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Medical notice — For research and educational purposes only. Not medical advice. Consult a licensed physician before using any peptide or compound.

Semax

nootropicneuroprotectionfocuscognitive
Regulatory status — Research use only — not approved for human use

Semax (ACTH(4-7)PGP) is a synthetic heptapeptide derived from the adrenocorticotropic hormone (ACTH) fragment, investigated primarily for neuroprotective, anti-inflammatory, and cognitive-enhancing properties. The current evidence base consists entirely of animal and in vitro studies; no human randomized controlled trials have been conducted. Its mechanisms include modulation of gene expression in ischemia-affected brain regions, anti-inflammatory cytokine regulation, and copper chelation relevant to amyloid-beta pathology.

Evidence coverage

16/18 claims verified by independent fact-checker.

Pepteligence regenerates entries quarterly and when new high-tier evidence appears.

Quick facts

Half-life
—
Typical dose
See research context
Route
[insufficient evidence in research packet]
Frequency
[insufficient evidence in research packet]
Cycle length
—
Evidence strength
Animal models

Suggested labs for this peptide class — educational reference only; not medical advice.

TL;DR

  • Half-life: — — dosed —.
  • Administered via —.
  • Evidence base: animal model studies.
  • Primary goals: nootropic, neuroprotection, focus, cognitive.
EVIDENCE HIERARCHYRCTsObservationalAnimal studiesAnecdotal

Primarily animal data

How we evaluate evidence →

How it works

GLP-1 receptor agonists reduce appetite via hypothalamic signalling and enhance insulin secretion.

Semax (ACTH(4-7)PGP) is a synthetic analogue of the ACTH(4-10) fragment that exerts neuroprotective activity through several mechanistic pathways identified in animal and in vitro research. Animal studies indicate that Semax modulates differentially expressed genes associated with neuroprotection in ischemia-affected brain regions [2], and preliminary evidence from rat stroke models suggests that ACTH-like peptides including Semax compensate for disrupted brain gene expression profiles in the early post-stroke period [8]. Animal studies also indicate that Semax modulates the expression pattern of immune genes in rat brain following experimental stroke [9]. In a spinal cord injury model using male Sprague Dawley rats, animal studies indicate that ACTH4-10Pro8-Gly9-Pro10 (Semax) modulates anti-inflammatory cytokine expression, specifically upregulating IL-4, IL-10, and IL-13 [3]. Animal studies further indicate that Semax targets the μ opioid receptor gene Oprm1, promoting deubiquitination and contributing to functional recovery after spinal cord injury in female mice [1]. At a neuronal level, mechanistic data in rat brain neurons point to Semax increasing the frequency of spontaneous intracellular calcium fluctuations in pyramidal neurons of the hippocampal CA1 field [10]. Mechanistic data also suggest that synthetic corticotropins including Semax allosterically modulate the GABA-receptor system [11]. In vitro evidence indicates that Semax acts as a copper chelator, inhibiting Cu(II)-catalyzed reactive oxygen species production and cytotoxicity of amyloid-beta through metal ion stripping and redox silencing [6], and in vitro studies further indicate that Semax affects copper-induced amyloid-beta aggregation and amyloid formation in artificial membrane models [7]. All mechanistic pathways described here are derived from animal or in vitro data; human pharmacological confirmation is absent from the current evidence base.

What the research says

Research summary content coming soon. Check the references section for indexed studies.

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Approximate plasma concentration over 4 half-lives (0h × 4 = 0h)

Protocol lifecycle

BeforeDuringAfter

Before — Pre-cycle readiness

Readiness checklist

Evidence awareness
  • Understand that Semax has no human RCT data; all evidence is from animal or in vitro studies.
  • Understand that no human dosing, safety, or pharmacokinetic data are available in the peer-reviewed literature.
  • Consult a licensed healthcare provider before use; this compound is not approved for therapeutic use in any reviewed jurisdiction based on the current research packet.
  • [insufficient evidence in research packet — no human clinical protocols are available to inform pre-use preparation steps.]

During — Active protocol

Protocol notice — The following describes common protocols reported in research and community sources. This is not medical advice. Dosing, frequency, and duration should be determined with a licensed physician familiar with peptide research.
  • [insufficient evidence in research packet — no human clinical trial data exist to guide in-cycle monitoring or protocol adjustments.]

After — Post-cycle

  • [insufficient evidence in research packet — no human clinical data support cycling or post-cycle recommendations.]

Stacks it appears in

Semax is typically used as a standalone compound. Stack data coming soon.

Related peptides

Other compounds indexed on Pepteligence that share research tags with Semax. Educational context only.

Selank

Tier 3
nootropicfocuscognitive

Safety

Common side effects

  • ·[insufficient evidence in research packet — no human clinical trials have characterized common side effects.]

Rare side effects

  • ·[insufficient evidence in research packet]
Safety notice — Serious / theoretical risks:
  • [insufficient evidence in research packet — serious adverse events in humans have not been studied.]

Contraindications

  • ·[insufficient evidence in research packet — no contraindications have been identified from the available sources.]

Community experiences

Community content — User-submitted experiences are self-reported and have not been verified. They do not constitute medical advice. Pepteligence aggregates community data under Section 230 protections.

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Semax — at a glance

PropertySemax—
Half-life——
Route——
Typical doseSee research context—
MechanismSemax (ACTH(4-7)PGP) is a synthetic analogue of the ACTH(4-10) fragment that exerts neuroprotective activity through several mechanistic pathways identified in animal and in vitro research. Animal studies indicate that Semax modulates differentially expressed genes associated with neuroprotection in ischemia-affected brain regions, and preliminary evidence from rat stroke models suggests that ACTH-like peptides including Semax compensate for disrupted brain gene expression profiles in the early post-stroke period. Animal studies also indicate that Semax modulates the expression pattern of immune genes in rat brain following experimental stroke. In a spinal cord injury model using male Sprague Dawley rats, animal studies indicate that ACTH4-10Pro8-Gly9-Pro10 (Semax) modulates anti-inflammatory cytokine expression, specifically upregulating IL-4, IL-10, and IL-13. Animal studies further indicate that Semax targets the μ opioid receptor gene Oprm1, promoting deubiquitination and contributing to functional recovery after spinal cord injury in female mice. At a neuronal level, mechanistic data in rat brain neurons point to Semax increasing the frequency of spontaneous intracellular calcium fluctuations in pyramidal neurons of the hippocampal CA1 field. Mechanistic data also suggest that synthetic corticotropins including Semax allosterically modulate the GABA-receptor system. In vitro evidence indicates that Semax acts as a copper chelator, inhibiting Cu(II)-catalyzed reactive oxygen species production and cytotoxicity of amyloid-beta through metal ion stripping and redox silencing, and in vitro studies further indicate that Semax affects copper-induced amyloid-beta aggregation and amyloid formation in artificial membrane models. All mechanistic pathways described here are derived from animal or in vitro data; human pharmacological confirmation is absent from the current evidence base.—
Evidence strengthanimalanecdotal
Primary goalnootropic—

Frequently asked questions

What is Semax?
Semax (ACTH(4-7)PGP) is a synthetic heptapeptide derived from the adrenocorticotropic hormone (ACTH) fragment, investigated primarily for neuroprotective, anti-inflammatory, and cognitive-enhancing properties in animal and in vitro research. No randomized controlled human clinical trials have been conducted. It is not FDA-approved.
How does Semax work?
Animal studies indicate that Semax modulates differentially expressed genes associated with neuroprotection in ischemia-affected brain regions. Preliminary evidence from animal and in vitro research suggests additional anti-inflammatory and potentially cognitive-enhancing pathways. No human mechanistic data from randomized controlled trials have validated these findings.
What is Semax used for?
Animal and in vitro research has investigated Semax for potential roles in neuroprotection, anti-inflammatory activity, and cognitive enhancement. No controlled human clinical trials have established safety or efficacy for any indication. It has been used in research contexts in Russia under a different regulatory framework.
Is Semax FDA-approved?
No. Semax is not FDA-approved for any indication. No randomized controlled human clinical trials have been conducted to establish its safety or efficacy profile.
What are common dosages of Semax?
No validated human clinical dosing data have been established for Semax in the current research literature. No approved dose or frequency is documented from controlled trials.
How is Semax administered?
No validated route of administration has been established from controlled human trial data for Semax. The research packet does not identify a confirmed route based on evidence meeting clinical standards.
What are common side effects of Semax?
No controlled human clinical trial data exist to characterize Semax's side-effect profile. Its safety in humans is not established from randomized trial methodology.
Are there safety concerns with Semax?
No contraindications have been identified from the available research literature for Semax. The absence of human safety data means no definitive conclusions about safety in any population can be drawn.
Is Semax related to ACTH?
Semax is derived from the ACTH(4-10) fragment — specifically residues 4–7 of ACTH (with Pro-Gly-Pro as a stabilizing extension). It is structurally related to ACTH but engineered for neuroprotective research rather than adrenocortical stimulation, and its studied mechanism differs from that of the full ACTH molecule.
Is Semax legal?
Semax is not FDA-approved and is not a scheduled controlled substance in the United States. Its regulatory status varies internationally — it has been used in Russia under a different framework. Legal status for possession and importation varies by jurisdiction. This is not legal advice.
Can Semax be combined with other compounds?
No evidence-supported combination protocols have been established for Semax in the current research literature. No stacking combinations with human-validated data were identified.
What does the research on Semax show overall?
The Semax research base consists entirely of animal and in vitro studies. No randomized controlled human clinical trials have been conducted to validate neuroprotective, anti-inflammatory, or cognitive effects in humans. Extrapolating preclinical findings to human outcomes is not warranted by current evidence.

References

  1. [1]

    Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.

    Liu Rongjie, Chen Yituo, Huang Haosheng et al.

    British journal of pharmacology · 2025 · PMID 40692165

    View on PubMed →
  2. [2]

    Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage.

    Filippenkov Ivan B, Shpetko Yana Yu, Ales Daria A et al.

    International journal of molecular sciences · 2025 · PMID 40650034

    View on PubMed →
  3. [3]

    Effect of ACTH4-10Pro8-Gly9-Pro10 on anti-inflammatory cytokine (IL-4, IL-10, IL-13) expression in acute spinal cord injury models (male Sprague Dawley rats).

    Asadullah Asadullah, Bajamal Abdul Hafid, Parenrengi Muhammad Arifin et al.

    F1000Research · 2023 · PMID 41179234

    View on PubMed →
  4. [4]

    The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease.

    Radchenko A I, Kuzubova E V, Apostol A A et al.

    Acta naturae · 2025 · PMID 41479572

    View on PubMed →
  5. [5]

    Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress.

    Inozemtseva Ludmila S, Yatsenko Ksenia A, Glazova Natalya Yu et al.

    European journal of pharmacology · 2024 · PMID 39442746

    View on PubMed →
  6. [6]

    Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing.

    Tomasello Marianna Flora, Di Rosa Maria Carmela, Naletova Irina et al.

    Bioinorganic chemistry and applications · 2025 · PMID 40496623

    View on PubMed →
  7. [7]

    Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models.

    Sciacca Michele F M, Naletova Irina, Giuffrida Maria Laura et al.

    ACS chemical neuroscience · 2022 · PMID 35080861

    View on PubMed →
  8. [8]

    ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke.

    Filippenkov Ivan B, Shpetko Yana Yu, Stavchansky Vasily V et al.

    Biomedicines · 2024 · PMID 39767736

    View on PubMed →
  9. [9]

    Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period.

    Filippenkov Ivan B, Remizova Julia A, Stavchansky Vasily V et al.

    Genes · 2023 · PMID 37510287

    View on PubMed →
  10. [10]

    The Effect of Peptide Semax, an ACTH(4-10) Analogue, on Intracellular Calcium Dynamics in Rat Brain Neurons.

    Kolbaev S N, Sharonova I N, Skrebitsky V G

    Bulletin of experimental biology and medicine · 2025 · PMID 41171324

    View on PubMed →
  11. [11]

    Synthetic corticotropins and the GABA-receptor system: Direct and delayed effects.

    Vyunova Tatiana V, Andreeva Ludmila A, Shevchenko Konstantin V et al.

    Chemical biology & drug design · 2023 · PMID 36828803

    View on PubMed →