Semax — Peptide Protocol Wiki reference

Both ADHD and Rett syndrome involve dysfunction in pathways that Semax modulates (PMID: 16996699).

Semax: Neuroprotective ACTH Analog Guide | Peptide Protocol Wiki Skip to main content 🧬 Peptide Protocol Wiki Peptides Side Effects New Learn Directory Tools Blog News About ⌘K ⌘K 🌱 New to Peptides?

Start the 7-step beginner guide Peptides Side Effects New Directory Learn Tools Blog News About Semax 📋 Overview 🧬 Molecule 🔄 Similar ⚠️ Side Effects 💉 Dosing 🔬 Research 🚨 Risks 👥 Community 📊 Community Data Home Peptides Semax Cognitive Enhancement Brain & Neuroprotection approved Semax Also known as: ACTH(4-7)-PGP, Semax Peptide Compare with 2 peptide s Research compiled by Peptide Protocol Wiki 📅 Updated February 9, 2026 Citations Verified TL;DR Semax is a synthetic heptapeptide derived from the ACTH(4-7) fragment with a C-terminal Pro-Gly-Pro extension for metabolic stability.

It is approved in Russia for treatment of stroke, cognitive disorders, and optic nerve disease, and has been studied for neurotrophic factor upregulation including BDNF and NGF.

Unlike most peptides covered on this site, Semax has decades of clinical use in Russia, though it lacks FDA approval or EMA authorization.

Browse all cognitive peptides → Table of Contents 📌 TL;DR • Approved in Russia for stroke recovery and cognitive disorders • Upregulates BDNF and NGF expression in preclinical models • Does not affect adrenal cortex function despite ACTH origin • Demonstrated neuroprotective effects in isch

emic stroke models • Modulates dopaminergic and serotoninergic brain systems Community-Reported Side Effects Anecdotal ?

Neurotrophic Factor Upregulation # The most well-characterized mechanism is the upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression.

(2006) demonstrated that a single intranasal dose of Semax (50 mcg/kg) produces a 1.4-fold increase in BDNF protein levels and a 1.6-fold increase in trkB tyrosine phosphorylation in the rat hippocampus.

📋 Protocol Quick-Reference Cognitive enhancement, neuroprotection, and ischemic stroke treatment (approved in Russia) 💉 Dosing Amount 200-600 mcg per dose (0.1% solution) for nootropic use; 3-6 mg per dose (1% solution) for stroke Frequency 2-3 times daily Duration 10-14 day courses, repeated after 2-4 week break; 2-4 courses per year 💊 Administration Route Intranasal Schedule 2-3 times daily Timing Morning and early afternoon; avoid late evening administration as it may interfere with sleep 📅 Cycle Duration 10-14 day courses, repeated after 2-4 week break; 2-4 courses per year Rest Period 4 weeks off between cycles Repeatable Yes Course-based protocol with rest periods Preparation & Storage ✓ Ready-to-use — no reconstitution required Storage: Store lyophilized Semax at -20 degrees Celsius protected from light.

ealth baseline CMP When: Baseline Why: Liver and kidney function Fasting glucose When: Baseline Why: ~7% of diabetic patients report blood glucose elevation with Semax Thyroid panel When: Baseline Why: Semax is an ACTH fragment; rule out adrenal/thyroid dysfunction Cortisol (AM) When: Baseline Why: ACTH-derived peptide may influence HPA axis Fasting glucose When: End of 10-14 day course Why: Monitor for glucose elevation, especially in diabetics 💡 Key Considerations → 1% solution for acute stroke (medical supervision required) → Contraindication: Not approved by FDA/EMA; caution in diabetes due to potential glucose elevation; caution with hypertension; avoid in pregnancy Subscribe to unlock this content Get weekly peptide research summaries, new study alerts, and protocol updates — free.

Restore access No thanks, continue reading Related Reading Peptide Selank anxiolytic nootropic peptide Peptide Pinealon neuroprotective bioregulatory tripeptide Peptide Dsip peptide How Semax works at the cellular level Overview of Semax benefits and applications Scientific Details Molecular Formula C37H51N9O10S Molecular Weight 813.93 Da CAS Number 80714-61-0 Sequence Met-Glu-His-Phe-Pro-Gly-Pro What is Semax?

It is approved as a pharmaceutical product in Russia and several Commonwealth of Independent States (CIS) countries, where it is prescribed for ischemic stroke recovery, cognitive impairment, and optic nerve diseases.

However, it has never been submitted for regulatory approval in Western markets and remains an unapproved research chemical in the United States, European Union, and most other countries.

At therapeutic doses, Semax does not stimulate cortisol release, does not affect adrenal function, and does not produce the metabolic side effects associated with corticosteroid administration.

Mechanism of Action # Semax's mechanism of action is multifaceted and involves several converging pathways in the central nervous system.

At the mRNA level, exon III BDNF showed a 3-fold increase and trkB mRNA a 2-fold increase (PMID: 16996037).

(2010) showed that Semax induces multidirectional activation of NGF and BDNF gene expression across the hippocampus, frontal cortex, and retina, with the pattern varying by brain region and time after administration (PMID: 19662538).

The binding was associated with increased BDNF protein levels at doses of 50 and 250 mcg/kg (PMID: 16635254).

Dopaminergic and Serotoninergic Modulation # Eremin et al.

The peptide produced significant increases in serotonin metabolite levels in the striatum, with extracellular concentrations rising to 180% within 1-4 hours after administration.

This neurotransmitter modulation provides a neurochemical basis for Semax's reported nootropic effects, as both dopamine and serotonin systems are critically involved in attention, memory consolidation, and cognitive flexibility.

cts through gene expression modulation.

(2014) performed genome-wide transcriptional analysis showing that Semax affects the expression of 96 genes at 3 hours and 68 genes at 24 hours post-stroke.

The immune response was identified as the process most markedly affected, with immunoglobulin genes showing up to 15-fold increases in expression and chemokine genes substantially upregulated (PMID: 24661604).

Clinical Applications in Russia # Ischemic Stroke # Semax's primary approved indication in Russia is the treatment of acute ischemic stroke and stroke recovery.

(1999) demonstrated that Semax at doses of 100-150 mcg/kg displays angioprotective, antihypoxic, and neurotrophic activity.

The drug shifts neuromediatory balance toward anti-inflammatory agents (IL-10, TNF-alpha modulation) while reducing pro-inflammatory markers (IL-8, CRP) during acute ischemic stroke recovery (PMID: 10358912).

In Russian clinical practice, Semax is administered intranasally at a 1% concentration (3 mg per dose) for acute stroke, typically initiated within hours of symptom onset and continued for 5-14 days.

The standard nootropic formulation is a 0.1% intranasal solution (30 mcg per drop), used in treatment courses of 10-14 days.

The retina and optic nerve express neurotrophic factor receptors, and Semax's ability to upregulate BDNF and NGF in retinal tissue provides a mechanistic rationale for this application.

Formulations # Semax is commercially available in Russia in two primary formulations: Formulation Concentration Per Drop Primary Indication 0.1% nasal drops 1 mg/mL ~30 mcg Cognitive enhancement, nootropic 1% nasal drops 10 mg/mL ~300 mcg Ischemic stroke, neuroprotection Both formulations are administered as intranasal drops, taking advantage of the nasal mucosa's direct access to the central nervous system via the olfactory and trigeminal nerve pathways.

How Semax Differs from Other ACTH-Derived Peptides # Semax is distinct from other ACTH fragments and analogs in several important ways: Versus full ACTH : Semax lacks adrenocortical activity and does not stimulate cortisol production Versus ACTH(4-10) : The PGP extension dramatically improves metabolic stability Versus Selank : Selank is a tuftsin analog with anxiolytic properties; Semax is an ACTH analog with nootropic properties.

They act through different receptor systems Versus Cerebrolysin : Cerebrolysin is a mixture of peptide fragments from porcine brain; Semax is a single defined peptide with known sequence Evidence Assessment # The evidence base for Semax includes decades of Russian clinical use, numerous preclinical studies published in peer-reviewed journals, and a handful of clinical investigations.

However, the evidence has significant limitations from a Western regulatory perspective: Most clinical studies were conducted in Russia with limited publication in English-language journals No Phase 3 randomized controlled trials meeting Western regulatory standards have been conducted The available clinical data often lacks the methodological rigor expected by the FDA or EMA Post-marketing surveillance data from Russian use has not been compiled in Western-accessible formats Despite these limitations, the preclinical evidence for Semax's neurotrophic and neuroprotective mechanisms is robust and has been published in wel

Evidence Gaps # No FDA or EMA clinical trials have been conducted Head-to-head comparison with established nootropics not available Long-term safety data from controlled studies absent Optimal dosing for different indications not established by Western standards Mechanism of specific binding and receptor identification incomplete Effects on human neurotrophic factor levels not confirmed in controlled studies Whether benefits from Russian clinical use translate to Western clinical endpoints is unknown Key Research Findings # Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents , published in Neurochemical Research (Eremin KO et al., 2005; PMID: 16362768): The study showed serotonin metabolite increase to 180% in striatum within 1-4 hours Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain , published in Journal of Neurochemistry (Dolotov OV et al., 2006; PMID: 16635254): The study showed specific Semax binding with KD of 2.4 nM The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis , published in BMC Genomics (Medvedeva EV et al., 2014; PMID: 24661604): The study showed immunoglobulin genes up to 15-fold upregulated Comparison of the

temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action , published in Journal of Molecular Neuroscience (Shadrina M et al., 2010; PMID: 19662538): The study showed BDNF elevation in retina by 90 minutes Related Reading # Semax research studies and evidence Semax dosing protocols Semax side effects profile ARA-290 research guide Cerebrolysin research guide Stay current on Semax research We summarize new studies, safety updates, and dosing insights — delivered biweekly.

It is approved in Russia for treatment of stroke, cognitive disorders, and optic nerve disease, and has been studied for neurotrophic factor upregulation including BDNF and NGF.

Unlike most peptides covered on this site, Semax has decades of clinical use in Russia, though it lacks FDA approval or EMA authorization.

What are the benefits of Semax?