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Neurological — ACTH Fragment AnalogResearch Use

Semax

Also known as: ACTH 4-10 analog · Heptapeptide Semax

MW

813.93 Da

Amino Acids

7 AA

Half-Life

3-5 minutes (rapid CNS uptake)

Route

Intranasal, SubQ

CAS

80714-61-0

Formula

C37H51N9O10S

Amino Acid Sequence

Met-Glu-His-Phe-Pro-Gly-Pro

Mechanism of Action

Semax is a synthetic heptapeptide analog of ACTH fragment 4-7 (Met-Glu-His-Phe) with Pro-Gly-Pro C-terminal extension. Despite being derived from ACTH, Semax does NOT activate the adrenal cortex — no cortisol elevation. The nootropic active region (positions 4-7) is distinct from the adrenal-stimulating region (positions 1-3).

BDNF/NGF UPREGULATION: Potently upregulates BDNF and NGF expression in hippocampus and cortex → enhanced neuroplasticity, learning, memory consolidation, and neuroprotection.

DOPAMINE/SEROTONIN MODULATION: Modulates dopaminergic and serotonergic neurotransmission, increasing attention, focus, and information processing speed without stimulant side effects.

NEUROPROTECTION: In ischemic stroke models, Semax reduces infarct volume by activating anti-apoptotic pathways and enhancing cerebral blood flow. This is the basis for its Russian approval in stroke recovery.

Approved in Russia and Ukraine for cognitive enhancement and stroke recovery. One of the most widely prescribed nootropic peptides in the former Soviet countries.

Dosing Protocol

Low Dose

███ – ███ mcg/day

Standard Dose

███ mcg/day

High Dose

███ – ███ mcg/day

Dosing protocols are for paid members

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Frequency

2–3x daily intranasal.

Half-Life

3-5 minutes (rapid CNS uptake)

Reconstitution Guide

Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.

Unlock reconstitution guide →

Clinical Warnings

Russian research program — limited Western replication.

May interfere with sleep at higher doses.

Not FDA approved.

Potential interaction with dopaminergic medications.

Quality concerns outside Russia/Ukraine.

Contraindications

Absolute

Pregnancy

Acute psychosis

Relative Cautions

Seizure disorders

Bipolar disorder

Hypertension

Side Effect Profile

Mild

  • Nasal dryness
  • Mild headache

Moderate

  • Irritability
  • Insomnia
  • Blood pressure fluctuation

Severe (Rare)

  • Psychomotor agitation in susceptible individuals

Synergistic Peptides

SelankBPC-157NAD+

Common Stacks

Selank

Research Status

APPROVED IN RUSSIA/UKRAINE. PMID 22411908 (Jain 2012): ACTH 4-7 analog neuroprotection and BDNF upregulation. PMID 9399231 (Ashmarin 1997): Stroke clinical data and Russian approval basis. Limited Western research.

Frequently Asked Questions

How does Semax work?

Semax is a synthetic heptapeptide analog of ACTH fragment 4-7 (Met-Glu-His-Phe) with Pro-Gly-Pro C-terminal extension. Despite being derived from ACTH, Semax does NOT activate the adrenal cortex — no cortisol elevation. The nootropic active region (positions 4-7) is distinct from the adrenal-stimulating region (positions 1-3). BDNF/NGF UPREGULATION: Potently upregulates BDNF and NGF expression in hippocampus and cortex → enhanced neuroplasticity, learning, memory consolidation, and neuroprotect

What is the standard dose of Semax?

Semax dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: 2–3x daily intranasal.

What is the half-life of Semax?

The half-life of Semax is 3-5 minutes (rapid CNS uptake). This determines optimal dosing frequency and timing.

Who should not use Semax?

Semax is absolutely contraindicated in: Pregnancy; Acute psychosis. Use with caution in: Seizure disorders; Bipolar disorder; Hypertension.

What are the side effects of Semax?

Common mild side effects include: Nasal dryness, Mild headache. Moderate effects: Irritability, Insomnia, Blood pressure fluctuation.

What peptides stack well with Semax?

Semax is commonly stacked with: Selank, BPC-157, NAD+.

How do you reconstitute Semax?

Semax is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.

How long should you cycle Semax?

Semax cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.

References & Citations

10 PubMed studies · 0 clinical trials

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, Turchan Agus et al.. F1000Research. 2023

PubMed: 41179234DOI ↗C — Research Article

Spinal cord injury (SCI) is a damage to the spinal cord caused mainly by trauma resulting in major motor, sensory and autonomic dysfunctions. Its final neurological outcome is determined by both prima

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

PubMed: 41171324DOI ↗C — Research Article

We studied the effects of Semax on spontaneous fluctuations of intracellular calcium ion concentration [Ca2+]i in pyramidal neurons on hippocampal slices and on proton-induced increase in [Ca2+]i in c

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, Stavchansky Vasily V et al.. International journal of molecular sciences. 2025

PubMed: 40650034DOI ↗C — Research Article

In the treatment of ischemic stroke, an innovative approach is the use of neuroprotective compounds. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such dru

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, Kamensky Andrey A et al.. European journal of pharmacology. 2024

PubMed: 39442746DOI ↗C — Research Article

Current antidepressant therapy shows substantial limitations, and there is an urgent need for the development of new treatment strategies for depression. Stressful events and hyperactivity of the hypo

Changes of Transcriptomic Activity in Rat Brain Cells under the Influence of Synthetic Adrenocorticotropic Hormone-Like Peptides.

Filippenkov Ivan B, Glazova Nataliya Y, Sebentsova Elena A, Stavchansky Vasily V et al.. Biochemistry. Biokhimiia. 2024

PubMed: 39418522DOI ↗C — Research Article

Synthetic peptides have a wide range of clinical effects. Of particular interest are peptides based on adrenocorticotropic hormone (ACTH) both as already used and as potential drugs for preventing con

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, Denisova Alina E et al.. Genes. 2023

PubMed: 37510287DOI ↗C — Research Article

Ischemic stroke is an acute local decrease in cerebral blood flow due to a thrombus or embolus. Of particular importance is the study of the genetic systems that determine the mechanisms underlying th

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

Vyunova Tatiana V, Andreeva Ludmila A, Shevchenko Konstantin V, Glazova Nataliya Yu et al.. Chemical biology & drug design. 2023

PubMed: 36828803DOI ↗C — Research Article

The central effectors of the stress system are greatly interconnected and include, among others, a large group of peptides derived from proopiomelanocortin. In addition to natural corticotropins, a nu

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, Attanasio Francesco. ACS chemical neuroscience. 2022

PubMed: 35080861DOI ↗C — Research Article

Alzheimer's disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal

Symptom Indications

Brain fogCognitive declineStroke recoveryADHDDepressionNeuroprotection

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This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.