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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)
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
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.
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
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)
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.
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
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
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
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
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