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Semax

Also known as ACTH(4-7)-PGP, (Pro8,Gly9,Pro10)ACTH-(4-10), MEHFPGP

Russian-registered heptapeptide derived from ACTH, studied in stroke and cognitive complaints.

early-clinical Neuro & cognition approved drug

At a glance

Category
Neuro & cognition
Status
approved drug
Route
intranasal (registered dosage form: nasal drops); in research and on the grey market also subcutaneous or intravenous
Half-life
Short (order of minutes) due to peptidase degradation; exact human pharmacokinetics have not been documented in accessible peer-reviewed literature
Onset
minutes to hours for acute effects; cognitive claims are assessed over courses of 3-14 days
Molecular weight
813.9 g/mol
Sequence
Met-Glu-His-Phe-Pro-Gly-Pro

Registered in Russia and nowhere else. The Russian prescribing information describes Semax as nasal drops in two strengths, 0.1% and 1%, with separate indications for each 89. That registration is a real regulatory fact, and it is a fact about Russia only: it says which authority approved the product, not how strong the evidence behind it is - see the evidence section, which is thin and almost entirely Russian-language. The claim that Semax appears on the Russian list of vital and essential medicines (ZhNVLP) is repeated widely but the government list itself was not opened for this entry and is left uncited. Not assessed or approved by the EMA or the FDA; in the EU and the US it is sold exclusively as a 'research chemical'.

Doping status: Not listed by name; on the usual reading it falls under the residual category S0

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Semax is a synthetic analogue of the ACTH(4-7) fragment (Met-Glu-His-Phe), extended with Pro-Gly-Pro at the C-terminus. That extension makes the molecule resistant to peptidases. The commonly used description 'ACTH(4-10) analogue' is inaccurate: residues 8-10 of native ACTH (Arg-Trp-Gly) have in fact been replaced.

The best-supported action is upregulation of neurotrophins. In animal models, Semax and the metabolite Pro-Gly-Pro increase the transcription of BDNF, NGF and their receptors, particularly after cerebral ischaemia 3. In a Russian clinical study, a rise in plasma BDNF was measured in treated patients 5; that is the strongest mechanistic datum in humans.

Genome-wide transcriptional analyses in rat models of focal ischaemia show changes in immune- and vascular-related gene expression 4. This has been found consistently by a limited number of research groups.

Additional proposed mechanisms - antagonism or partial agonism at melanocortin receptors, inhibition of enkephalin degradation, and activation of dopaminergic and serotonergic systems - are largely hypotheses derived from the design principle of the compound. Semax in fact lacks the Arg-Trp motif that is decisive for melanocortin receptor binding, and the reported inhibition of enkephalin degradation is pharmacologically weak. The precise mechanism of action has not been elucidated.

What the research shows

Semax is registered in Russia on the basis of research that does not meet Western standards: small, almost exclusively Russian-language studies from a limited circle of researchers around the developing institute, mostly without blinding and without a placebo group. There is not a single multicentre, independently replicated RCT and no Cochrane assessment. The Russian registration therefore says little about the strength of the evidence.

Research in humans

The human literature consists of a few dozen studies, most of which appeared in a single Russian journal (Zh Nevrol Psikhiatr Im S S Korsakova). Examples: research into acute ischaemic stroke from 1997 and 1999 12, and a 2018 study in 110 patients at different stages of stroke with 6000 mcg per day in two courses of ten days, reporting improvement on the Barthel index and a rise in BDNF - without any described blinding or placebo arm 5. Methodologically the strongest is a randomised, placebo-controlled fMRI study in 52 healthy participants (2020), which showed altered functional connectivity 5 and 20 minutes after administration 6; that, however, is a biomarker study, not an outcome study. Frequently quoted precise effect percentages in stroke (for instance a particular percentage of NIHSS improvement) cannot be traced to an indexed publication and have deliberately been omitted here.

Animal and lab research

The overwhelming majority of the literature is preclinical: rat models of focal ischaemia, transcriptomic and proteomic analyses, and behavioural studies. These studies consistently support a neurotrophic and anti-inflammatory profile after ischaemia, but were done in acute lesion models that translate poorly to cognitive enhancement in healthy people.

Caveats. Main caveats: almost all clinical studies come from the same research groups, with the developer of the compound as a recurring co-author; sample sizes of about 50-110 participants; blinding and placebo control are absent or not reported; publication in a single Russian-language journal with limited external scrutiny; no replication outside Russia. There are no published human pharmacokinetic data and no long-term safety data.

What it is used for

  • Registered in Russia for intellectual-mnestic disorders in vascular brain disease, states following traumatic brain injury, neurosurgery and anaesthesia, discirculatory encephalopathy, stress adaptation, optic nerve atrophy, and minimal brain dysfunction in children from 5 years (0.1%) 8
  • Registered in Russia for acute ischaemic stroke and related acute conditions (1%) 9
  • Outside Russia mainly used as a self-administered nootropic for concentration and mental fatigue - an application that has no clinical support

Dosing

Dose
There is no single Semax dose; the figure depends on which of the two registered strengths is meant, and they are not interchangeable. Semax 0.1% nasal drops (1 mg/ml, 50 mcg per drop), for the cognitive and cerebrovascular indications: 500-5000 mcg per day. Semax 1% nasal drops (10 mg/ml, 500 mcg per drop), registered for acute ischaemic stroke only: 6000-12000 mcg per day in moderate stroke and 12000-20000 mcg per day in severe stroke. Grey-market nootropic use circulates 300-1000 mcg per day intranasally, which corresponds to no registered indication.
Frequency
0.1%, per the Russian label: single dose 200-2000 mcg (3-30 mcg/kg) given as 2-3 drops per nostril, repeated during the day to reach the daily total. 1%, acute ischaemic stroke only: 2-3 drops per nostril (2000-3000 mcg) 3-4 times daily at 3-4 hour intervals in moderate stroke, and 3-4 drops per nostril (3000-4000 mcg) 4-5 times daily at 2.5-3 hour intervals in severe stroke.
Route
intranasal; the drops are administered in both nostrils
Duration
0.1%: 3-5 days, extended to 14 days if needed; 7-10 days for the optic nerve indications; 30 days in children aged 5 and over. 1%: 10 days. User protocols use 10-14 days with breaks.
  • The nootropic figure and the stroke figure are separate things. The 0.1% product at 500-5000 mcg per day covers the cognitive and cerebrovascular indications 8; the 1% product at 6000-20000 mcg per day is registered for acute ischaemic stroke and nothing else 9. A stroke dose is not a large nootropic dose - it is a different product, for a different condition, given in hospital.
  • The Russian label for 0.1% expresses the dose per kilogram (3-30 mcg/kg single, 7-70 mcg/kg daily), not as a fixed amount 8. Figures quoted as absolutes lose that.
  • The 2018 study often cited for '6000 mcg per day' was not an acute-stroke study: it treated 110 patients in the early and late rehabilitation periods, around 3 and 7 months after stroke, with two 10-day courses separated by 20 days. That regimen is neither the acute 1% label schedule nor a nootropic one.
  • One drop is 0.05 ml from either bottle, so an identical number of drops delivers ten times more peptide from the 1% bottle than from the 0.1% bottle. Secondary sources regularly confuse the two, which is how incorrect microgram figures circulate.
  • Doses for use outside the registered indications come from user protocols and sales sites, not from validated clinical research.
  • Grey-market subcutaneous and intravenous use is not covered by any of these figures. The registered doses are intranasal, and a nasal microgram figure cannot be carried across to an injected one - no pharmacokinetic work connects them.
  • There is no dose-response research in healthy people.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Intranasal nootropic course (grey market)

user protocol — not validated

Source: user protocols and vendor material

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Daily, 10-14 days300-1000 mcg per day in total, as nasal drops divided between both nostrils
Thena break of comparable length before any repeat course

This is a nasal-drop schedule and is not interchangeable with any injected one; no pharmacokinetic work connects the two routes. The microgram figure depends entirely on the strength in the bottle: 0.1% delivers 50 mcg per drop and 1% delivers 500 mcg from the same 0.05 ml drop, and secondary sources routinely confuse the two. Nothing here is a stroke schedule. The registered 0.1% product is dosed at 500-5000 mcg per day for 3-14 days for cognitive and cerebrovascular indications, and the registered 1% product is dosed at 6000-20000 mcg per day for 10 days for acute ischaemic stroke alone - a hospital treatment for an emergency, not a larger version of this course.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes
3 ml vial of nasal drops (registered product), 5 mg, 10 mg, 30 mg (lyophilised powder, research chemical)
Solvent
bacteriostatic water (0.9% benzyl alcohol); the registered product is a ready-to-use solution and does not need to be dissolved
Storage
Registered product: store below 10 °C, do not freeze, protect from light; shelf life 2 years. Lyophilised powder: -20 °C, reconstituted 2-8 °C and according to suppliers stable for about 3-4 weeks - these are not pharmacopoeia data.

Worked example

10 mg vial + 2 ml bacteriostatic water = 5 mg/ml. For intranasal use the solution is transferred into a nasal spray bottle; 100 mcg then corresponds to 0.02 ml.

Let the water run down the wall of the vial, swirl gently, do not shake. The N-terminal methionine is susceptible to oxidation; protection from light and heat is therefore relevant. Avoid repeated freezing and thawing.

This is administered as nasal drops or spray, not by injection, so there is no syringe volume to work out.

Safety

Side effects

  • The Russian prescribing information lists one adverse effect only: with prolonged use, mild irritation of the nasal mucosa 8
  • Allergic reactions are reported rarely; they are not in that one-line label list 8
  • Restlessness, irritability or anxious feelings are reported anecdotally, possibly consistent with the reported monoaminergic effects
  • A label that lists a single adverse effect and states that no overdose phenomena were seen even at substantially raised single doses 8 is describing limited systematic safety monitoring, not demonstrated safety

Do not use if

  • The Russian prescribing information contraindicates: hypersensitivity to the components, pregnancy, breastfeeding, acute psychoses, anxiety disorders accompanied by delusions and hallucinations, and a history of seizures 8
  • Note that acute psychosis and a seizure history are formal contraindications on that label, not merely cautions 8
  • The 0.1% product excludes children under 5 8
  • No long-term safety data; prolonged continuous use has not been studied

Interactions

Not systematically studied. The Russian prescribing information states that pharmaceutical incompatibility is unlikely given the peptide's rapid degradation, that other medicines are not expected to affect its absorption, and that concurrent intranasal vasoconstrictors should be avoided 8 - that last point is the only concrete instruction there. Interactions with dopaminergic and serotonergic medication are theoretically conceivable given the monoamine effects reported in animals, but no formal interaction study has been published.

Common questions

What is Semax used for?
Semax is a short peptide derived from the hormone ACTH, registered in Russia for stroke and cognitive/neurological indications and used off-label for focus and neuroprotection. Outside a few countries it is an unapproved research chemical.
Does Semax actually work?
It has small registered-use trials behind it in Russia, but the evidence is thin and mostly Russian-language, with limited independent replication. A registered indication in one country is not the same as proven benefit in healthy people.
What is the difference between Semax and N-Acetyl Semax Amidate?
N-Acetyl Semax Amidate is a chemically modified, longer-lasting analogue sold as a research chemical — not the registered Russian drug, and with even less direct evidence.

Sources