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Semax Research Evidence

The Semax evidence base: trials, journals, and what the data does not yet show.

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Compiled from published research · Last updated 2026-08-18T00:00:00.000Z

Key Findings at a Glance

• Semax is derived from ACTH but has been engineered to retain cognitive effects while completely eliminating the steroidogenic activity of its parent hormone. • Semax has been approved in Russia as a prescription medication since the 1990s for stroke recovery and cognitive disorders, giving it more real-world clinical data than most research peptides. • Semax upregulates both BDNF and NGF simultaneously, a dual neurotrophic effect that is uncommon among nootropic compounds and may explain its broad cognitive benefits. • Unlike stimulant-based cognitive enhancers, Semax builds its nootropic effects over days to weeks through neuroplasticity mechanisms rather than acute neurotransmitter manipulation.

Anxiolytic Effects

Studies demonstrate Semax produces anxiolytic (anti-anxiety) effects without the sedation, cognitive impairment, or dependence potential associated with benzodiazepine anxiolytics. Research in animal models shows reduced anxiety-related behaviors on established tests including the elevated plus maze, open field test, and light-dark box paradigms. The anxiolytic mechanism appears to involve modulation of serotonergic neurotransmission, effects on GABA systems, and increased enkephalin levels through inhibition of enkephalinase enzymes. Clinical observations in Russia suggest benefits for patients with anxiety disorders and stress-related conditions. Importantly, the anxiolytic effects occur alongside cognitive enhancement rather than at its expense, distinguishing Semax from traditional sedative anxiolytics. These properties make Semax relevant for research into anxiety disorders, performance anxiety, and stress-related cognitive impairment.

Trials and reviews

  • Kaplan crossover RCTNeurosci Res Commun1996

    double-blind placebo crossover · improved attention + working memory · N=30

  • Gusev ischemic stroke comparative studyZh Nevrol Psikhiatr1997

    improved neurological recovery vs conventional therapy · non-randomized · N=110

References

  1. Semax, an ACTH(4-10) analogue, and brain BDNF expression · Dolotov OV, et al. · 2006
  2. Dergunova LV, Filippenkov IB, Stavchansky VV, 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. · Filippenkov IB, Stavchansky VV, Denisova AE, Yuzhakov VV, Sevan'kaeva LE, Sudarkina OY, Dmitrieva VG, Gubsky LV, Myasoedov NF, Limborska SA, Dergunova LV · 2020
  3. [Results of the application of complex physiotherapeutic neurostimulation in optical neuropathies of various genesis]. · Dragon AK, Korchazhkina NB, Sheludchenko VM et al. · 2022
  4. The peptide semax affects the expression of genes related to the ... · Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV · 2014
  5. Functional Connectomic Approach to Studying Selank and Semax Effects. · Panikratova YR, Lebedeva IS, Sokolov OY et al. · 2020
  6. [Evaluation of therapeutic effect of new Russian drug semax in optic ... · Polunin GS, Nurieva SM, Baiandin DL, Sheremet NL, Andreeva LA · 2000
  7. Shadrina MI, Dolotov OV, Grivennikov IA, et al. Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action. J Mol Neurosci. 2010;41(1):30-35. · Shadrina M, Kolomin T, Agapova T, Agniullin Y, Shram S, Slominsky P, Lymborska S, Myasoedov N · 2010
  8. Effects of Semax on the Default Mode Network of the Brain. · Lebedeva IS, Panikratova YR, Sokolov OY et al. · 2018
  9. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus · Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Kamensky AA, Grivennikov IA, Myasoedov NF, Engele J · 2006
  10. Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005;30(12):1493-1500. · Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS · 2005
  11. Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials. · Charland SL, Stanek EJ · 2014
  12. Kaplan AY, Kochetova AG, Nezavibathko VN, Rzhevskii DA, Roshchina IF, Ashmarin IP. 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(2):306-310. · Tsai SJ · 2007
  13. Diagnostic Value of Different 3-D Shear Wave Elastography Sections in the Diagnosis of Thyroid Nodules. · Hu Z, Lu M, Wang X et al. · 2022
All Semax sections

Adamax

longevity & brainFgrade

A synthetic nonapeptide analog of Semax with N-terminal acetylation and adamantyl C-terminal modification, studied for enhanced BDNF signaling and blood-brain barrier penetration.

Selank

focus & cognitionCgrade

A tuftsin-derived anxiolytic nootropic that lowers anxiety and supports calm focus without sedation or dependence.

Dihexa

focus & cognitionFgrade

An oral angiotensin IV analog studied as a memory aid in rodents — the foundational animal paper now carries a formal notice of concern, and no human trial exists.

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