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Smx2.8

Semax Research

Mostly mechanism / observational

12 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Semax studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from mixed-quality randomised trials published 2005–2025 with a typical study size of 52 participants.

Based on 12 studies · 1 RCT · 186 total participants

Confidence

Low confidence

By outcome

Stroke & neuroprotectionIn a Russian open 110-patient study intranasal Semax added to stroke rehabilitation raised plasma BDNF and improved functional recovery; preclinical work shows neurotrophin induction and neuronal protection · Over weeks of treatment (small studies)
Mostly mechanism / observational7 studies
Cognitive functionMarketed and used for memory and attention; a Russian open 110-patient study reported raised BDNF and improved functional recovery added to rehabilitation, though independent replication is sparse · Days to weeks (small studies)
Mostly mechanism / observational5 studies

Steady research

2 studies in the last 5 years

200520152025

1RCT2007

Serdiuk AV, Levitskiĭ GN, Miasoedov NF, Skvortsova VI · Zh Nevrol Psikhiatr Im S S Korsakova (2007)

No plain-language summary recorded for this citation — open the paper to read its abstract.

2Animal2025

In plain English: Semax promoted SCI functional recovery by targeting μ-opioid receptors, which regulated USP18 and, subsequently, deubiquitination of the fat mass and obesity-associated protein (FTO), suggesting its potential for SCI treatment.

Liu R, Chen Y, Huang H, Li X, Lv J, Jiang L, Jiang H, Wu C. · Br J Pharmacol (2025)

Mouse spinal-cord-injury (SCI) model plus PC12 neuroinflammation model — an independent (Chinese) group, not the originating Russian labs
Semax improved functional recovery (Basso scores, footprint, inclined-plane) and inhibited lysosomal-permeabilization-related pyroptosis by reducing oxidative stress
RNA-seq, network pharmacology and docking implicated the μ-opioid receptor and the deubiquitinase USP18 as targets/effectors

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3Animal2006

In plain English: These findings indicate that the cognitive effects exerted by Semax might be associated, at least in part, with increased BDNF protein levels in this brain region.

Dolotov OV, Karpenko EA, Seredenina TS, Inozemtseva LS, Levitskaya NG, Zolotarev YA. · J Neurochem (2006)

Rat study; intranasal Semax (50 and 250 microg/kg) rapidly increased BDNF levels in the basal forebrain after 3 h, but not in the cerebellum
Identified specific, reversible, calcium-dependent binding sites for tritiated Semax in basal-forebrain membranes (KD ~2.4 nM)
Links the proposed cognitive action to regional BDNF induction and a specific binding site

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4Animal2005

In plain English: Our results reveal the positive modulatory effect of Semax on the striatal serotonergic system and the ability of Semax to enhance both the striatal release of dopamine and locomotor behavior elicited by D-amphetamine.

Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. · Neurochem Res (2005)

Rodent neurochemistry study; Semax increased striatal 5-HIAA tissue content (+25%) and raised extracellular 5-HIAA up to 180% over 1-4 h
Semax alone did not change dopamine or its metabolites, but markedly enhanced amphetamine-evoked extracellular dopamine and locomotion
Implicates melanocortin-monoamine cross-talk in Semax's 'nootropic'/arousal effects

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5Animal2006

In plain English: We suggest that Semax affects cognitive brain functions by modulating the expression and the activation of the hippocampal BDNF/trkB system.

Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J. · Brain Res (2006)

Rat study; a single 50 microg/kg dose of Semax increased hippocampal BDNF protein (~1.4-fold) and trkB tyrosine phosphorylation (~1.6-fold)
Raised exon-III BDNF mRNA (~3-fold) and trkB mRNA (~2-fold) in the hippocampus
Semax-treated rats showed a distinct increase in conditioned avoidance reactions (a learning measure)

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6In Vitro2008

In plain English: We have shown that Semax may approximately 1.5-1.7 fold increase survival of cholinergic basal forebrain neurons in vitro.

Grivennikov IA, Dolotov OV, Zolotarev YA, Andreeva LA, Myasoedov NF, Leacher L, Black IB, Dreyfus CF. · Restor Neurol Neurosci (2008)

In-vitro study of rat basal-forebrain neuronal/glial cultures
Semax increased survival of cholinergic basal-forebrain neurons ~1.5-1.7 fold and stimulated choline acetyltransferase activity
Did not affect GABAergic neurons or glial proliferation

7Animal2010

In plain English: We have shown for the first time that both Semax and PGP activate the transcription of neurotrophins and their receptors in the cortex of rats subjected to pMCAO.

Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. · Cell Mol Neurobiol (2010)

Rat permanent middle-cerebral-artery-occlusion (pMCAO) stroke model; gene expression measured at 3, 24 and 72 h
Semax enhanced transcription of Bdnf, TrkC and TrkA at 3 h and Nt-3/Ngf later, selectively in ischemic cortex
The PGP fragment's effects were largely non-specific by comparison

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8In Vitro2007

In plain English: The neuroprotective effect of semax in cerebral ischemia/hypoxia can be due to improvement of mitochondrial resistance to 'calcium' stress.

Storozhevykh TP, Tukhbatova GR, Senilova YE, Pinelis VG, Andreeva LA, Myasoyedov NF. · Bull Exp Biol Med (2007)

In-vitro study in cultured cerebellar granule cells under glutamate excitotoxicity
Semax (100 microM) and its PGP fragment delayed calcium dysregulation and loss of mitochondrial potential
Improved neuronal survival by ~30% on average

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9Review2024

In plain English: The review of clinical studies indicates that MGHPPGP is clinically effective in the treatment of ischemic stroke both in the acute period of stroke and in the recovery period.

Spirin NN, Fedorov VN, Vdovichenko VP. · Zh Nevrol Psikhiatr Im S S Korsakova (2024)

Russian review of clinical studies of intranasal Semax (MGHPPGP) in ischemic stroke
Reports clinical efficacy in both the acute and recovery periods of stroke, framing the intranasal route as a way around the closed 'therapeutic window'
Reports efficacy across atherothrombotic and cardioembolic subtypes and both carotid and vertebrobasilar territories

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10Open-Labeln=110 · medium study2018

In plain English: Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance.

Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN. · Zh Nevrol Psikhiatr Im S S Korsakova (2018)

110 patients after ischemic stroke, divided into early/late rehabilitation groups with semax+ and semax- subgroups; standard regimen 6000 mcg/day intranasally in two 10-day courses
Semax raised and sustained plasma BDNF levels regardless of rehabilitation timing
Semax and high BDNF accelerated and improved final Barthel-index recovery, with a positive BDNF-Barthel correlation

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11Open-Labeln=52 · small study2020

In plain English: Post hoc analysis allowed us to define both general and specific effects of Selank and Semax on FC between the right amygdala and the right temporal cortex for the first time.

Panikratova YR, Lebedeva IS, Sokolov OY, Rumshiskaya AD, Kupriyanov DA, Kost NV, Myasoedov NF. · Dokl Biol Sci (2020)

Resting-state fMRI in 52 healthy participants, comparing Semax, Selank and placebo before and 5/20 min after injection
Examined whole-brain functional connectivity of amygdala and dorsolateral prefrontal cortex regions of interest
Found between-group and between-condition differences in connectivity between the right amygdala and right temporal cortex

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12Open-Labeln=24 · very small study2018

In plain English: A greater volume of the default mode network rostral (medial frontal cortex) subcomponent was detected in the Semax group in comparison with controls.

Lebedeva IS, Panikratova YR, Sokolov OY, Kupriyanov DA, Rumshiskaya AD, Kost NV, Myasoedov NF. · Bull Exp Biol Med (2018)

Resting-state fMRI in healthy volunteers (24 subjects), 3 scans before and 5/20 min after intranasal 1% Semax (14) or placebo (10)
Studied the topography of the default mode network
Found a greater volume of the rostral (medial frontal cortex) default-mode subcomponent in the Semax group

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View in Research Library

Semax Research

Mostly mechanism / observational

[The study of chronic partial denervation and quality of life in patients with motor neuron disease treated with semax].

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

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.

Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.

Effects of behaviorally active ACTH (4-10) analogue - Semax on rat basal forebrain cholinergic neurons.

Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia.

Effects of semax and its Pro-Gly-Pro fragment on calcium homeostasis of neurons and their survival under conditions of glutamate toxicity.

[Place of oligopeptide H-Met-Glu-His-Phe-Pro-Gly-Pro-OH in the therapy and rehabilitation of patients with ischemic stroke].

[The efficacy of semax in the treatment of patients at different stages of ischemic stroke].

Functional Connectomic Approach to Studying Selank and Semax Effects.

Effects of Semax on the Default Mode Network of the Brain.