Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide derived from the ACTH(4-7) fragment of adrenocorticotropic hormone, with the addition of a C-terminal Pro-Gly-Pro sequence for metabolic stability. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences beginning in the 1980s by Ashmarin and colleagues, who sought to identify ACTH-derived peptides with nootropic activity but without the hormonal effects of full-length ACTH.
The critical pharmacological distinction of Semax is that it retains the neurotrophic properties of the ACTH fragment while completely lacking the hormonal activity of full-length ACTH. Semax does not stimulate cortisol release from the adrenal glands. This separation of neurotrophic from hormonal effects makes it pharmacologically unique among ACTH-derived compounds.
Semax is approved in Russia and CIS countries as a prescription medication for a range of neurological conditions including ischemic stroke recovery, traumatic brain injury, optic nerve disease, and cognitive decline. It is listed on the Russian List of Vital & Essential Drugs. Available formulations include 0.1% (nootropic) and 1% (neuroprotective) intranasal solutions. In Western countries, it is classified as a research peptide and is not FDA or EMA approved.
The neuroprotective mechanism of Semax has been studied extensively at the transcriptomic level. Genome-wide analysis in ischemic stroke models shows that Semax dramatically shifts gene expression away from inflammatory pathways and toward neurotransmission and vascular repair pathways, modulating over 1,500 genes. In photothrombosis models, six daily administrations reduced infarction size and improved cognitive task performance.
The clinical literature behind Semax is nasal: the reference material for both vial strengths describes preparing a 0.1% intranasal solution and giving it drop by drop over a 10-day course, not drawing a subcutaneous amount. Converting those amounts into syringe units would need a nasal-to-injected conversion no source provides. No injectable amount, schedule or frequency for Semax is established anywhere, and none has been invented here. The reconstitution figures above are arithmetic and are correct; what is missing is an injectable schedule to apply them to.
Semax is a registered medicine in Russia, supplied as a 0.1% intranasal solution in which each drop of about 0.05 mL carries roughly 50 mcg, and the amounts in its published work range from 0.25 mg in early studies to several milligrams a day given over 10-day courses in stroke care. Those are nasal amounts delivered drop by drop, not injections, and converting them into syringe units would require a conversion no source provides — which is why the nasal course is described here rather than charted as a schedule. No injectable dose for Semax is established anywhere, and the dose-finding work behind it was published almost entirely in Russian-language journals without independent replication or Western regulatory review. Athena's 5 mg and 10 mg vials are listed on this page and the concentration arithmetic for them is exact; the amount and the schedule to measure out are what no source supplies.
What this evidence establishes. No independently established human dosing exists for Semax. It is a registered medicine in Russia and is supplied there as an intranasal solution, but the dose-finding work behind it was published almost entirely in Russian-language journals, has not been replicated outside Russia, and has not been through Western regulatory review. No injectable dose is established at all. The figures above are reconstitution arithmetic only.
For educational and laboratory research purposes only. It does not provide medical advice, dosing recommendations, or instructions for human or veterinary use. Syringe units assume a U-100 syringe, on which 1 mL is 100 units and a 50-unit syringe holds 0.5 mL.
Semax acts through multiple complementary neuroprotective and cognitive-enhancing pathways. Its exact receptor-level mechanism remains incompletely understood, but published research supports the following:
Rapidly increases BDNF mRNA and protein levels in the hippocampus and cortex through CREB-dependent transcription. Also upregulates TrkB receptor and NGF expression.
Activates dopaminergic and serotonergic brain systems in the striatum and frontal cortex without acting as a direct receptor agonist. Contributes to focus, motivation, and mood.
In ischemic stroke models, suppresses expression of inflammation-related genes and activates neurotransmission-related genes, compensating for ischemia-disrupted expression patterns.
Upregulates vascular endothelial growth factor (VEGF), promoting cerebral blood flow, angiogenesis, and vascular repair in ischemic tissue.
Shifts the Bcl-2/Bax balance toward cell survival, upregulating anti-apoptotic proteins and downregulating pro-apoptotic caspase-3 in neurons under stress.
Like its sibling compound Selank, inhibits enzymes that degrade enkephalins (IC50 ~10 mcM), preserving endogenous opioid-mediated stress modulation.
No hormonal activity: Despite being derived from ACTH, Semax does not activate the HPA axis, does not stimulate cortisol secretion, and has no adrenal or endocrine effects. The ACTH(4-7) fragment retains only the neurotrophic domain of the parent hormone.
Semax has safety data from over two decades of clinical use in Russia and CIS countries, plus published preclinical research. The following is derived from available literature:
| Condition / Factor | Risk Level | Rationale |
|---|---|---|
| Hormonal effects (cortisol, ACTH) | NONE | Despite ACTH derivation, Semax does not activate the HPA axis or stimulate adrenal cortisol production. No endocrine effects at therapeutic doses. |
| Concurrent SSRI/MAOI use | MODERATE (caution) | Semax modulates serotonergic and dopaminergic neurotransmission. Theoretical interaction with SSRIs, MAOIs, or other neuroactive compounds. Caution warranted. |
| Seizure disorders | MODERATE (theoretical) | Neuroactive peptides that modulate excitatory/inhibitory balance should be used with caution in patients with seizure history. Not specifically studied. |
| Pregnancy / breastfeeding | INSUFFICIENT DATA | No reproductive safety data published. Standard precaution for neuroactive peptides. |
| Poor oral bioavailability | LOW (route limitation) | As a peptide, Semax has poor oral bioavailability. Administered intranasally (primary) or subcutaneously. Not suitable for oral dosing. |
| Injection site / nasal irritation | LOW | Mild nasal irritation may occur with intranasal administration. Generally well-tolerated across published studies. |
| Overall clinical safety (Russian data) | FAVORABLE | Over 20 years of clinical use in Russia with excellent reported safety profile. Non-toxic, non-addictive. No serious adverse events documented in published literature. |
| International clinical data | LIMITED | Robust mechanistic and Russian clinical data. Limited independent international replication. Pilot fMRI study in Western subjects (n=24) confirmed CNS effects. |
Russia: Approved as a prescription medication in 0.1% (nootropic) and 1% (neuroprotective) intranasal formulations. Indicated for ischemic stroke recovery, traumatic brain injury, optic nerve atrophy, cognitive decline, and peptic ulcer disease. Listed on the Russian List of Vital & Essential Drugs since 2011.
FDA/EMA: Not approved. Classified as a research compound in the US and EU. No IND application has been filed with the FDA.
Availability: Available from peptide suppliers in intranasal and injectable formulations. The modified form N-Acetyl Semax Amidate offers improved stability. Used in integrative medicine and cognitive optimization practices globally.
Key distinction: Semax and Selank represent a paired Russian peptide development program from the same institute, targeting complementary neurological pathways. Semax leads with neuroprotection and cognitive drive (ACTH-derived, dopaminergic), while Selank leads with anxiolysis and emotional stabilization (tuftsin-derived, GABAergic). Both share enkephalinase inhibition and BDNF modulation. Both have Russian regulatory approval. Both lack Western regulatory validation. Together, they represent perhaps the most clinically advanced non-Western peptide pharmacology program in the world.
Test your understanding of Semax\'s ACTH-derived mechanism, neuroprotective profile, and clinical applications.
This profile is for educational and research purposes only. It is not medical advice, and nothing on it is a protocol, a recommendation, or an instruction for use in a person or an animal.
Athena Peptides Education does not prescribe, sell, or recommend any compound. Compounds discussed here are for laboratory research only and are not for human consumption. Always consult a qualified physician before making any decision about your health.