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Research information only. Not medical advice. 18+ only. Not FDA-approved for human therapeutic use.

Semax

Also known as: ACTH(4-10) analogue, ACTH(4-7)PGP, Met-Glu-His-Phe-Pro-Gly-Pro, MEHFPGP, Semax peptide, ACTH4-7-Pro-Gly-Pro

Synthetic nootropic/neuroprotective heptapeptide; melanocortin-related peptide; ACTH analogue

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What it is

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analogue of the N-terminal ACTH(4-10) fragment that is devoid of hormonal activity. Its documented or proposed mechanisms include: (1) upregulation of NGF and BDNF gene expression in the hippocampus, frontal cortex, and retina (PMID 19662538; PMID 7); (2) modulation of GABA-activated ionic currents (potentiation in cerebellar Purkinje cells) and inhibition of glycine-activated chloride currents in hippocampal pyramidal neurons; (3) modulation of intracellular calcium dynamics in hippocampal pyramidal neurons; (4) suppression of proinflammatory gene expression (Il1a, Il1b, Il6, Ccl3, Cxcl2) and activation of neurotransmission-related genes under ischemic conditions (PMID 34097675; PMID 32580520); (5) high-affinity chelation of Cu(II) ions, enabling extraction of copper from Cu-Aβ complexes and reduction of associated ROS production (PMID 40496623; PMID 35080861); (6) inhibition of enkephalin-degrading enzymes in human serum (IC50 10 µM); (7) modulation of brain functional connectivity, particularly affecting the default mode network and amygdala–temporal cortex connectivity (PMID 30225715; PMID 32342318); (8) targeting the µ-opioid receptor (Oprm1), regulating USP18 and deubiquitination of FTO to promote lysosomal membrane stability after spinal cord injury; (9) regulation of VEGF family gene expression in ischemic brain tissue (PMID 56; PMID 52); (10) immunomodulatory effects via immune response gene expression changes (PMID 24661604; PMID 42021992); (11) antioxidant properties demonstrated by counteracting heavy metal-induced learning inhibition. Metabolically, Semax is cleaved into functional fragments (HFPGP, PGP) that form a "synacton" with distinct receptor binding characteristics.

Class: Synthetic nootropic/neuroprotective heptapeptide; melanocortin-related peptide; ACTH analogue

What it's studied for

  • Ischemic stroke — neuroprotection and functional recovery Mixed
    • In 110 post-ischemic stroke patients, semax (6000 mcg/day x 10 days, 2 courses with 20-day interval) increased plasma BDNF levels and accelerated Barthel index improvement regardless of rehabilitation timing. PMID 29798983 Gusev et al. (2018). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova.
    • In 30 acute hemispheric ischemic stroke patients, Semax combined with conventional therapy improved regression of neurological deficits; most effective doses were 12 mg/day (moderate stroke) and 18 mg/day (severe stroke) for 5–10 days. PMID 11517472 Gusev et al. (1997). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova.
    • RNA-Seq in rat tMCAO model showed Semax suppressed inflammation-related genes and activated neurotransmission-related genes at 24 h after ischemia-reperfusion. PMID 32580520 Filippenkov et al. (2020). Genes.
    • In rat tMCAO model, Semax upregulated active CREB, downregulated MMP-9, c-Fos, and active JNK at 24 h, consistent with suppression of inflammation/cell death and activation of recovery. PMID 34201112 Sudarkina et al. (2021). International Journal of Molecular Sciences.
    • Genome-wide transcriptional analysis in rat pMCAO model showed Semax predominantly enhanced expression of immune-response genes and vascular-system genes at 3 and 24 h after occlusion. PMID 24661604 Medvedeva et al. (2014). BMC Genomics.
    • In rat global ischemia model, Semax increased proliferation of neuroglia, blood vessel endothelium, and progenitor cells in subventricular zone, and abated manifestation of ischemic damage. PMID 20617398 Stavchansky et al. (2011). Journal of Molecular Neuroscience.
  • Cerebrovascular insufficiency — disease progression prevention Human observational
    • In 187 patients with cerebrovascular insufficiency, Semax treatment resulted in significant clinical improvement, disease stabilization, and reduced risk of stroke/TIA, with minor side effects and good tolerability including in older patients. PMID 15792140 Gusev et al. (2005). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova.
  • Optic nerve disease and glaucomatous optic neuropathy Human observational
    • Semax administered intranasally or by endonasal electrophoresis improved visual acuity, visual field, optic nerve electrical sensitivity/conductivity, and color vision in patients with optic nerve diseases. PMID 10741256 Polunin et al. (2000). Vestnik oftalmologii.
    • Neuroprotective therapy including semax showed advantages over traditional treatment for glaucoma patients with normalized intraocular pressure, attributed to semax's neuroprotective and neurotrophic effects. PMID 11569188 Kurysheva et al. (2001). Vestnik oftalmologii.
  • Peptic ulcer — adjunct healing Human observational
    • Intranasal Semax (1% solution, 2–4 drops 3 times/day for 10 days) combined with standard antiulcer therapy resulted in ulcer healing in 89.5% of patients by day 14, vs. 30.8% in controls. PMID 12459874 Ivanikov et al. (2002). Bulletin of Experimental Biology and Medicine.
  • Alzheimer's disease — amyloid aggregation inhibition and cognitive improvement Mixed
    • In artificial membrane models, Semax prevented formation of Aβ:Cu complexes and exhibited anti-aggregating and cytoprotective properties, particularly in the presence of Cu²⁺. PMID 35080861 Sciacca et al. (2022). ACS Chemical Neuroscience.
    • Semax extracted Cu(II) from Cu-Aβ species, reduced redox cycling and ROS production in vitro, and showed cytoprotective properties for SH-SY5Y cells. PMID 40496623 Tomasello et al. (2025). Bioinorganic Chemistry and Applications.
    • In APPswe/PS1dE9/Blg transgenic Alzheimer's disease mice, Semax improved cognitive functions (open field, novel object recognition, Barnes maze) and reduced amyloid inclusions in cortex and hippocampus. PMID 41479572 Radchenko et al. (2025). Acta Naturae.
  • Spinal cord injury — functional recovery Animal studies only
    • Semax improved functional recovery in female C57BL/6 SCI mice, inhibited LMP-related pyroptosis, decreased oxidative stress, regulated USP18 via µ-opioid receptor targeting, and promoted deubiquitination of FTO. PMID 40692165 Liu et al. (2025). British Journal of Pharmacology.
  • Antidepressant / antistress effects Animal studies only
    • In male rats with chronic unpredictable stress, daily intraperitoneal Semax (60 nmol/kg BW) reversed CUS-induced anhedonia, body weight gain suppression, adrenal hypertrophy, and decreased hippocampal BDNF levels. PMID 39442746 Inozemtseva et al. (2024). European Journal of Pharmacology.
    • Semax attenuated effects of chronic unpredictable stress in rats (no abstract text available beyond title/MeSH). PMID 24385169 Yatsenko et al. (2013). Doklady Biological Sciences.
  • Nootropic effects — learning and memory Mixed
    • Semax counteracted heavy metal-induced inhibition of avoidance conditioning in rats, comparable in effect to ascorbic acid, confirming antioxidant/nootropic properties. PMID 27411820 Inozemtsev et al. (2016). Doklady Biological Sciences.
    • Intraperitoneal Semax (0.05 mg/kg) accelerated acquisition of one-way active avoidance and stimulated avoidance restoration after functional disturbances in shuttle-box in rats. PMID 25464761 Inozemtsev et al. (2013). Zhurnal vysshei nervnoi deiatelnosti.
    • Intranasal 1% Semax in healthy volunteers produced a greater volume of the default mode network rostral subcomponent vs. placebo on resting-state fMRI at 5 and 20 min post-administration. PMID 30225715 Lebedeva et al. (2018). Bulletin of Experimental Biology and Medicine.
    • In 52 healthy participants, Semax and Selank showed distinct and general effects on functional connectivity between right amygdala and right temporal cortex on resting-state fMRI. PMID 32342318 Panikratova et al. (2020). Doklady Biological Sciences.
  • Attention-deficit hyperactivity disorder (ADHD) and Rett syndrome — hypothesized therapeutic potential Animal studies only
    • Hypothesis paper proposing Semax as a potential ADHD and Rett syndrome therapy based on its ability to augment dopamine release, stimulate central BDNF synthesis, improve selective attention, and modulate brain development in animal studies. PMID 16996699 Tsai (2007). Medical Hypotheses.
  • Parkinson's disease — behavioral effects Animal studies only
    • In 6-OHDA rat PD model, Semax did not affect motor activity or passive defensive behavior; Selank (but not Semax) decreased anxiety in elevated cross-shaped maze. PMID 28702721 Slominsky et al. (2017). Doklady Biological Sciences.
  • Audiogenic epilepsy — neonatal intervention Animal studies only
    • Neonatal injection of Semax (days 2–7 of life) significantly reduced predisposition to audiogenic epilepsy in one-month-old DBA/2J mice. PMID 19145359 Boyarshinova et al. (2008). Bulletin of Experimental Biology and Medicine.
  • Neonatal stress / maternal deprivation — behavioral correction Animal studies only
    • Intranasal Semax (0.05 mg/kg, postnatal days 15–28) weakened impact of maternal deprivation on body weight and normalized anxiety levels in adolescent rats. PMID 22803132 Volodina et al. (2012). Bulletin of Experimental Biology and Medicine.
    • Intranasal Semax (50 µg/kg, postnatal days 15–28) after neonatal isolation reduced metabolic dysfunction and normalized corticosterone stress response in white rats. PMID 22708068 Volodina et al. (2012). Acta Naturae.
  • Immunomodulation Animal studies only
    • Semax acted as an effective immune corrector in a social stress model, restoring cellular and humoral immunogenesis reactions and phagocytic activity of neutrophils in rats. PMID 31028579 Samotrueva et al. (2019). Bulletin of Experimental Biology and Medicine.
  • Stress-induced gastrointestinal and hepatic protection Animal studies only
    • Intraperitoneal ACTH(4-7)PGP (Semax) (5, 50, 150, 450 µg/kg) before restraint stress reduced corticosterone, alleviated colon wall pathomorphological changes, and promoted intestinal adaptation in rats. PMID 33459919 Svishcheva et al. (2021). Bulletin of Experimental Biology and Medicine.
    • Intraperitoneal Semax (5, 50, 150, 450 µg/kg) in chronic emotional and painful stress normalized hepatocyte protein synthesis function and serum ALT activity in rats in a dose-dependent manner. PMID 28577097 Ivanov et al. (2017). Bulletin of Experimental Biology and Medicine.
  • Early-life SSRI exposure — behavioral and neurochemical correction Animal studies only
    • Semax administration (postnatal days 15–28) after neonatal fluvoxamine exposure reduced anxiety-like behaviour, improved learning, and normalized brain biogenic amine levels in rats. PMID 33418449 Glazova et al. (2021). Neuropeptides.
  • Neurodegenerative disease (general) — oxidative stress and neuroinflammation modulation Mixed
    • Review: Semax identified among bioactive peptides modulating oxidative stress, neuroinflammation, mitochondrial preservation, and synaptic plasticity in neurodegenerative disease models. PMID 41004910 Giri & Chandra (2025). Neuropeptides.

Community-reported dosing

RouteDoseFrequency / DurationPopulation / contextSource tier
Not specified (standard regimen)6000 mcg/day10 days per course; 2 courses with 20-day intervalhumanResearch PMID 29798983
Not specified12 mg/day (moderate stroke); 18 mg/day (severe stroke)5–10 dayshumanResearch PMID 11517472
Intranasal1% solution, 2–4 drops 3 times a day10 dayshumanResearch PMID 12459874
Intranasal1% Semax (single administration)Single dose; fMRI at 5 and 20 min post-injectionhumanResearch PMID 30225715
Intranasal0.05 mg/kgPostnatal days 15–28 (daily)animalResearch PMID 22803132
Intranasal50 µg/kgPostnatal days 15–28 (daily)animalResearch PMID 22708068
Intraperitoneal60 nmol/kg of body weightDaily during chronic unpredictable stress protocolanimalResearch PMID 39442746
Intraperitoneal5, 50, 150, and 450 µg/kgSingle administration 12–15 min before restraint stress modelinganimalResearch PMID 33459919
Intraperitoneal5, 50, 150, 450 µg/kg12–15 min before chronic restraint stress sessionsanimalResearch PMID 32737723
Intraperitoneal5, 50, 150, and 450 µg/kgChronic emotional and painful stress modelanimalResearch PMID 28577097
Intraperitoneal5, 50, 150, 450 µg/kgSingle administration before restraint stressanimalResearch PMID 38459919
Intraperitoneal0.05 mg/kgSingle administration (avoidance conditioning sessions)animalResearch PMID 25464761
Bath application (brain slice)1 µM (in vitro/ex vivo slice preparation)Single application to brain slicesanimalResearch PMID 41171324
Perfusion solution (in vitro)0.1 µM and 1 µMSingle application (concentration-clamp experiment)animalResearch PMID 29577196
In vitroIC50 10 µMIn vitro assayin_vitroResearch PMID 11443939
intranasal300 mcgonce dailybiohackers and nootropic users seeking cognitive enhancement[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal600 mcgonce dailyexperienced biohackers and nootropic users[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal900 mcgonce dailyexperienced biohackers comfortable with nootropic peptides[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal300 mcgtwice daily (morning and midday)biohackers optimizing for sustained daily cognitive output[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal600 mcgtwice daily (morning and midday)experienced nootropic users seeking maximal daily cognitive enhancement[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection50 mcgonce dailybiohackers preferring injectable administration for enhanced bioavailability[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgonce dailybiohackers using injectable peptides for cognitive or neuroprotective purposes[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection200 mcgonce dailyexperienced injectable peptide users seeking stronger cognitive or neuroprotective effects[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal600 mcgonce daily, taken acutely before demanding cognitive tasksstudents, professionals, and biohackers using Semax situationally[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal300 mcgonce dailyusers with anxiety, depression, or seeking mood stabilization alongside cognitive benefits[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal600 mcgonce dailybiohackers stacking Semax with Selank for synergistic nootropic and anxiolytic effects[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal900 mcgonce dailyprofessionals and students using Semax as a weekday cognitive enhancer[S] Claude Sonnet 4.6 — synthesized from aggregate training data

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

Safety signals

  • Minor side-effect profile reported in 187 patients with cerebrovascular insufficiency; well-tolerated including in older age groups — specific adverse events not detailed in abstract PMID 15792140
  • N-terminal acetylation of Semax (Ac-Semax) did not protect SH-SY5Y neuroblastoma cells from Cu(II)-induced cytotoxicity, unlike parent Semax — suggesting modification may alter safety/efficacy profile PMID 27586814
  • Neonatal Semax injection had strain-specific effects on audiogenic epilepsy susceptibility in mice; no effect in 4 of 5 strains tested PMID 19145359
  • Non-approved peptide with limited long-term safety data and absence of systematic clinical validation noted in narrative review PMID 42021992

References

  1. [1] PMID 29798983 — In 110 post-ischemic stroke patients, semax (6000 mcg/day x 10 days, 2 courses with 20-day interval) increased plasma BDNF levels and accelerated Barthel index
  2. [2] PMID 11517472 — In 30 acute hemispheric ischemic stroke patients, Semax combined with conventional therapy improved regression of neurological deficits; most effective doses we
  3. [3] PMID 32580520 — RNA-Seq in rat tMCAO model showed Semax suppressed inflammation-related genes and activated neurotransmission-related genes at 24 h after ischemia-reperfusion.
  4. [4] PMID 34201112 — In rat tMCAO model, Semax upregulated active CREB, downregulated MMP-9, c-Fos, and active JNK at 24 h, consistent with suppression of inflammation/cell death an
  5. [5] PMID 24661604 — Genome-wide transcriptional analysis in rat pMCAO model showed Semax predominantly enhanced expression of immune-response genes and vascular-system genes at 3 a
  6. [6] PMID 20617398 — In rat global ischemia model, Semax increased proliferation of neuroglia, blood vessel endothelium, and progenitor cells in subventricular zone, and abated mani
  7. [7] PMID 15792140 — In 187 patients with cerebrovascular insufficiency, Semax treatment resulted in significant clinical improvement, disease stabilization, and reduced risk of str
  8. [8] PMID 10741256 — Semax administered intranasally or by endonasal electrophoresis improved visual acuity, visual field, optic nerve electrical sensitivity/conductivity, and color
  9. [9] PMID 11569188 — Neuroprotective therapy including semax showed advantages over traditional treatment for glaucoma patients with normalized intraocular pressure, attributed to s
  10. [10] PMID 12459874 — Intranasal Semax (1% solution, 2–4 drops 3 times/day for 10 days) combined with standard antiulcer therapy resulted in ulcer healing in 89.5% of patients by day
  11. [11] PMID 35080861 — In artificial membrane models, Semax prevented formation of Aβ:Cu complexes and exhibited anti-aggregating and cytoprotective properties, particularly in the pr
  12. [12] PMID 40496623 — Semax extracted Cu(II) from Cu-Aβ species, reduced redox cycling and ROS production in vitro, and showed cytoprotective properties for SH-SY5Y cells.
  13. [13] PMID 41479572 — In APPswe/PS1dE9/Blg transgenic Alzheimer's disease mice, Semax improved cognitive functions (open field, novel object recognition, Barnes maze) and reduced amy
  14. [14] PMID 40692165 — Semax improved functional recovery in female C57BL/6 SCI mice, inhibited LMP-related pyroptosis, decreased oxidative stress, regulated USP18 via µ-opioid recept
  15. [15] PMID 39442746 — In male rats with chronic unpredictable stress, daily intraperitoneal Semax (60 nmol/kg BW) reversed CUS-induced anhedonia, body weight gain suppression, adrena
  16. [16] PMID 24385169 — Semax attenuated effects of chronic unpredictable stress in rats (no abstract text available beyond title/MeSH).
  17. [17] PMID 27411820 — Semax counteracted heavy metal-induced inhibition of avoidance conditioning in rats, comparable in effect to ascorbic acid, confirming antioxidant/nootropic pro
  18. [18] PMID 25464761 — Intraperitoneal Semax (0.05 mg/kg) accelerated acquisition of one-way active avoidance and stimulated avoidance restoration after functional disturbances in shu
  19. [19] PMID 30225715 — Intranasal 1% Semax in healthy volunteers produced a greater volume of the default mode network rostral subcomponent vs. placebo on resting-state fMRI at 5 and
  20. [20] PMID 32342318 — In 52 healthy participants, Semax and Selank showed distinct and general effects on functional connectivity between right amygdala and right temporal cortex on
  21. [21] PMID 16996699 — Hypothesis paper proposing Semax as a potential ADHD and Rett syndrome therapy based on its ability to augment dopamine release, stimulate central BDNF synthesi
  22. [22] PMID 28702721 — In 6-OHDA rat PD model, Semax did not affect motor activity or passive defensive behavior; Selank (but not Semax) decreased anxiety in elevated cross-shaped maz
  23. [23] PMID 19145359 — Neonatal injection of Semax (days 2–7 of life) significantly reduced predisposition to audiogenic epilepsy in one-month-old DBA/2J mice.
  24. [24] PMID 22803132 — Intranasal Semax (0.05 mg/kg, postnatal days 15–28) weakened impact of maternal deprivation on body weight and normalized anxiety levels in adolescent rats.
  25. [25] PMID 22708068 — Intranasal Semax (50 µg/kg, postnatal days 15–28) after neonatal isolation reduced metabolic dysfunction and normalized corticosterone stress response in white
  26. [26] PMID 31028579 — Semax acted as an effective immune corrector in a social stress model, restoring cellular and humoral immunogenesis reactions and phagocytic activity of neutrop
  27. [27] PMID 33459919 — Intraperitoneal ACTH(4-7)PGP (Semax) (5, 50, 150, 450 µg/kg) before restraint stress reduced corticosterone, alleviated colon wall pathomorphological changes, a
  28. [28] PMID 28577097 — Intraperitoneal Semax (5, 50, 150, 450 µg/kg) in chronic emotional and painful stress normalized hepatocyte protein synthesis function and serum ALT activity in
  29. [29] PMID 33418449 — Semax administration (postnatal days 15–28) after neonatal fluvoxamine exposure reduced anxiety-like behaviour, improved learning, and normalized brain biogenic
  30. [30] PMID 41004910 — Review: Semax identified among bioactive peptides modulating oxidative stress, neuroinflammation, mitochondrial preservation, and synaptic plasticity in neurode
  31. [31] PMID 32737723 — 5, 50, 150, 450 µg/kg Intraperitoneal (animal)
  32. [32] PMID 38459919 — 5, 50, 150, 450 µg/kg Intraperitoneal (animal)
  33. [33] PMID 41171324 — 1 µM (in vitro/ex vivo slice preparation) Bath application (brain slice) (animal)
  34. [34] PMID 29577196 — 0.1 µM and 1 µM Perfusion solution (in vitro) (animal)
  35. [35] PMID 11443939 — IC50 10 µM In vitro (in_vitro)
  36. [36] PMID 27586814 — N-terminal acetylation of Semax (Ac-Semax) did not protect SH-SY5Y neuroblastoma cells from Cu(II)-induced cytotoxicity, unlike parent Semax — suggesting modifi
  37. [37] PMID 42021992 — Non-approved peptide with limited long-term safety data and absence of systematic clinical validation noted in narrative review
  38. [38] PMID 19662538 — in-prose reference
  39. [39] PMID 7 — in-prose reference
  40. [40] PMID 34097675 — in-prose reference
  41. [41] PMID 56 — in-prose reference
  42. [42] PMID 52 — in-prose reference
  43. [43] PMID 27921334 — in-prose reference
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