The six / Semax
Semax
Also: ACTH(4-7)-Pro-Gly-Pro, Met-Glu-His-Phe-Pro-Gly-Pro
The only one of the six that is a registered medicine somewhere: a Russian nasal drop with thirty years of use and almost no Western data.
Class
Synthetic heptapeptide, 7 amino acids, ACTH analogue
Sequence
Met-Glu-His-Phe-Pro-Gly-Pro
Origin
Institute of Molecular Genetics, Russian Academy of Sciences; registered in Russia 1996
Policy form
Semax free base
Permitted routes
Intranasal only
Human evidence
Low to moderate: Russian trials, small and unreplicated
What people ask for it for
Focus, memory, mental clarity and recovery after neurological events. It is the 'cognitive' peptide, asked about by people who want a non-stimulant option.
What the policy allows
Semax free base. Intranasal only. Injectable Semax, which some grey-market sellers offer, is outside the policy.
Strength of the evidence
Low to moderateSemax has something the other five lack: a human clinical record, including a 110-patient stroke study and an fMRI study in healthy volunteers. It is also single-country, developer-affiliated, methodologically thin by Western standards and not independently replicated.
Where it comes from
Semax was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It takes a four-amino-acid fragment of ACTH, the pituitary hormone, and adds a Pro-Gly-Pro tail that protects it from enzymes and extends its life in the body. The result keeps ACTH's effects on the brain without its hormonal effect on the adrenal glands.
It has been a registered medicine in Russia since 1996, as 0.1% nasal drops for cognitive and attention disorders and 1% drops for acute ischaemic stroke and optic nerve conditions. Russian neurologists have used it for three decades; almost none of that use has produced data in Western journals.
Outside Russia it circulates as a nootropic, usually as a nasal spray bought from research-chemical sellers.
How it is thought to work
From cell and animal models unless stated
In rat models Semax raises the expression of BDNF and NGF, the growth factors that support neuron survival and plasticity, in the cortex after induced stroke. This is the mechanism most of its reputation rests on.
It modulates serotonin and dopamine signalling in rodents and is reported to improve cerebral blood flow and reduce oxidative stress in neural tissue.
Intranasal delivery is the point of the design: the nose offers a route to the brain that avoids first-pass metabolism, which is why the policy permits that route and no other.
What the research shows
Study by study, labelled by what it was. The third column is the citation; the full references are at the foot of the page.
In cells and animals
Rat cerebral ischaemia
Increased BDNF and NGF gene activity and protective changes in brain protein expression.
PubMed 19633950; PubMed 34201112
Rodent neurochemistry
Increased serotonin activity and amplified dopamine release.
Neurochem Res, 2005
Global cerebral ischaemia in vivo
Improved survival and neurological outcome in treated animals.
PubMed 11188738
In people
Acute hemispheric ischaemic stroke, 110 patients (30 Semax, 80 controls), 1997
Better neurological recovery in the treated group on clinical and electrophysiological measures. Open, unbalanced, single centre.
PubMed 11517472
Acute ischaemic stroke, 1% Semax within 12 hours, Gusev et al., 2007
Improved neurological outcomes at day 5 and day 30 versus standard care.
Zh Nevrol Psikhiatr 2007
Post-stroke patients, 110, two 10-day courses, 2018
Reported functional improvement. Russian-language, developer-affiliated.
PubMed 29798983
Healthy volunteers, 24, resting-state fMRI, intranasal Semax versus placebo
A larger default mode network subcomponent in the treated group. A mechanistic finding, not a benefit.
PubMed 30225715
Optic nerve disease and chronic cerebrovascular insufficiency
Reported improvements; outcome details sparse in the available abstracts.
PubMed 10741256; PubMed 15792140
Safety, and what is not known
- The published record describes mild nasal irritation as the most common effect, occasional nasal dryness with extended use and rare transient headache. Most studies did not report side effects at all, which is a reporting gap rather than evidence of absence.
- An FDA adverse event report describes eye pain and burning after nasal drops bought online. One study noted a possible effect on clotting, a theoretical bleeding concern that has not been followed up.
- No cortisol, cardiovascular or dependence effects have been reported, which is consistent with the design: the ACTH fragment used does not stimulate the adrenal glands.
- There is no Western pharmacovigilance data and no long-term safety study. The policy's Appendix B cites the intranasal human record across several hundred subjects as reporting no adverse outcomes.
What the HHS policy says about Semax
Semax free base
Intranasal only. Injectable Semax, which some grey-market sellers offer, is outside the policy.
- Appendix B records updated characterisation data and an intranasal human record of several hundred subjects with no adverse outcomes reported.
- The free base is the permitted form, matching the registered Russian product; an acetate salt is not what the policy names.
All ten conditions of the policy →
Sport
Not named individually. WADA's S0 category prohibits substances not approved for human therapeutic use by any governmental health authority; Semax is approved in Russia, which makes its status less clear-cut than the others. A tested athlete should ask their federation.
Regulatory status
-
Never
FDA approval. No application for approval of this substance has been filed in the US, and no trial exists that could support one.
-
September 2023
Placed in Category 2 of FDA's interim 503A bulk substances list, the category for substances where FDA identified significant safety risks. Reputable pharmacies stopped compounding it.
-
April 2026
Removed from the active Category 2 table after the Federal Register notice announcing advisory committee review.
-
July 2026
Pharmacy Compounding Advisory Committee recommended it on July 24. FDA staff had opposed the recommendation. Tallies for the second day were not published in the sources we rely on.
-
October 28, 2026
Covered by the HHS enforcement discretion policy. Compoundable by state-licensed pharmacies and physicians that meet all ten of the policy's conditions, for an individual patient on a valid prescription. Still not on the 503A bulks list and still not approved.
Getting Semax through Healthy Peptides
You complete a health intake. An independent clinician at Beluga Health reviews it and decides whether Semax is appropriate for you, and by which permitted route. If prescribed, a state-licensed pharmacy that meets every condition of the HHS policy compounds the single-ingredient product and ships it to you. Healthy Peptides sells you the program; Local Healthcare bills you as its agent.
What we will and will not tell you
- WillWhat the research on Semax actually shows, graded honestly, and the routes a pharmacy may prepare.
- WillWho made it, who prescribed it, who billed you, and how to report a problem.
- Will notCall Semax approved, proven, safe or natural, or promise a result.
- Will notPublish a dose or protocol. That is between you, the clinician and the pharmacy label.
Questions about Semax
Is Semax approved anywhere?
In Russia, since 1996, as nasal drops for stroke, cognitive disorders and optic nerve conditions. It is not approved in the US, the EU or the UK. The HHS policy allows US pharmacies to compound it; it does not approve it.
What is the human evidence?
Russian trials in acute stroke, including a 110-patient study and a 2007 study at the 1% strength within 12 hours of stroke, reported better neurological recovery. An fMRI study in 24 healthy volunteers showed a measurable brain-network change. The trials are small, single-country and unreplicated.
Why nasal only?
Because intranasal is the route with the human record and the one Appendix B of the policy names. Injectable Semax is outside the policy, whatever a grey-market seller says.
Is it a stimulant?
No. It does not act through the stimulant pathways and no dependence has been reported. That is a statement about mechanism, not a guarantee of effect; the cognitive-enhancement claims in healthy people rest on small Russian studies.
What are the side effects?
Mild nasal irritation is the most reported. Dryness with long use and occasional headache are described. The gaps are in long-term and Western data, not in the signal so far.
Semax is not FDA-approved and no clinical trial has established that it is safe or effective for any use. The research described on this page is reported as what it is, cell, animal or small human studies, and is not a benefit you should expect. Programs are provided only where an independent, licensed clinician determines they are clinically appropriate after reviewing your health history, and not everyone qualifies. Compounded Semax is prepared by a state-licensed pharmacy under a patient-specific prescription and the conditions of the HHS enforcement discretion policy of October 28, 2026, which is not an approval and may be withdrawn. Availability varies by state. This page is general information, not medical advice. Last reviewed October 29, 2026.
Sources
- Effectiveness of Semax in the acute period of hemispheric ischaemic stroke (clinical and electrophysiological study). 1997
- Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischaemia. 2009
- Brain protein expression profile confirms the protective effect of the ACTH(4-7)PGP peptide (Semax) in a rat model of cerebral ischaemia-reperfusion. 2021
- Resting-state fMRI study of intranasal Semax in healthy volunteers. 2018
- Neuroprotective peptides and new strategies for ischaemic stroke drug discoveries (review). 2023
- Superpower peptide guide: Semax
- HHS: Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances, with Appendices A and B (October 28, 2026)
- AJMC: FDA panel backs 6 peptides for compounding (July 2026)
- FDA: Bulk drug substances used in compounding under section 503A
- WADA: 2026 Prohibited List