Peptides & growth hormone

Semax

Updated · 28 sources · Editorial policy

Semax is a synthetic seven-amino-acid peptide developed in Russia from a fragment of adrenocorticotropic hormone (ACTH, the pituitary hormone that drives cortisol release). It keeps a short ACTH segment linked to memory and attention in animal work and adds a three-amino-acid tail to make it more resistant to breakdown. It is given as a nasal solution and is studied as a nootropic (cognition-targeting) and neuroprotective agent, mainly for stroke.

The single most important fact: the clinical evidence comes almost entirely from small Russian studies, published in Russian, from groups linked to its developers. The abstracts describe mostly open or non-randomized designs, and no independent placebo-controlled trial has been published. Semax is not approved by the FDA, and FDA has flagged it as a bulk drug substance with potential safety risks for compounding.

This page summarizes what the published studies and regulators report. It is for education only and is not medical advice.

Property Detail
Class Synthetic regulatory peptide; ACTH(4–10) analog without reported hormonal activity
Structure 7 amino acids; formula C₃₇H₅₁N₉O₁₀S, molecular weight 813.9 g/mol (PubChem)
Route in studies Mainly intranasal (nasal drops or solution); injection in a few studies
Doses in cited trials 6 mg/day (stroke rehabilitation); 12–18 mg/day (acute stroke); 12 mg/day (motor neuron disease)
Proposed mechanisms Raises BDNF in rat brain; slows enkephalin breakdown in human serum (test tube); modulates dopamine and serotonin in rodents
Human half-life No published human pharmacokinetic data found
US status Not FDA-approved; FDA lists it among bulk substances with safety concerns for compounding
New Zealand Named by Medsafe in a 2025 proposal to make ACTH analogs prescription medicines
WADA status Not named on the 2026 Prohibited List

What it is

Semax combines the ACTH fragment at positions 4–7 with a proline–glycine–proline tail in place of positions 8–10. Its developers added that tail to protect the peptide from peptidases (enzymes that cut peptides) (Filippenkov et al., Genes 2020). It is usually described as an ACTH(4–10) analog. PubChem lists it under CID 9811102, CAS number 80714-61-0 (PubChem).

Semax was developed by Russian researchers, and much of the research on it comes from the Institute of Molecular Genetics of the Russian Academy of Sciences (Medvedeva et al., BMC Genomics 2014). A 1997 review by its developers described 15 years of work and said the peptide had gone “from fundamental investigations to practical usage” in patients with central nervous system disease (Ashmarin et al., 1997). Unlike full-length ACTH, Semax is reported to lack hormonal (cortisol-releasing) activity (Tsai, Med Hypotheses 2007).

The library has separate pages for two related peptides. Selank is a Russian sibling built the same way: a natural peptide fragment (from tuftsin, an immune peptide) plus the same proline–glycine–proline tail. ADAMAX is sold online as a modified Semax with extra end groups; no study of ADAMAX itself has been published.

Peptide Built from Main research focus Human data
Semax ACTH(4–7) + Pro-Gly-Pro Stroke, cognition, optic nerve disease Small Russian clinical studies
Selank Tuftsin + Pro-Gly-Pro Anxiety Small Russian clinical studies
ADAMAX Semax with acetyl and adamantane end groups (as marketed) None published None

Proposed mechanisms

All mechanism data come from cell, tissue and animal studies:

  • BDNF. Brain-derived neurotrophic factor (BDNF) is a protein that supports nerve-cell growth and plasticity. In rats, intranasal Semax at 50 and 250 µg/kg raised BDNF protein in the basal forebrain within 3 hours, but not in the cerebellum. Rat brain membranes also had specific, high-affinity binding sites for Semax (Dolotov et al., J Neurochem 2006).
  • Enkephalin breakdown. In human serum in the test tube, Semax inhibited enzymes that break down enkephalins (natural opioid peptides), with an IC50 of 10 µM, versus 20 µM for selank (Kost et al., Bioorg Khim 2001).
  • Dopamine and serotonin. In rodents, Semax (0.15 mg/kg injected) raised extracellular levels of a serotonin breakdown product in the striatum to as much as 180% of baseline over 1–4 hours, without changing dopamine on its own. Given before D-amphetamine, it strongly enhanced amphetamine’s effect on dopamine release and on movement (Eremin et al., Neurochem Res 2005).
  • Gene expression after stroke. In rats with experimental stroke, Semax changed the expression of many brain genes, mainly immune- and blood-vessel-related genes (Medvedeva et al., 2014).

How it behaves in the body

There are no published human pharmacokinetic studies, so its human half-life, bioavailability and duration of action are not known. The available data are from rats and cell cultures:

Finding Model Source
0.093% of the dose per gram of brain tissue 2 minutes after a 50 µg/kg intranasal dose; 80% of that was intact Semax Rats, tritium-labeled peptide Shevchenko et al., Bioorg Khim 2006
Rapid enzymatic breakdown; the Pro-Gly-Pro fragment predominated in samples Rats Shevchenko et al., 2006
Main breakdown steps remove the first two and last two amino acids, leaving five-amino-acid fragments Rat brain cell cultures and membranes Zolotarev et al., Amino Acids 2006

The developers’ 1997 review reported that effects on memory and attention lasted 20–24 hours after a single intranasal dose of 0.015–0.050 mg/kg in animals and people (Ashmarin et al., 1997). That reported duration is much longer than the peptide’s measured survival in rat tissue, and it has not been tested in independent pharmacokinetic studies.

About the half-life. We could not find any published measurement of Semax’s half-life in people. Short half-life figures quoted online are not traceable to a human study and should be treated as unverified.

Regulatory status

  • United States. Semax is not an FDA-approved drug. FDA placed “Semax (heptapeptide)” in category 2 of bulk drug substances nominated for compounding, the group FDA flags as potentially presenting significant safety risks. FDA cited a risk of immunogenicity (triggering an immune response) from aggregation and peptide-related impurities and said it has “no, or limited, safety-related information” for the proposed routes. FDA’s current page lists Semax among category 2 nominations later withdrawn by the nominators (FDA, category 2 bulk drug substances).
  • Russia. Semax has been used clinically in Russia for decades, according to its developers and a 2026 review that described it as not approved in the West (Ashmarin et al., 1997; Mavrych et al., Front Aging 2026). We could not access the Russian state drug register, so we do not state its exact registered indications.
  • New Zealand. In 2025, Medsafe proposed classifying all ACTH analogs as prescription medicines and named “Adamax and Semax” as examples marketed as cognitive enhancers. It noted limited clinical research and little knowledge of side effects or long-term effects (Medsafe, 2025). The committee deferred its decision in July 2025; Medsafe later recommended prescription-medicine classification (MCC 74th meeting minutes).
  • Controlled-substance status. Semax is not a scheduled anabolic steroid and is not named in 21 CFR 1308.13.
  • Sport. Semax is not named on the WADA 2026 Prohibited List. The list bans corticotrophins under S2.2.2, and its S0 class bans substances with no current government approval for human therapeutic use. Whether either class covers Semax depends on how its ACTH-fragment structure and Russian status are interpreted, which WADA has not stated publicly. Athletes should check with their anti-doping organization.

What the research shows

Stroke

Stroke is the most studied use. All of the trials below are Russian, published in Russian, and none is described in its abstract as randomized, placebo-controlled and blinded.

Study Patients Design (as described) Semax dose Reported result
Gusev et al., 1997 110 with acute hemispheric ischemic stroke 30 on Semax plus standard care vs 80 controls on standard care 12 mg/day (moderate) or 18 mg/day (severe) for 5–10 days Some faster recovery of neurological, especially motor, deficits
Gusev et al., 2005 187 with chronic cerebrovascular insufficiency Design not given in abstract Not given in abstract Reported clinical improvement and fewer strokes and transient ischemic attacks
Gusev et al., 2018 110 after ischemic stroke, in early (about day 89) or late (about day 214) rehabilitation Subgroups with and without Semax 6 mg/day in two 10-day courses, 20 days apart Higher plasma BDNF; faster and better recovery on the Barthel index (a scale of daily-living independence); smaller effect on weakness

The abstracts do not report effect sizes or confidence intervals, and the 2005 and 2018 abstracts do not say how patients were assigned to Semax. A 2026 review noted that there has been “no independent Western validation” of this evidence (Mavrych et al., 2026).

Other neurological and eye conditions

  • Motor neuron disease. In an open-label study of 27 patients given 12 mg/day intranasally in two 10-day courses, Semax did not change the course of nerve damage or clinical ALS ratings. It improved a quality-of-life score, mainly through mood and motivation (Serdiuk et al., 2007).
  • Optic nerve disease. Adding Semax nasal drops or endonasal electrophoresis to standard therapy was reported to improve visual acuity, visual fields and color vision compared with a control group; the abstract gives no patient numbers (Polunin et al., 2000).
  • Post-hypoxic brain injury. In 73 patients with long-term effects of oxygen deprivation, Semax helped those with memory problems. The authors also reported episodes of paroxysmal (seizure-like) EEG activity after some injections (Alekseeva et al., 1999).

Cognition and brain imaging in healthy people

Claims that Semax sharpens memory and focus in healthy people rest mainly on the developers’ own reports (Ashmarin et al., 1997). Two small imaging studies measured brain activity rather than performance:

  • In 24 healthy volunteers, intranasal 1% Semax (n = 14) versus placebo (n = 10) enlarged part of the default mode network (a set of brain regions active at rest) on functional MRI 5–20 minutes after dosing (Lebedeva et al., Bull Exp Biol Med 2018).
  • In 52 healthy adults given Semax, selank or placebo, Semax changed functional connectivity between the right amygdala and the right temporal cortex (Panikratova et al., Dokl Biol Sci 2020).

Neither study tested memory, attention or any clinical outcome. A 2007 paper proposed Semax for ADHD and Rett syndrome on the basis of animal data; it was a hypothesis, not a trial (Tsai, 2007).

Gut

In patients with peptic ulcers that had not healed on standard drugs, adding intranasal 1% Semax for 10 days was followed by healing by day 14 in 89.5% versus 30.8% of controls. The short report does not give patient numbers or describe randomization (Ivanikov et al., Bull Exp Biol Med 2002).

Muscle, recovery and performance

We found no human studies of Semax on muscle, tissue repair, body composition or athletic recovery. In female mice with spinal cord injury, Semax improved functional recovery, which the authors linked to the μ-opioid receptor (Liu et al., Br J Pharmacol 2025). A 2026 orthopedics review grouped Semax with selank and Dihexa as “neuroactive” peptides and noted a current lack of clinical trials (Rahman et al., JAAOS Glob Res Rev 2026). Animal results cannot be assumed to apply to people.

Side effects and risks

Limited safety data

The Russian studies describe Semax as well tolerated, including in older patients (Gusev et al., 2005). The developers’ review said it had produced no negative side effects in their experience (Ashmarin et al., 1997). These studies were small, short and not designed to detect uncommon harms, and no long-term safety studies have been published. FDA said it lacks sufficient information to know whether Semax would cause harm in humans (FDA).

Seizure-like EEG activity

In the post-hypoxic encephalopathy study, some patients showed paroxysmal EEG activity after Semax injection. The authors advised that the first dose be given with EEG monitoring (Alekseeva et al., 1999). No study has measured seizure risk in people with epilepsy.

Interactions with stimulants

In rodents, Semax markedly increased the dopamine release and hyperactivity caused by D-amphetamine (Eremin et al., 2005). No human interaction studies have been published.

Immunogenicity and product quality

FDA’s main stated concern is that peptide products made outside approved manufacturing can aggregate or contain peptide-related impurities that provoke an immune reaction. Sciensano, Belgium’s public-health laboratory, found Semax and selank in two suspicious seized preparations in 2017 and 2018. The authors noted that such peptides were sold freely online as injectable powders and nasal sprays (Vanhee et al., Drug Test Anal 2020). Products sold this way are outside regulatory quality control.

Key takeaways

  • An ACTH-fragment peptide from Russia. Semax joins a short piece of ACTH to a stabilizing three-amino-acid tail and is given intranasally; it is reported to lack ACTH’s hormonal activity.
  • Human evidence is small and mostly uncontrolled. Russian studies in stroke, optic nerve disease and other conditions reported benefits, but none is described as a blinded, randomized placebo-controlled trial, and none has been replicated independently.
  • Mechanism data come from animals and lab work. Proposed actions include raising BDNF, slowing enkephalin breakdown and modulating dopamine and serotonin.
  • No human half-life is published. Rat studies show rapid breakdown into smaller fragments.
  • Not approved in the US. FDA flagged Semax for immunogenicity and impurity risks and says human safety data are lacking; New Zealand is moving to make ACTH analogs prescription-only.
  • No evidence for muscle or recovery in people. The only injury-recovery data are from mice.

Sources

  1. Filippenkov IB, Stavchansky VV, Denisova AE, et al. Novel insights into the protective properties of ACTH(4-7)PGP (Semax) peptide at the transcriptome level following cerebral ischaemia-reperfusion in rats. Genes (Basel). 2020;11(6):681. PubMed.
  2. National Center for Biotechnology Information. Semax, PubChem CID 9811102. PubChem.
  3. Asmarin IP, Nezavibat’ko VN, Miasoedov NF, et al. A nootropic adrenocorticotropin analog 4-10-semax (15 years experience in its design and study) [in Russian]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997;47(2):420–430. PubMed.
  4. Tsai SJ. Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Med Hypotheses. 2007;68(5):1144–1146. PubMed.
  5. Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006;97(Suppl 1):82–86. PubMed.
  6. Kost NV, Sokolov OIu, Gabaeva MV, et al. Semax and selank inhibit the enkephalin-degrading enzymes from human serum [in Russian]. Bioorg Khim. 2001;27(3):180–183. PubMed.
  7. Eremin KO, Kudrin VS, Saransaari P, et al. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005;30(12):1493–1500. PubMed.
  8. Medvedeva EV, Dmitrieva VG, Povarova OV, et al. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics. 2014;15:228. PubMed.
  9. Shevchenko KV, Nagaev IIu, Alfeeva LIu, et al. Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration [in Russian]. Bioorg Khim. 2006;32(1):64–70. PubMed.
  10. Zolotarev YA, Dolotov OV, Inozemtseva LS, et al. Degradation of the ACTH(4-10) analog Semax in the presence of rat basal forebrain cell cultures and plasma membranes. Amino Acids. 2006;30(4):403–408. PubMed.
  11. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (category 2). Content current as of April 22, 2026. FDA.
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  14. Medicines Classification Committee. Minutes of the 74th meeting, 23 July 2025, item 5.7 Peptide groups. Medsafe.
  15. 21 CFR 1308.13, Schedule III. eCFR.
  16. World Anti-Doping Agency. The 2026 Prohibited List, in effect from January 1, 2026. WADA.
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  19. Gusev EI, Martynov MY, Kostenko EV, et al. The efficacy of semax in the tretament of patients at different stages of ischemic stroke [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(3 Vyp 2):61–68. PubMed.
  20. Serdiuk AV, Levitskiĭ GN, Miasoedov NF, Skvortsova VI. The study of chronic partial denervation and quality of life in patients with motor neuron disease treated with semax [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2007;107(4):29–39. PubMed.
  21. Polunin GS, Nurieva SM, Baiandin DL, et al. Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease [in Russian]. Vestn Oftalmol. 2000;116(1):15–18. PubMed.
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  23. Lebedeva IS, Panikratova YR, Sokolov OY, et al. Effects of Semax on the default mode network of the brain. Bull Exp Biol Med. 2018;165(5):653–656. PubMed.
  24. Panikratova YR, Lebedeva IS, Sokolov OY, et al. Functional connectomic approach to studying Selank and Semax effects. Dokl Biol Sci. 2020;490(1):9–11. PubMed.
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