its use in stroke. Every one of these mechanistic findings is from rodents; there is no equivalent human tissue data.

A caution on the receptor question: because Semax derives from ACTH/α-MSH-family sequence, it is sometimes described as acting through melanocortin receptors (MC4R/MC5R). That specific receptor pharmacology is proposed in secondary sources but not firmly established in the primary literature, and should be read as a hypothesis rather than a settled mechanism. The robust, citable picture is the BDNF/NGF/NT-3 + Trk neurotrophic axis above, combined with the absence of the classic endocrine ACTH effects.

Sources:PMID 16996037 PMID 16635254 PMID 17353092 PMID 19633950

Why people reach for it

Potential benefits

Semax is the focus-and-drive end of the Russian nootropic tradition — here's what draws people to it.

Sharper focus and mental drive — Its headline appeal. Semax is described as neurostimulating, raising the brain's dopaminergic and noradrenergic tone — the activation and concentration people reach for when they need to sit down and work or study.
A brain-growth (BDNF) signal — In rodent brain a single dose raises BDNF and NGF (nerve-growth factors) and switches on their TrkB receptor — the neurotrophic pairing people pursue it for, though that mechanism is animal data, not human.
Neuroprotective reputation — Its most-developed clinical use, in Russia, is ischemic-stroke recovery, where it upregulates BDNF, NGF, and NT-3 in the injured cortex — the basis for the neuroprotective profile people associate with it.
Activation without the classic stress response — Semax carries ACTH's neurotrophic signaling but is described as doing so without driving the cortisol/stress-axis effects of the full hormone — drive without the hormonal stress load.
Pairs cleanly with a calm peptide — Because it works on drive rather than calm, it slots alongside Selank — the canonical Russian focus-plus-calm combination.

Sources:PMID 16996037 PMID 17353092 PMID 19633950 PMID 11517472

What people reach for Semax for, drawn from what the research reports (mechanism from animals; clinical use predominantly Russian) and how it's used — not proven outcomes or medical claims.

Implied timing

Best time to dose

Implied best time

Morning to early afternoon

Most people take Semax in the morning or early afternoon, lining the activating effect up with the work or study window and keeping it clear of sleep.

Semax is described as neurostimulating — it raises dopaminergic and noradrenergic tone — so the cognitive and mood effect is wanted during waking hours, when you actually want to be alert and focused.
That same activation is why late dosing is avoided: an afternoon or evening dose can interfere with sleep onset, so the common rule of thumb is to keep it out of the last 4–6 hours before bed.
For the morning-plus-midday split some users run, both doses still land in the first half of the day (e.g. one on waking, one around midday) — the goal is to cover the work window, not the clock as such.
No validated human plasma half-life is published, so the timing is reasoned from the activating mechanism and how people use it, not from a measured duration of action.

No study establishes an ideal time of day for Semax — this is reasoned from its activating mechanism and how it's actually used. As a rule of thumb most peptide dosing lands in the midday-to-evening window; for Semax the lean is the early side of that — morning to early afternoon.

Sources:PMID 16996037 PMID 16523722

How to run it

Dosing & protocol

Semax is intranasal-primary — that is the route of the registered Russian drug, the clinical stroke studies, and the most common community approach. It is also used subcutaneously in the research-peptide context, and the on-page calculator is built for that route. Both are covered below. All ranges and schedules are community-and-practitioner convention extrapolated from the Russian clinical literature and rodent mechanism data — not Western-RCT-validated human dosing.

Community convention, not trial-proven: the clinical evidence is predominantly Russian, older, and small; it has not been replicated by Western randomized trials. Semax is not FDA- or EMA-approved. Every number here is a usage pattern, not established evidence for healthy-person use.

Tiered dose ranges

Intranasal and subcutaneous doses track each other closely in community practice — the difference is delivery route, not magnitude.

Low / entry:: 200–300 mcg/day — first-use tolerance check or a light cognitive-support maintenance dose.
Standard (intranasal):: 300–600 mcg/day — the most-cited community range for nootropic or neuroprotective goals, delivered intranasally; split across two daily doses is common (e.g. 300 mcg AM + 300 mcg midday).
Standard (subcutaneous):: 300–600 mcg/day — same mcg/day magnitude as intranasal; route shifts to subcutaneous injection for users preferring that form.
Acute / clinical reference:: 12–18 mg/day intranasally for 5–10 days — this is the Russian stroke-study regimen, cited for context only; it is not a community nootropic protocol.

Administration — intranasal + subcutaneous

Intranasal is the traditional and most common route; subcutaneous is the research-peptide alternative. Use the route that matches your form.

Intranasal — how to dose:: Reconstituted Semax is administered as nasal drops or with a nasal atomizer. For drops: tilt the head back slightly, instill half the dose per nostril (e.g. for 300 mcg, split evenly across both nostrils), then sniff gently to draw the solution toward the olfactory epithelium rather than down the throat.
Why intranasal works for neuropeptides:: The nose-to-brain route delivers Semax along the olfactory and trigeminal nerve pathways directly toward the brain, partly bypassing the bloodstream and the blood-brain barrier. In rodent studies, intact Semax was measurable in brain tissue within minutes of intranasal dosing. This pathway is why intranasal is the registered clinical route — the peptide reaches the target tissue before systemic degradation clears it.
Subcutaneous — site and rotation:: Injected into subcutaneous fat at the abdomen (a couple of inches clear of the navel), the outer thigh, or the love-handle area. Rotate sites between doses to avoid repeated-use irritation or lipohypertrophy.
Subcutaneous — measuring the dose:: Drawn on a U-100 insulin syringe from the reconstituted vial. At the standard 10 mg vial + 2 mL bacteriostatic water mix (5,000 mcg/mL): 300 mcg = 6 IU · 600 mcg = 12 IU. The on-page calculator adjusts for any vial size.
Time of day:: Morning to early afternoon is the community preference for Semax — see Best time to dose above. It is described as activating (raising dopaminergic and noradrenergic tone), so afternoon or evening dosing can interfere with sleep; avoid dosing within 4–6 hours of sleep.
Food window:: No food interaction is documented for either route. Subcutaneous injection is independent of meals. For intranasal, avoid blowing the nose immediately before or after dosing.

Cycle & washout

Semax is run in defined cycles rather than indefinitely — standard practice for peptides with dopaminergic modulation.

Typical cycle:: 2–4 weeks of daily use is the most common community cycle length. Shorter cycles (1–2 weeks) are used for acute cognitive demands (exam periods, high-output work); longer cycles up to 6 weeks are reported but less common.
Washout:: 1–2 weeks off between cycles, rising to 4 weeks for a longer run. The washout is intended to prevent dopamine-pathway desensitization — tolerance to the energizing/focus effect is the most frequently reported reason to cycle.
Cycle-off indicators:: If the noticeable cognitive effect fades before the cycle ends, that is the practical signal to pause — not a set calendar date.

Reconstitution at a glance

Mixing math only — the calculator does this live. Quick reference for the standard 10 mg vial:

For intranasal use:: 10 mg vial + 2 mL bacteriostatic water = 5,000 mcg/mL (0.5%). Apply as drops with a dropper or via a nasal atomizer. Standard doses: 300 mcg = 0.06 mL (6 drops at 10 mcg/drop if using a standard dropper) · 600 mcg = 0.12 mL. Many users simply use a 1 mL syringe without a needle to measure and drip.
For subcutaneous use:: Same 10 mg + 2 mL mix (5,000 mcg/mL) on a U-100 insulin syringe: 300 mcg = 6 IU · 600 mcg = 12 IU. Alternatively, 10 mg + 4 mL gives 2,500 mcg/mL for a more spread-out syringe scale: 300 mcg = 12 IU.

Sources:PMID 11517472 PMID 10741256 PMID 16523722 PMID 16996037

Substrate the signal needs

Nutritional cofactor precision

Semax's mechanism is neurotrophic (raises BDNF/NGF) plus modulatory (nudges dopamine/serotonin tone). The useful cofactors either supply the raw material those signals run on, amplify the BDNF signal through a proven independent lever, or keep the neurotransmitter substrate topped up. This is reasoned from Semax's biology — not a Semax nutrition study.

Reasoned from Semax's BDNF/NGF + dopaminergic/serotonergic mechanism plus established neuroplasticity nutrition — not a Semax cofactor trial. Supplement doses are established community ranges, not Semax-specific findings.

Supply the substrate — neurotransmitter precursors + membrane DHA

What the dopamine/acetylcholine/serotonin signals Semax nudges are actually built from.

Alpha-GPC or CDP-Choline — 300–600 mg/day:: Choline is the precursor the brain turns into acetylcholine, the attention and memory neurotransmitter. Semax is commonly paired with a choline source in the nootropic community on the logic that raising neurotrophic tone does more when acetylcholine synthesis is well-supplied. Alpha-GPC crosses the blood-brain barrier readily; take in the morning with the first Semax dose.
Omega-3 DHA — 1–2 g/day:: DHA is the dominant structural fat in neuronal cell membranes — it is the physical substrate that BDNF-driven plasticity (new synapses, dendritic growth) builds with. A fish-oil or algae-oil supplement providing ≥1 g DHA daily keeps the membrane pool available for the neuroplasticity Semax's BDNF signal is meant to initiate.
B6 (P5P form) + B9 (methylfolate) + B12 (methylcobalamin) — standard neurological doses:: This methylation trio runs the enzymatic machinery that builds dopamine, serotonin, and norepinephrine from their amino-acid precursors. B6 at 25–50 mg/day, folate at 400–800 mcg/day, and B12 at 500–1,000 mcg/day are the community standard for supporting neurotransmitter synthesis alongside any dopaminergic compound. Take in the morning.

Amplify the BDNF signal — lifestyle levers

BDNF is also raised by exercise and sleep — independently and robustly. Stacking these with Semax is compounding the same mechanism, not adding a new one.

Aerobic exercise — 3–5 sessions/week, 20–40 min:: Sustained aerobic exercise is the best-evidenced way to raise BDNF in humans. Timing it on the same day as Semax dosing is the community approach for compounding the BDNF stimulus — the peptide and the exercise-induced signal work the same receptor (TrkB) through independent pathways.
Sleep quality — 7–9 hours, prioritized:: BDNF synthesis and TrkB receptor sensitivity are tightly linked to slow-wave sleep. Poor sleep effectively undoes the BDNF signal Semax is meant to generate. Sleep hygiene is not optional if the goal is neuroplasticity.

Mitigate — minimal for Semax

Semax has a low side-effect profile in the Russian literature. The one area to watch: overstimulation.

Magnesium glycinate — 200–400 mg in the evening:: Semax's dopaminergic and noradrenergic nudge can show up as evening restlessness or light sleep in some users. Magnesium glycinate in the evening supports NMDA-receptor tone and sleep onset — it is the standard community offset for stimulatory nootropics taken in the first half of the day.

Combinations + timing

Stacking notes + timing windows

Semax drives focus and neurotrophic tone. The best pairings add a complementary lever — calm/anxiolytic balance, or a longer-acting variant swap — not a doubled nootropic signal. The Semax + Selank pair is the canonical Russian nootropic combination.

User combinations reasoned from complementary mechanisms — not regimens studied head-to-head, and Semax's human evidence is mostly Russian clinical data, not Western RCTs, so any stack is doubly unproven. Doses are community convention; 'commonly combined for' describes where users reach, not a proven indication.

Semax + Selank

THE anchor pairing — Semax for focus/neurotrophic drive, Selank for anxiolytic calm. Different levers, not the same one twice.

Why it works:: Semax raises BDNF/NGF and modulates dopamine/norepinephrine — the activation and focus half. Selank is a tuftsin analog developed in Russia as a targeted anxiolytic; it is thought to modulate the GABAergic and serotonin systems, dampening anxiety without sedation. The result is cognitive activation without the edgy or anxiety-prone side that Semax alone can produce in some users — drive and calm from separate mechanisms.
The protocol (intranasal):: Semax 300 mcg intranasally (AM) + Selank 300 mcg intranasally (AM or midday). Both are administered as nasal drops or spray, typically at the same dose time. Some users split: Semax AM for morning drive, Selank midday if afternoon anxiety appears.
The protocol (subcutaneous alternative):: Semax 300–600 mcg SC once daily + Selank 300–600 mcg SC once daily, both in the morning or one AM / one midday.
Outcome:: The combination users commonly reach for on cognitive-performance, high-output work, and anxious-focus goals. Both peptides share the Russian-clinical evidence profile — limited Western replication applies to the stack as well as to either compound alone.

Semax + Alpha-GPC (nootropic foundation layer)

Pairing Semax with a choline source rather than another peptide — supplying the acetylcholine substrate the cognitive effect draws on.

Why it works:: Alpha-GPC provides choline, the raw material for acetylcholine synthesis — the neurotransmitter central to attention, working memory, and the cholinergic side of cognition. Semax's neurotrophic and dopaminergic action runs in parallel with the cholinergic system, not through it; the two compounds supply different parts of the cognitive machinery rather than the same signal twice.
The protocol:: Semax 300–600 mcg (intranasal or SC, AM) + Alpha-GPC 300–600 mg taken orally 30 minutes before the first Semax dose or simultaneously. This is the most common non-peptide pairing in the Semax community.
Outcome:: Commonly combined for sustained focus and working-memory support during cognitively demanding periods — effectively a peptide + choline stack as a functional alternative to racetam/choline combinations.

Reconstitution math

Reconstitution calculator

Calculated for a 1 mL U-100 insulin syringe (100 units/mL).

Peptide per vial

BAC water added

Desired dose

Units per dose

Draw to this mark on a U-100 syringe

Volume per dose: 0.06 mL
Doses per vial: 33
Concentration: 5 mg/mL

One vial lasts

Daily: 33 days
Every other day: 66 days
5×/week: 46 days

Research use only. Not for human consumption. Outputs are reference values based on research literature — verify all measurements independently.

From the studies

Side effects from research

Russian clinical reports describe intranasal Semax as generally well-tolerated, and the optic-nerve study specifically noted no negative structural effect on the optic nerve head. That tolerability picture, however, comes from small Russian studies — there is no large, independent (non-Russian) safety database and no long-term controlled safety surveillance.

Semax is not an FDA- or EMA-approved medicine; outside Russia it is sold as a research chemical. Anyone weighing it should understand that the favorable safety impression rests on limited domestic data rather than the kind of long-term safety monitoring required for drug approval in the US or EU. This page presents the research literature only and makes no therapeutic claims.

Sources:PMID 10741256

As reported in literature

Research dosing ranges

This table is the research and registration evidence the practical figures above lean on — shown separately so study data is never mistaken for a personal dosing recommendation, and this page makes no therapeutic or how-to claim. Two cautions frame it. First, the human doses come from Russian clinical studies that are small and, by modern standards, methodologically limited (not randomized or blinded by today's trial standards); they are not Western-RCT-validated. Second, the rodent doses (in µg/kg — micrograms per kilogram of body weight) are mechanism experiments in animals and do not translate to a human dose. The widely circulated "600–1,200 mcg/day for cognitive enhancement" figure has no clinical-trial source and is omitted as anecdotal.

Dose	Route	Model	Outcome	Sources:
12 mg/day (moderate), 18 mg/day (severe); 5–10 day course	Intranasal	Human — acute hemispheric ischemic stroke (n≈30 vs 80 controls)	Reported accelerated regression of cerebral and focal (especially motor) deficits; non-randomized, Russian-language	PMID 11517472
Intranasal 0.1% / 1% solution	Intranasal	Human — registered Russian drug (stroke, cognitive, optic-nerve indications)	Marketed formulation strengths; 0.1% for milder indications, 1% for stroke/optic-nerve per Russian labeling	PMID 10741256
Endonasal / drops	Intranasal	Human — optic nerve disease (controlled, 3-group)	Reported improved visual acuity, visual-field extension, and optic-nerve electrical sensitivity; small, Russian-language	PMID 10741256
50 µg/kg, single dose	Intranasal	Rat — hippocampus (mechanism)	Increased BDNF protein, BDNF mRNA, and TrkB phosphorylation; improved conditioned-avoidance behavior	PMID 16996037
Repeated dosing	Intranasal	Rat — permanent MCAO ischemia (mechanism)	Upregulated BDNF, NGF, NT-3 and their Trk receptors in ischemic cortex	PMID 19633950

Quick answers

Frequently asked

What is Semax?

Semax is a synthetic seven-amino-acid peptide (Met-Glu-His-Phe-Pro-Gly-Pro) based on the ACTH(4-7) fragment of adrenocorticotropic hormone, with a Pro-Gly-Pro tail added for stability. In Russia it is a registered intranasal medicine used for ischemic stroke and brain/cognitive indications; outside Russia it is not approved and is sold as a research chemical.

How does Semax work?

Its best-supported mechanism is neurotrophic and comes from rodent studies: a dose raises brain growth factors BDNF and NGF and activates their TrkB receptor, which supports neuronal survival and plasticity. It appears to do this without triggering the classic stress-hormone (corticosteroid) effects of full ACTH. All of this mechanistic evidence is from animals — there is no human tissue data.

Is the evidence for Semax strong?

It is mixed and must be read honestly. The chemistry and identity are solid, and the rodent neurotrophic mechanism is well-documented. But the clinical efficacy evidence is overwhelmingly Russian, often from the 1990s–2000s, in small and frequently non-randomized studies, and it has not been independently replicated by Western randomized controlled trials.

Does Semax improve cognition in healthy people?

There is no primary-source clinical trial showing that Semax enhances cognition in healthy adults. The much-repeated description of a study in '30 healthy adults' improving attention or memory has no traceable citation and appears to originate from nootropic marketing, not the scientific literature.

What is Semax's half-life?

No validated human plasma half-life has been published. In rodents the parent peptide is degraded rapidly, while its Pro-Gly-Pro metabolite is comparatively stable, and the biological effects outlast the peptide itself. The specific half-life numbers quoted online are mutually contradictory and not traceable to a primary pharmacokinetic study.

Is Semax approved or banned in sport?

It is a registered prescription drug in Russia but is not FDA- or EMA-approved. It is not specifically named on the WADA Prohibited List, but because it lacks approval by major regulators it may fall under WADA's S0 'non-approved substances' clause — athletes should treat it as potentially prohibited. The specific WADA classification is not independently confirmed here.

What is NA-Semax-Amidate and how does it differ from Semax?

NA-Semax-Amidate (N-acetyl Semax amidate) is a modified form of Semax with added N-acetyl and C-amide groups intended to improve enzymatic stability. It is sometimes described as more potent or longer-acting than Semax, but those specific pharmacokinetic claims are vendor-originated and not published in peer-reviewed literature. It is a different molecule (PubChem CID 172638603) — not interchangeable with Semax proper.

Primary sources

References

PubChem CID 9811102PubChem CID 9811102 (Semax / ACTH(4-7) Pro-Gly-Pro)
PMID 16996037Dolotov et al., Brain Res 2006 (Semax raises BDNF protein/mRNA and TrkB phosphorylation, rat hippocampus)
PMID 16635254Dolotov et al., J Neurochem 2006 (specific brain binding KD ≈ 2.4 nM; basal-forebrain BDNF, rat)
PMID 17353092Agapova et al., Neurosci Lett 2007 (region-specific NGF/BDNF transcript changes, rat brain)
PMID 19633950Dmitrieva et al., Cell Mol Neurobiol 2009 (Semax & PGP upregulate BDNF/NGF/NT-3 + Trk receptors after cerebral ischemia, MCAO rat)
PMID 16523722Shevchenko et al., Bioorg Khim 2006 (intranasal brain penetration & rapid degradation; PGP dominant metabolite, rat)
PMID 11517472Gusev, Skvortsova, Miasoedov et al., Zh Nevrol Psikhiatr 1997 (Semax in acute ischemic stroke; 12/18 mg/day intranasal)
PMID 10741256Polunin et al., Vestn Oftalmol 2000 (Semax in optic nerve disease; controlled 3-group study)

Research use only · Not medical advice · Updated 2026-06-01