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Semax

Tier 2 · Preclinical
Also known as ACTH(4-7) analog · Heptapeptide

Human evidence includes small randomized and non-randomized Russian clinical studies in acute ischemic stroke (e.g., 100-patient RCT of 12 mg/day intranasal, placebo-controlled NIHSS/Rankin analyses) plus healthy-volunteer studies of memory/attention and fMRI/EEG effects. However, this evidence rests mainly on small, older Russian trials with limited methodological rigor; no large modern RCTs, systematic reviews, or meta-analyses exist, and much mechanistic/dosing detail derives from animal, in-vitro, and expert-opinion/anecdotal (tier 2-4) sources.

Half-life
Not recorded
Routes
Intranasal · Subcutaneous · Intraperitoneal (animal studies)
Goals
cognitive · longevity · immune support
Cost / mg
Not recorded

How it works

Semax is a lab-made short peptide (seven amino acids) based on a fragment of the natural hormone ACTH, with an added 'Pro-Gly-Pro' tail. It was designed to keep ACTH's brain-supporting and memory-enhancing effects while dropping its hormonal action, so unlike ACTH it does not push the adrenal glands to release cortisol. In animals it raises levels of brain growth factors (especially BDNF and NGF) and their TrkB receptor, and it nudges serotonin and dopamine signaling. After brain injury such as stroke, it appears to dial down inflammation and oxidative stress while turning on genes tied to nerve repair, new blood vessels, and neuron survival. In people it has mainly been studied for stroke recovery and for improving short-term memory and attention.

Overview

Overview

Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), developed in the 1980s at the Institute of Molecular Genetics in Moscow. It is a hybrid molecule combining a fragment of adrenocorticotropic hormone (ACTH) with a C-terminal Pro-Gly-Pro tripeptide. Sources describe the ACTH portion inconsistently — some as ACTH(4-7) and others as ACTH(4-10) — but the seven-amino-acid sequence itself is consistent across reports. It has a reported molecular weight of ~813.9 g/mol (formula C37H51N9O10S, CAS 80714-61-0), though one source lists differing values.

Semax was deliberately designed to retain the neurotropic/nootropic effects of ACTH while eliminating hormonal (corticotropic) activity and improving proteolytic stability. Consistent with this design goal, it does not stimulate adrenal cortisol secretion at therapeutic doses. It is typically produced by solid-phase peptide synthesis using Fmoc chemistry.

Regulatory Status and Uses

Semax is not FDA-approved in the United States. It is registered/approved in Russia (variously dated 1994 or 1996) and appears on the Russian List of Vital and Essential Drugs. In Russia it is used clinically for acute ischemic stroke, transient ischemic attack, dyscirculatory encephalopathy, Parkinson's disease, optic/ocular nerve disease, cognitive disorders of various origins, peptic ulcer disease, neurological deficits in newborns, and as a general nootropic agent. It is broadly positioned as a nootropic and neuroprotective agent, particularly in cerebrovascular and stress-related conditions.

Mechanism Highlights

  • Neurotrophins: Semax increases BDNF, NGF, and the TrkB receptor in the hippocampus, cortex, and ischemic brain tissue. A single intranasal 50 µg/kg dose produced measurable increases in BDNF protein, trkB phosphorylation, and BDNF/trkB mRNA in rat hippocampus, with BDNF/NGF elevations seen at 3-8 hours.
  • Monoamines: It activates serotonergic systems (raising striatal 5-HIAA) and positively modulates dopaminergic responses, potentiating amphetamine-evoked dopamine release and locomotion. Whether Semax alone raises dopamine turnover is contested between sources.
  • Opioid / enzymatic: It targets the μ-opioid receptor and, via its Pro-Gly-Pro motif, may act as a substrate/inhibitor of enkephalin-degrading enzymes. Recent preclinical work links a μ-opioid/USP18/FTO deubiquitination pathway to reduced pyroptosis and oxidative stress.
  • Ischemia transcriptomics: In rodent stroke models, Semax remodels gene expression in a time-dependent manner — early immune/interferon activation and, by 24 hours, suppression of inflammation-related genes with activation of neurotransmission-, neurogenesis-, and angiogenesis-related genes, alongside CREB upregulation and MMP-9/c-Fos/JNK downregulation.

Evidence Base

Animal studies show improved cognition, reduced infarct size, antidepressant- and anxiolytic-like effects, reduced amyloid inclusions in Alzheimer's model mice, and functional recovery after spinal cord injury. In humans, intranasal Semax has improved short-term memory and attention in healthy volunteers and altered resting-state fMRI/EEG activity. Several Russian acute-stroke studies — including a 100-patient randomized trial (12 mg/day intranasal for 5 days) and placebo-controlled analyses showing improved NIHSS, Rankin, and Rivermead outcomes — report accelerated neurological recovery and increased plasma BDNF.

Important limitation: Much of the human evidence comes from small, older Russian studies with limited methodological rigor (the largest stroke study was non-randomized), and there are no large modern RCTs, systematic reviews, or meta-analyses. A substantial portion of mechanistic and dosing detail derives from animal, in-vitro, or expert-opinion/anecdotal sources.

What the research shows

275 findings extracted from the 30 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 9 human trial findings, 15 human study findings, 22 animal findings, 7 expert opinion findings and 1 theoretical finding.

  • human trialSemax had some influence on the rate of restoration of damaged neurological functions in acute ischemic stroke1

  • human trialSemax increased the regress of general cerebral and focal neurological disorders, especially motor disorders1

  • human trialSemax effects were monitored using EEG with mapping and somatosensory evoked potentials1

  • human trialIn acute stroke patients receiving Semax, there was significant stroke severity reduction using NIHSS at 10-14 and 21 days in subgroups of severe and moderate stroke severity, and only at 21 days for mild strokes compared to placebo3

  • human trialAmong patients receiving Semax compared with placebo, Rankin scale outcomes at 21 days were better only in subgroups of severe and moderate stroke3

  • human trialSignificantly better Rivermead mobility index results were observed in patients receiving Semax in all subgroups compared with placebo3

  • human trialSemax 1% intranasal administration in acute stroke period leads to neurological impairment decrease, mobility and functional independence increase3

  • human trialIn a placebo-controlled study in healthy human volunteers, a single intranasal dose of semax improved performance on attention and short-term memory tasks27

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  • human trialIn a randomized trial of 100 patients, intranasal semax at 12 mg/day for 5 days accelerated neurological recovery compared to standard care in acute ischemic stroke27

  • human studySemax administration, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period4

  • human studyIn semax- subgroups high BDNF plasma levels were positively correlated with early rehabilitation4

  • human studyAdministration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index4

  • human studyThere was a positive correlation between BDNF plasma levels and Barthel score4

  • human studyThere was a correlation between early rehabilitation and motor performance improvement4

  • human studyThe correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation4

  • human studyEarly rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance in patients after ischemic stroke4

  • human studySemax displays nootropic (memory/attention-enhancing) and neuroprotective properties across animal and human studies5

  • human studyIn healthy volunteers, intranasal Semax improved operative memory5

  • human studyIn a pilot study in 24 healthy subjects, intranasal 1% semax solution (total dose 1.2 mg) increased resting fMRI signal in the default mode network rostral subcomponent relative to placebo20

  • human studyAnother study in healthy patients reported that semax (250-1000 ug/kg) improved attention and short-term memory and caused EEG changes similar to other neuroprotective drugs20

  • human studySemax improved neurological function in stroke patients when added to standard of care20

  • human studyIn 110 patients with stroke, treatment with semax (2 courses – 6000 µg/day for 10 days with 20-day interval) increased plasma BDNF levels and treated patients with high BDNF levels had improved timing of rehabilitation20

  • human studyIn a 110-patient non-randomized Russian clinical trial, Semax at 6,000 mcg/day intranasally in two 10-day courses separated by a 20-day interval elevated plasma BDNF and improved Barthel index and MRC motor-scale scores over ~5 months in post-stroke patients24

  • human studyAn early human EEG study by Koroleva, Meizerov, and colleagues, published in Bulletin of Experimental Biology and Medicine in 1996, established measurable CNS electrophysiological activity of Semax in humans24

  • animalPreclinical studies demonstrate effectiveness of Semax under various types of stress3

  • animalThe nootropic neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has proved efficient in the therapy of brain stroke6

  • animalSemax improved cognitive functions in mice as demonstrated by open field, novel object recognition, and Barnes maze tests7

  • animalSemax derivative improved cognitive functions in mice as demonstrated by open field, novel object recognition, and Barnes maze tests7

  • animalNon-hormonal ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides showed significant effects on the functions of the nervous system8

  • animalSemax exhibits neuroprotective properties and improves cognitive function9

  • animalSemax improved SCI functional recovery in an SCI mouse model9

  • animalNeuroprotective effect of Semax was observed at the histological level in rat brains at 24 h after tMCAO10

  • animalChronic treatment with Semax reversed or substantially attenuated CUS-induced anhedonia in rats11

  • animalSemax attenuated body weight gain suppression induced by chronic unpredictable stress in rats11

  • animalSemax attenuated adrenal hypertrophy induced by chronic unpredictable stress in rats11

  • animalSystemically administered Semax exerts antidepressant-like effects on anhedonia in a chronic unpredictable stress rat model11

  • animalSemax attenuates markers of chronic stress load in male rats11

  • animalNeonatal fluvoxamine exposure leads to impaired emotional response to stress and novelty in adolescent and young adult rats13

  • animalNeonatal fluvoxamine exposure causes delayed acquisition of food-motivated maze task in adolescent and young adult rats13

  • animalSemax administration reduced anxiety-like behaviour in rats exposed to fluvoxamine13

  • animalSemax improved learning abilities in rats exposed to fluvoxamine13

  • animalSemax, consisting of the ACTH fragment and the tripeptide Pro-Gly-Pro (PGP), effectively protects brain against ischemic stroke15

  • animalSemax-treated animals showed a distinct increase in the number of conditioned avoidance reactions17

  • animalSemax (Met-Glu-His-Phe-Pro-Gly-Pro) demonstrates nootropic activity18

  • animalCognitive effect duration is ~4–8 hours in animal models26

  • animalLiu et al. (2025) demonstrated in a preclinical study that semax promoted functional recovery after spinal cord injury (SCI) in female mice27

  • expert opinionSemax exhibits nootropic effects, stimulating learning, attention, and memory formation in animals and humans7

  • expert opinionThere is little evidence whether semax would improve cognition in healthy patients and no evidence for Alzheimer's disease20

  • expert opinionRussian clinical protocols demonstrate safety in courses lasting 10 to 30 days, with repeat cycles possible after rest periods of 1 to 3 months21

  • expert opinionClinical studies demonstrate Semax's efficacy in accelerated neurological recovery following ischemic stroke22

  • expert opinionSemax demonstrates reduced infarct size and secondary brain injury in stroke treatment22

  • expert opinionResearch indicates Semax provides significant benefits in accelerated recovery from mild to moderate traumatic brain injury22

  • expert opinionAvailable evidence consists of small Russian studies from the 1990s-2000s with limited methodological rigor, recent preclinical animal studies, no large-scale randomized controlled trials meeting contemporary standards, and no systematic reviews or meta-analyses in major medical journals25

  • theoreticalAc-Semax lacks in vivo pharmacological and clinical validation5

How it works

Based on 1 human trial finding, 2 human study findings, 76 animal findings, 16 in vitro findings, 26 expert opinion findings and 24 theoretical findings.

  • human trialSemax is a synthetic derivative of ACTH-4-101

  • human studySemax affects whole-brain resting-state functional connectivity in healthy participants2

  • human studySemax produces effects on functional connectivity between the right amygdala and the right temporal cortex2

  • animalSemax can block major pathogenic mechanisms of brain damage3

  • animalSemax stimulates endogenous protective mechanisms through increased neurotrophic factors in blood, including brain-derived neurotrophic factor (BDNF)3

  • animalSemax increases expression of neurotrophins (e.g. BDNF and TrkB) in hippocampus and ischemic brain tissue5

  • animalSemax modulates gene networks related to immune response, inflammation, DNA repair, neurotransmission, vascular function, calcium homeostasis and neurotrophic factors5

  • animalSemax activates serotonergic systems and positively modulates dopaminergic responses5

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  • animalIn rodents Semax enhances striatal 5-HIAA and potentiates D-amphetamine-evoked dopamine release and locomotion5

  • animalSemax targets the μ-opioid receptor (Oprm1), regulates USP18 and deubiquitination pathways, with downstream effects on lysosomal membrane permeabilization, oxidative stress and pyroptosis after spinal cord injury5

  • animalThe peptide predominantly enhanced the expression of genes related to the immune system6

  • animalThree hours after pMCAO, Semax influenced the expression of some genes that affect the activity of immune cells6

  • animal24 h after pMCAO, the action of Semax on [immune-related genes continues]6

  • animalSemax reduced the number of amyloid inclusions in the cortex and hippocampus of transgenic APPswe/PS1dE9/Blg mice brains7

  • animalSemax derivative reduced the number of amyloid inclusions in the cortex and hippocampus of transgenic APPswe/PS1dE9/Blg mice brains7

  • animalSemax and ACTH(6-9)PGP significantly reduced profile disturbances caused by ischemia for almost two-thousand differentially expressed genes in frontal cortex related to neurotransmitter and inflammatory response8

  • animalPeptides generated fewer differentially expressed genes in the striatum than in the frontal cortex8

  • animalBoth peptides tended to normalize the profile of disturbances caused by ischemia for hundreds of differentially expressed genes in the striatum8

  • animal152 genes showed an even more affected profile in the striatum under ACTH(6-9)PGP action, predominantly associated with inflammation8

  • animalAbout hundred genes were overlapped between both peptides in both tissues and were associated with neuroactive ligand-receptor interaction8

  • animalDifferential spatial regulation of the ischemia process in rat brain at transcriptome levels was discovered under peptides with different ACTH structures8

  • animalSemax inhibited LMP-related pyroptosis in SCI mice and neuroinflammation models by decreasing oxidative stress9

  • animalSemax regulated the ubiquitin specific protease USP189

  • animalSemax promoted SCI functional recovery by targeting μ-opioid receptors, which regulated USP18 and subsequently deubiquitination of FTO9

  • animalSemax significantly reduced expression distortions caused by ischemia for 1171 genes associated with immune and neurosignaling pathways at 24 h after tMCAO in rat brain10

  • animalSemax revealed neurogenesis-, angiogenesis-, protein kinase- and growth factor-related differential gene expression under ischemic conditions10

  • animalThe pattern of Semax action on the transcriptome depends on the time elapsed after tMCAO, with different transcriptomic signatures at 4.5 h versus 24 h post-stroke10

  • animalSemax increased hippocampal levels of BDNF in chronically stressed rats11

  • animalSemax enhanced the transcription of neurotrophins and their receptors in models of cerebral ischemia in rats12

  • animalSemax modulated the expression of genes involved in the immune response in rat cerebral ischemia models12

  • animalSemax suppressed the expression of inflammatory genes in the rat transient middle cerebral artery occlusion (tMCAO) model12

  • animalSemax activated the expression of neurotransmitter genes in the rat tMCAO model12

  • animalAt 24 h after tMCAO, Semax induced upregulation of active CREB in subcortical structures including the focus of ischemic damage12

  • animalSemax caused downregulation of MMP-9 in the adjacent frontoparietal cortex at 24 h after tMCAO12

  • animalSemax caused downregulation of c-Fos in the adjacent frontoparietal cortex at 24 h after tMCAO12

  • animalSemax caused downregulation of active JNK in both subcortical structures and frontoparietal cortex at 24 h after tMCAO12

  • animalSuppression of inflammatory and cell death processes and activation of recovery may contribute to the neuroprotective action of Semax12

  • animalSemax exerts marked nootropic and neuroprotective activities13

  • animalFluvoxamine exposure induces alterations in monoamine levels in brains of 1- and 2-month-old rats13

  • animalSemax normalized brain biogenic amine levels impaired by fluvoxamine exposure13

  • animalSemax suppressed the expression of genes related to inflammatory processes in rat brains at 24 h after transient middle cerebral artery occlusion (tMCAO)14

  • animalSemax activated the expression of genes related to neurotransmission in rat brains at 24 h after tMCAO14

  • animalIschaemia-reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes14

  • animalThe neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia-reperfusion conditions14

  • animalSemax enhances antigen presentation signaling pathway15

  • animalSemax intensifies the effect of ischemia on the interferon signaling pathways15

  • animalSemax affects the processes for synthesizing immunoglobulins15

  • animalSemax significantly increased expression of the gene encoding the immunoglobulin heavy chain15

  • animalSemax highly affects cytokine, stress response and ribosomal protein-encoding genes after occlusion15

  • animalPGP treatment of rats with ischemia attenuates the immune activity and suppresses neurotransmission in the CNS15

  • animalNeuroprotective mechanism of Semax is realized via the neuroimmune crosstalk15

  • animalAfter intranasal application, Semax exerts marked neuroprotective activities17

  • animalA single application of Semax results in a maximal 1.4-fold increase of BDNF protein levels in the rat hippocampus17

  • animalA single application of Semax results in a 1.6-fold increase of trkB tyrosine phosphorylation levels in the rat hippocampus17

  • animalA single application of Semax results in a 3-fold increase of exon III BDNF mRNA levels in the rat hippocampus17

  • animalA single application of Semax results in a 2-fold increase of trkB mRNA levels in the rat hippocampus17

  • animalSemax affects cognitive brain functions by modulating the expression and the activation of the hippocampal BDNF/trkB system17

  • animalMelanocortinergic and monoaminergic brain systems have close functional and anatomical links18

  • animalTissue content of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum was significantly increased (+25%) 2 h after Semax administration18

  • animalExtracellular striatal level of 5-HIAA gradually increased up to 180% within 1-4 h after Semax administration18

  • animalSemax alone failed to alter the tissue and extracellular concentrations of dopamine and its metabolites18

  • animalSemax injected 20 min prior to D-amphetamine dramatically enhanced the effects of the latter on the extracellular level of dopamine and on the locomotor activity of animals18

  • animalSemax has a positive modulatory effect on the striatal serotonergic system18

  • animalSemax enhances both the striatal release of dopamine and locomotor behavior elicited by D-amphetamine18

  • animalIntranasal semax was reported to bind in the rat basal forebrain and increase BDNF levels 3 hours but not 24 hours after administration20

  • animalIntranasal semax increased BDNF in the hippocampus20

  • animalIntranasal semax increased BDNF and NGF in the frontal cortex and hippocampus 8 hours after administration20

  • animalIntranasal semax increased serotonin but not dopamine levels20

  • animalIntranasal semax potentiated the stimulatory effects of d-amphetamine20

  • animalIn healthy rats, intranasal and intraperitoneal semax improved cognition (passive avoidance test) 15 minutes after treatment20

  • animalIn a rat model of photothrombosis, six daily treatments with semax (250 ug/kg) after injury reduced infarction size and improved performance on a passive avoidance task20

  • animalSemax reduced neurological damage and improved performance on a passive avoidance test in a model of cerebral ischemia caused by gravitation overload20

  • animalIntranasal administration of semax in rats produced a rapid increase in BDNF mRNA expression in the hippocampus and basal forebrain27

  • animalSemax increases expression of nerve growth factor (NGF) and the TrkB receptor, which mediates BDNF signaling27

  • animalStudies in rodents demonstrated increased dopamine and serotonin turnover in the striatum and nucleus accumbens following intranasal administration27

  • animalAnimal models of cerebral ischemia demonstrated that semax reduces hippocampal neuronal death and activates transcription of neurotrophic factors following ischemic injury27

  • animalSemax reduces oxidative stress markers, attenuates glutamate excitotoxicity, and promotes neuronal survival in models of incomplete global ischemia27

  • animalSemax regulated the ubiquitin-specific protease USP18 and the mu opioid receptor (Oprm1) was identified as a key semax target27

  • animalSemax inhibited lysosomal membrane permeabilization (LMP)-related pyroptosis and reduced oxidative stress and neuroinflammation, promoting SCI recovery through a mu opioid receptor/USP18/FTO deubiquitination pathway27

  • in vitroN-acetyl Semax-amide (Ac-Semax) exhibits altered metal-binding and redox properties, with reduced cytoprotective capacity under oxidative stress conditions5

  • in vitroSemax is a synthetic heptapeptide comprising the ACTH (4-7) fragment and a C-terminal Pro-Gly-Pro tripeptide9

  • in vitroSemax targets μ-opioid receptors9

  • in vitroSemax (ACTH(4-7)-Pro-Gly-Pro) is a noncorticotropic synthetic analog of the ACTH(4-10) fragment11

  • in vitroSemax (MEHFPGP) is a synthetic analogue of ACTH(4-10)13

  • in vitroSemax is a heptapeptide with sequence Met-Glu-His-Phe-Pro-Gly-Pro that encompasses sequence 4-7 of N-terminal domain of ACTH plus a C-terminal Pro-Gly-Pro tripeptide16

  • in vitroN-terminal amino group acetylation (Ac-Semax) modifies the ability of Semax to form complex species with Cu(II) ion16

  • in vitroAt physiological pH, Ac-Semax forms [CuLH] complex with distorted CuNO chromophore with weak apical interaction of methionine sulphur16

  • in vitroCu(II)-Semax complex exhibits CuN chromophore, differing from Ac-Semax complex16

  • in vitro[CuLH] has more positive formal redox potential than Cu(II)-Semax corresponding species16

  • in vitroAmino-free Semax forms redox-stable complex species unreactive against ascorbic acid, unlike acetylated form16

  • in vitroBoth Semax and Ac-Semax form Zn(II) complex species with comparable strength16

  • in vitroPeptide group acetylation does not affect Zn(II) influx in neuroblastoma cells16

  • in vitroPunctuate distribution of Zn(II) within cells suggests preferred subcellular localization that might explain zinc toxic effect16

  • in vitroBestatin-sensitive aminopeptidase cleaves first and second N-terminal residues Met and Glu from semax, producing relatively stable intermediates19

  • in vitroDegradation intermediates of semax have comparable areas under degradation/accumulation curves to intact peptide, implying they can contribute to effects of intact peptides19

  • expert opinionSemax is a protective protein derived from a fragment of adrenocorticotropic hormone (ACTH)3

  • expert opinionSemax is a heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) which is a derivative of ACTH that possesses ACTH's neurotrophic effects and lacks its hormonal activity20

  • expert opinionACTH fragments are believed to increase circulation of monoamines in the brain20

  • expert opinionSemax does not appear to cause traditional tolerance in the way stimulants do, though receptor sensitivity adjustments may occur with prolonged continuous use21

  • expert opinionTaking periodic breaks of 2 to 4 weeks between cycles allows neurotrophin receptor systems to normalize and maintains optimal response to the peptide21

  • expert opinionSemax operates by upregulating brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)21

  • expert opinionSemax is a synthetic heptapeptide consisting of the amino acid sequence: Methionine-Glutamate-Histidine-Phenylalanine-Proline-Glycine-Proline21

  • expert opinionSemax is a synthetic heptapeptide derived from the N-terminal fragment of adrenocorticotropic hormone (ACTH 4-10)22

  • expert opinionSemax demonstrates superior stability compared to native ACTH fragments through strategic amino acid modifications22

  • expert opinionSemax increases brain-derived neurotrophic factor (BDNF), which supports neuronal growth and protection23

  • expert opinionSemax modulates dopaminergic and serotonergic systems to enhance mood regulation and cognitive function23

  • expert opinionSemax improves cerebral blood flow, essential for brain recovery23

  • expert opinionSemax has antioxidant properties that protect neural cells from oxidative stress and inflammation23

  • expert opinionSemax binds to melanocortin receptors, likely as an antagonist or partial agonist23

  • expert opinionSemax inhibits enkephalinase enzymes, prolonging the effects of natural regulatory peptides23

  • expert opinionSemax is an analog of the ACTH(4-7) fragment extended with a C-terminal Pro-Gly-Pro sequence that stabilizes the molecule against enzymatic degradation24

  • expert opinionSemax is designed to retain the cognitive-modulating properties of ACTH fragments without the steroidal and adrenal effects of full-length ACTH24

  • expert opinionSemax binds melanocortin receptors and upregulates BDNF and NGF expression in the hippocampus and cortex24

  • expert opinionSemax is a synthetic ACTH(4-10) analog25

  • expert opinionSemax may increase BDNF plasma levels25

  • expert opinionSemax may reduce neuroinflammation markers (IL-10, TNF-α modulation)25

  • expert opinionSemax may inhibit amyloid-β aggregation in Alzheimer's models25

  • expert opinionSemax may modulate μ-opioid receptors and deubiquitination pathways25

  • expert opinionSemax is proposed to act by upregulating BDNF, inhibiting enkephalin-degrading enzymes, and modulating serotonergic and dopaminergic neurotransmission26

  • expert opinionSemax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro, corresponding to the ACTH(4-7) fragment with an added C-terminal Pro-Gly-Pro tripeptide designed to improve metabolic stability27

  • expert opinionThe C-terminal Pro-Gly-Pro motif of semax acts as a substrate and inhibitor of enkephalin-degrading enzymes (enkephalinases), which may prolong the action of endogenous opioid peptides27

  • theoreticalSemax is a synthetic heptapeptide analogue of ACTH(4-10)5

  • theoreticalSemax was designed to retain neurotropic, but not endocrine, actions of adrenocorticotropic hormone while improving proteolytic stability5

  • theoreticalSemax is non-corticotropic, shows no hormonal activity, yet preserves melanocortin-like neurotropic effects5

  • theoreticalSemax is a hybrid molecule carrying an adrenocorticotropic hormone fragment, ACTH(4–7), and the Pro-Gly-Pro tripeptide7

  • theoreticalSemax is a heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) that is an analog of the adrenocorticotropin fragment (4-10)17

  • theoreticalSemax influences key neurotransmitter systems through enhanced dopaminergic signaling improving motivation, executive function, and reward processing22

  • theoreticalSemax modulates serotonergic system supporting mood regulation and stress resilience22

  • theoreticalSemax enhances cholinergic system promoting memory formation, attention, and learning capacity22

  • theoreticalSemax contributes to GABA system balance reducing anxiety and cognitive clarity22

  • theoreticalSemax demonstrates upregulation of neuroprotective genes including brain-derived neurotrophic factor (BDNF)22

  • theoreticalSemax enhances expression of genes involved in neuronal survival and synaptic repair22

  • theoreticalSemax provides enhanced endothelial function and blood-brain barrier integrity22

  • theoreticalSemax improves cerebral blood flow and oxygen delivery to neural tissues22

  • theoreticalSemax reduces pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and inflammatory mediators22

  • theoreticalSemax has the amino acid sequence Met-Glu-His-Phe-Pro-Gly-Pro24

  • theoreticalSemax is a synthetic heptapeptide derivative of adrenocorticotropic hormone (ACTH) fragment 4-1028

  • theoreticalSemax modulates brain-derived neurotrophic factor (BDNF)28

  • theoreticalSemax enhances dopaminergic and serotonergic neurotransmission28

  • theoreticalSemax regulates oxidative stress pathways28

  • theoreticalSemax amino acid sequence is Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP)28

  • theoreticalHis-Phe dipeptide sequence is important for interaction with melanocortin receptors28

  • theoreticalN-terminal Met-Glu-His-Phe sequence is essential for nootropic effects and neurotrophic factor modulation28

  • theoreticalAlloviroidin demonstrates high affinity for F-actin as is characteristic of virotoxins and phallotoxins29

  • theoreticalThe linear heptapeptide favored a turn conformation, facilitating cyclization between Val and d-Thr29

Dosing

Based on 5 human trial findings, 11 expert opinion findings and 1 anecdotal finding.

  • human trialThe most effective daily dose was 12 mg for patients with strokes of moderate severity1

  • human trialThe most effective daily dose was 18 mg for patients with severe strokes1

  • human trialTreatment course duration was 5 days for moderate severity strokes1

  • human trialTreatment course duration was 10 days for severe strokes1

  • human trialSemax dosing: 1% intranasal, 12-18 mg/day for first 10-14 days3

  • expert opinionSemax is usually taken intranasally by dropper20

  • expert opinionInjectable Semax cycles typically run 4 to 8 weeks for cognitive enhancement, with some protocols extending to 12 weeks when using a cycling pattern like 6 weeks on and 2 weeks off21

  • expert opinionStandard daily doses range from 0.3 mg to 0.8 mg administered subcutaneously, with gradual titration recommended for new users21

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  • expert opinionFor nasal spray, start with 300 micrograms daily with a maintenance range of 300 to 1,000 micrograms23

  • expert opinionFor nasal spray, doses up to 3,000 micrograms may be appropriate for some patients23

  • expert opinionFor subcutaneous injections, start at 100 to 200 micrograms daily and maintain at 200 to 500 micrograms23

  • expert opinionFor subcutaneous injections, doses can go up to 1,000 micrograms if needed23

  • expert opinionTreatment duration is typically 10 to 14 days, but can be repeated based on individual response23

  • expert opinionSemax is delivered intranasally, typically as a 0.1% or 1% aqueous solution24

  • expert opinionRussian literature suggests intranasal administration at 12 mg/day (moderate severity) to 18 mg/day (severe stroke) for 5-10 days for acute ischemic stroke25

  • expert opinionRussian literature suggests intranasal administration at 0.015-0.050 mg/kg for cognitive enhancement25

  • anecdotalStandard dosing is 200–2,000 µg intranasal daily in Russian clinical practice26

How the body handles it

Based on 1 human study finding, 5 animal findings, 2 in vitro findings, 6 expert opinion findings and 3 theoretical findings.

  • human studySemax shows measurable effects on functional connectivity 5 and 20 minutes after injection2

  • animalModification to the C-terminal with Pro-Gly-Pro increased effects to 20-24 hours in animal models20

  • animalSemax plasma half-life is ~2–5 min in rat26

  • animalSemax has 12–24h functional effects after intranasal administration26

  • animalSemax Tmax (intranasal) is ~5–15 min based on animal data26

  • animalSemax demonstrates CNS penetration via olfactory route in animal models26

  • in vitroSemax is degraded in rat blood and serum, with about one third to one half of the serum degrading activity ascribed to bestatin-sensitive aminopeptidase19

  • in vitroSemax is more stable than ACTH(4-10) against the action of other enzymes involved in degradation19

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  • expert opinionA single administration initiates BDNF increases that peak around 8 hours post-dose and remain elevated for 24 hours or longer21

  • expert opinionSemax exhibits excellent CNS penetration via intranasal administration22

  • expert opinionThe peptide exhibits excellent water solubility and high intranasal bioavailability22

  • expert opinionSemax is metabolized primarily through peptidase activity and eliminated via renal excretion, with detectability in plasma for several hours post-administration22

  • expert opinionSemax is designed to cross the nasal mucosa and reach the brain through olfactory pathways24

  • expert opinionHalf-life is several minutes in plasma; active metabolites may persist longer27

  • theoreticalFull clearance (5 half-lives) is ~60–90 min estimated26

  • theoreticalC-terminal Pro-Gly-Pro tripeptide sequence significantly enhances metabolic stability and bioavailability compared to native ACTH fragment28

  • theoreticalPro-Gly-Pro sequence at C-terminus contributes to proteolytic resistance by creating steric hindrance against peptidase attack28

Safety and side effects

Based on 2 animal findings, 1 in vitro finding and 9 expert opinion findings.

  • animalPreclinical studies demonstrate a broad therapeutic window and low toxicity, with minimal adverse effects reported in clinical settings5

  • animalUnlike ACTH, semax does not stimulate adrenal cortisol secretion at therapeutic doses27

  • in vitroSemax acetylation did not protect from Cu(II) induced toxicity on SH-SY5Y neuroblastoma cell line, demonstrating crucial role of free NH-terminus in cell protection16

  • expert opinionSemax does not exhibit any hormonal activity7

  • expert opinionLittle human evidence exists for potential side effects20

  • expert opinionSemax appears on the Russian List of Vital and Essential Drugs21

  • expert opinionSome patients might experience mild nasal irritation, headaches, restlessness, or slight anticoagulant effects23

  • expert opinionUse caution in patients with severe psychiatric disorders, particularly bipolar disorder23

Show the remaining 4

  • expert opinionSemax is not recommended for pregnant or breastfeeding women due to limited safety data23

  • expert opinionSemax is not approved by the FDA for use in the United States25

  • expert opinionRussian studies report minor side effects and good tolerability25

  • expert opinionNo systematic adverse event reporting by Western standards, unknown drug interactions, no long-term safety data, potential contamination or quality control issues with non-FDA-regulated sources25

What people use it for

Based on 1 human study finding, 3 animal findings, 12 expert opinion findings, 1 anecdotal finding and 3 theoretical findings.

  • human studySemax is a nootropic peptide2

  • animalSemax (ACTH(4-7)PGP) serves as a neuroprotective agent for stroke therapy based on ACTH10

  • animalSemax can prevent behavioural deficits caused by altered 5-HT levels during development13

  • animalAfter intranasal application, Semax has profound effects on learning17

  • expert opinionSemax has progressed from basic research to clinical use as a nootropic and neuroprotective agent, especially in cerebrovascular and stress-related conditions5

  • expert opinionSemax is included in the Russian List of 'Vital and Essential Drugs for Medical Application'7

  • expert opinionSemax is used to treat neurological pathologies and stress conditions7

  • expert opinionACTH(4-10) analogs like Semax may have therapeutic potential for treatment and prevention of depression and stress-related pathologies11

Show the remaining 12

  • expert opinionSemax is a synthetic melanocortin derivative (ACTHPGP) that has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation14

  • expert opinionSemax is used in Russia for stroke, dyscirculatory encephalopathy, Parkinson's, ocular nerve atrophy, and for newborns with neurological deficits20

  • expert opinionSemax holds approval in Russia for medical conditions including ischemic stroke, transient ischemic attack, optic nerve disease, and cognitive disorders21

  • expert opinionSemax (Met-Glu-His-Phe-Pro-Gly-Pro) engineered for neuroprotective and cognitive enhancement applications22

  • expert opinionSemax supports memory improvement, anxiety management, and recovery from neurological conditions23

  • expert opinionSemax is a synthetic heptapeptide analog of ACTH(4-7) registered in Russia since 1994 for cerebrovascular indications24

  • expert opinionSemax has been studied primarily in Russian medical literature for ischemic stroke and cognitive enhancement25

  • expert opinionIn Russia, semax is approved as a pharmaceutical product and is available as a 0.1% and 1% intranasal solution with approved indications including treatment of acute ischemic stroke, cognitive disorders of various origin, and peptic ulcer disease27

  • anecdotalSemax was approved in Russia in 1996 and is used clinically for stroke rehabilitation, cognitive impairment, optic nerve disease, and as a general nootropic agent26

  • theoreticalSemax is a synthetic melanocortin derivative used in the treatment of ischemic stroke12

  • theoreticalAc-Semax proposed for use as ionophore in antibody drug conjugates to produce dysmetallostasis in tumor cells16

  • theoreticalSemax demonstrates significant nootropic, neuroprotective, and neurorestorative properties28

Other findings

Based on 5 expert opinion findings and 5 theoretical findings.

  • expert opinionSemax is a synthetic heptapeptide derived from ACTH with sequence Met-Glu-His-Phe-Pro-Gly-Pro23

  • expert opinionSemax is not FDA-approved in the United States24

  • expert opinionSemax was developed in the 1980s at the Institute of Molecular Genetics in Moscow24

  • expert opinionNo formal human pharmacokinetic study has been published in PubMed-indexed English-language peer-reviewed literature as of May 202626

  • expert opinionSemax is not FDA-approved in the United States26

  • theoreticalSemax contains the Met-Glu-His-Phe-Pro-Gly-Pro sequence7

  • theoreticalSemax is synthesized using solid-phase peptide synthesis (SPPS) with Fmoc chemistry28

  • theoreticalAlloviroidin is a cyclic heptapeptide produced by several species of Amanita mushrooms29

Show the remaining 2

  • theoreticalAlloviroidin was synthesized via a [3 + 4] fragment condensation29

  • theoreticalGlobal deprotection and HPLC purification afforded alloviroidin with NMR spectra in excellent agreement with the natural product29

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Limited evidence

Human evidence relies mainly on small, older Russian studies lacking modern rigor.

What is the appropriate dosing, safety, and efficacy of the synthetic peptide Semax for neurological conditions? states available evidence consists of small Russian studies from the 1990s-2000s with limited methodological rigor, no large-scale RCTs meeting contemporary standards, and no systematic reviews or meta-analyses in major medical journals. Semax — Cognitive Vitality For Researchers notes there is little evidence for cognitive improvement in healthy patients and no evidence for Alzheimer's disease. The larger stroke study ([The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. - Abstract - Europe PMC, Superpower) was non-randomized.

Contested

Sources disagree on Semax's plasma half-life.

Semax Half-Life: Minutes Intranasal (estimated) — Pharmacokinetics & Evidence Review | Halflife Labs reports a plasma half-life of ~2-5 minutes in rat; Semax: Research Evidence & Safety Profile | PeptideInsight says several minutes in plasma with longer-lasting active metabolites; Semax Peptide | Focus & Brain Support estimates approximately 1-2 hours for plasma elimination. Semax — Cognitive Vitality For Researchers and Semax Half-Life: Minutes Intranasal (estimated) — Pharmacokinetics & Evidence Review | Halflife Labs also cite 12-24h functional effects distinct from plasma half-life.

Contested

Sources label Semax's parent ACTH fragment inconsistently — some say ACTH(4-7), others say ACTH(4-10).

The amino-acid sequence itself, Met-Glu-His-Phe-Pro-Gly-Pro, is reported identically everywhere. What differs is the shorthand for its ACTH origin. Precise descriptions call Semax the ACTH(4-7) fragment extended with a C-terminal Pro-Gly-Pro tripeptide added for proteolytic stability (Semax: Research Evidence & Safety Profile | PeptideInsight; Superpower; Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice). Other sources call it simply a synthetic analog or derivative of ACTH(4-10) (Semax and N Acetyl Semax-Amide: discovery, actions, safety, animal data, and development; [Effectiveness of semax in acute period of hemispheric ischemic stroke]; Semax Peptide | Focus & Brain Support; What is the appropriate dosing, safety, and efficacy of the synthetic peptide Semax for neurological conditions?; Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats). One report uses both forms together, naming the ACTH(4-7)-Pro-Gly-Pro structure while calling it an ACTH(4-10) analog (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).

Limited evidence

Much mechanistic and dosing detail comes from low-tier or theoretical/anecdotal sources.

Claims about neurotransmitter system effects, blood flow, injectable dosing regimens and cycling are largely from tier 3-4 vendor/expert-opinion sources (Semax Half-Life: Minutes Intranasal (estimated) — Pharmacokinetics & Evidence Review | Halflife Labs, Semax Peptide | Focus & Brain Support, Semax — Molecular Specifications & Research Monograph | Peptide Biologix, Semax: The Ultimate Guide to Cognitive Enhancement and Neuroprotection, Semax Cycle Length: How Long Can You Safely Run It?) rather than peer-reviewed clinical trials, and some are labeled theoretical.

Single source

Enzyme degradation pathway detail comes from a single in vitro study.

The specific finding that a bestatin-sensitive aminopeptidase accounts for one third to one half of serum degradation and cleaves N-terminal Met and Glu is reported only in N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes. (in vitro rat blood/serum).

Limited evidence

Spinal cord injury μ-opioid mechanism is based on recent preclinical animal work only.

The USP18/FTO/μ-opioid receptor pyroptosis pathway for SCI recovery derives from preclinical mouse studies (Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice., Semax: Research Evidence & Safety Profile | PeptideInsight) and Ac-Semax metal-binding claims are in vitro (Semax and N Acetyl Semax-Amide: discovery, actions, safety, animal data, and development, Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties.); Ac-Semax specifically lacks in vivo and clinical validation.

Contested

The preclinical BDNF findings for intranasal Semax come from separate rat studies that each measured a different brain region at a different time, rather than one consistent result.

According to the Cognitive Vitality review of Semax, three distinct rat studies reported effects on neurotrophic factors: in the basal forebrain, intranasal semax bound and raised BDNF 3 hours after administration but not at 24 hours (Dolotov et al, 2006); a separate study reported increased BDNF in the hippocampus (Dolotov et al, 2003); and another reported increased BDNF and NGF in the frontal cortex and hippocampus 8 hours after administration (Shadrina et al, 2010). The 8-hour timepoint is tied only to the frontal cortex and hippocampus, and no 8-hour measurement in the basal forebrain is described—so the timepoints and regions do not line up into a single coherent finding.

Contested

Semax's JNK-lowering effect in a rat stroke model appeared throughout the injured brain, not only in one cortical region.

In the rat transient middle cerebral artery occlusion study reported in "Brain Protein Expression Profile Confirms the Protective Effect of the ACTHPGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion," protein expression measured 24 h after occlusion showed Semax associated with upregulation of active CREB in subcortical structures, downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex, and downregulation of active JNK in both the subcortical structures and the frontoparietal cortex. The reduction in active JNK was seen in both tissues, not confined to the frontoparietal cortex.

Contested

The favorable safety picture rests on old, small studies, and the tolerability data have never been assessed by contemporary standards.

One review ("Semax and N-Acetyl-Semax-Amide: discovery, actions, safety, animal data, and development") describes a broad therapeutic window, low toxicity, and minimal adverse effects reported in clinical settings. A clinical assessment ("What is the appropriate dosing, safety, and efficacy of the synthetic peptide Semax for neurological conditions?") frames the same tolerability reports very differently: the available evidence consists entirely of small Russian studies from the 1990s-2000s with limited methodological rigor, with no large-scale randomized controlled trials meeting contemporary standards. That assessment notes the Russian studies report minor side effects and good tolerability but stresses there is no systematic adverse event reporting by Western standards, unknown drug interactions, and no long-term safety data. So the reassuring safety language reflects the limits of the underlying studies rather than a safety profile confirmed by modern methods.

What you may have heard

Cognitive-enhancement range '0.015-0.050 mg/kg' vs 'clinical studies used 250-1000 µg/kg' differ by ~5-20x and are prese…

0.050 mg/kg = 50 µg/kg, yet the second figure (250-1000 µg/kg) is 5-20x higher. At 70 kg, 250-1000 µg/kg = ~17.5-70 mg, which exceeds the stated acute-stroke doses (12-18 mg/day) — implausible that cognitive enhancement would use more drug than severe stroke. This looks like a unit/scale error or conflation of rodent per-kg dosing with human dosing that should be reconciled.

Inconsistency

A meta-analysis of Semax in acute stroke does exist, but it pools only three small Russian trials and its own authors call for a proper controlled trial.

One assessment describes the evidence as having "no systematic reviews or meta-analyses in major medical journals," alongside only small Russian studies from the 1990s-2000s and preclinical work. That qualifier matters: the meta-analysis 'Meta-analysis: Semax effectiveness in the acute period of stroke' does exist, but it was published in the Russian-language Bulletin of Rehabilitation Medicine and pools only 3 studies (n=181) out of 8 candidates (n=654), all drawn from the same domestic literature. The NIHSS, Rankin and Rivermead efficacy signals rest entirely on these three trials, and the meta-analysis itself concludes that a multicenter, double-blind, placebo-controlled study is still needed and that a standard study design is necessary for inclusion in future analyses.

What you may have heard

'μ-opioid receptor (Oprm1)' listed as a primary receptor target based essentially on one preclinical gene-expression stu…

Claim 15/34 describe Semax regulating the Oprm1 gene with USP18/FTO deubiquitination signaling in a single SCI mouse study (Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.). That is transcriptional/gene-targeting evidence, not demonstrated direct receptor binding/agonism. Listing μ-opioid receptor as a headline receptor target (and first in the list) overstates a single-source, recent preclinical finding.

What you may have heard

Semax's sequence is precisely the ACTH(4-7) fragment followed by a synthetic Pro-Gly-Pro tripeptide, yet reference sources label it inconsistently as an "ACTH(4-7)" or an "ACTH(4-10)" analog.

The sequence Met-Glu-His-Phe-Pro-Gly-Pro consists of the four N-terminal ACTH residues 4-7 (Met-Glu-His-Phe) joined to a synthetic C-terminal Pro-Gly-Pro tripeptide, rather than to native ACTH residues 8-10. Reference sources describe it both ways: several call it a hybrid or analogue of ACTH(4-7) plus Pro-Gly-Pro — the Acta Naturae Alzheimer's-model study states it "is a hybrid molecule carrying an adrenocorticotropic hormone fragment, ACTH(4–7), and the Pro-Gly-Pro tripeptide," the Peptide Biologix monograph derives the active core from ACTH(4-7), and a copper/zinc coordination study notes it "encompasses the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone and a C-terminal Pro-Gly-Pro tripeptide" — while others, such as the HVM Bioflux mini-review, call it a "heptapeptide analogue of ACTH(4-10)." The seven-residue peptide is modeled on the 4-10 region with its final three residues replaced by Pro-Gly-Pro, so ACTH(4-7)-Pro-Gly-Pro is the more exact structural descriptor.

What you may have heard

'High intranasal bioavailability' asserted for a heptapeptide from expert-opinion sources.

Peptides typically have low absolute intranasal bioavailability; nose-to-brain delivery does not equate to high systemic bioavailability. The claim rests on tier 3 expert-opinion sources (Semax Half-Life: Minutes Intranasal (estimated) — Pharmacokinetics & Evidence Review | Halflife Labs, Semax Peptide | Focus & Brain Support, Superpower) without PK data (and the profile notes no human PK study exists), so 'high' should be scrutinized.

What you may have heard

A '100-patient randomized trial (12 mg/day)' is asserted, but this rests on tier-3 Semax: Research Evidence & Safety Profile | PeptideInsight while the detailed larger strok…

The 'randomized' descriptor for the 100-patient trial comes only from a tier-3 vendor/review source (Semax: Research Evidence & Safety Profile | PeptideInsight); the tier-1 primary stroke sources describe non-randomized designs. The randomization claim should be verified against a primary source before being presented as an RCT.

Other

A 'slight anticoagulant effect' is named as a side effect, yet no caution follows about bleeding risk in stroke patients who may already be on blood-thinning drugs.

The overview 'Semax: The Ultimate Guide to Cognitive Enhancement and Neuroprotection' lists 'slight anticoagulant effects' among possible side effects and promotes Semax for ischemic stroke and brain-injury recovery—a population frequently taking antiplatelet or anticoagulant medication. Despite naming this effect, it offers no accompanying caution about bleeding risk or combined use with other blood-thinning agents. The only safety warnings given concern severe psychiatric disorders and pregnancy or breastfeeding.

What you may have heard

Semax is often presented as a proven stroke and cognitive drug, but the human evidence behind that reputation is small, old, and methodologically weak.

Semax is approved and widely used in Russia for stroke and cognitive conditions, which can give the impression of strong clinical backing. In reality the human evidence comes largely from small, older Russian trials — for example a 1997 study of 30 Semax-treated patients against 80 controls that was not randomized, and a 110-patient study that was also non-randomized and not placebo-controlled. A 2018 meta-analysis of the Russian literature found only three studies (181 patients total) rigorous enough to pool, found no human clinical trials in English-language journals, and found no Semax trials registered on clinicaltrials.gov. No large modern randomized controlled trials meeting contemporary standards exist. So the widespread positioning of Semax as an established neuroprotective therapy overstates what the published human evidence actually supports.

Contested

How long semax lingers in the blood is unsettled: most sources put it at only minutes, one puts it at one to two hours, and there is no human measurement to settle it.

The short estimate is not a measured human value. The Halflife Labs review reports roughly 2–5 minutes plasma half-life in rat, explicitly derived from animal data and the rapid proteolytic breakdown of heptapeptides, and notes no formal human pharmacokinetic study has been published; PeptideInsight similarly gives 'several minutes in plasma.' In contrast, Paragon Sports Medicine states a plasma elimination half-life of approximately 1–2 hours with detectability for several hours. A rat blood study, 'N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes,' found that degradation intermediates accumulate to a degree comparable with the intact peptide and may themselves contribute to its effects, so active metabolites may persist longer than the parent compound.

Using it with other compounds

Check a stack
  • SS-31Complementary

    No documented conflict

    SS-31 protects neurons by stabilizing mitochondria and reducing ROS, while Semax protects them through neurotrophin (BDNF/TrkB) signaling. The mitochondrial-protection plus neurotrophic-signaling combination targets different arms of neuroprotection, making them potentially complementary.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms explicitly support the claimed shared dimensions. Semax directly targets BDNF/NGF-TrkB neurotrophin signaling and produces anti-inflammatory effects through NF-kB modulation and interferon signaling. SS-31 explicitly lists BDNF synaptic signaling and inflammation/pyroptosis modulation in its pathways, plus anti-inflammatory in approved tags. The explanation correctly identifies that they operate through distinct mechanistic routes (Semax via neurotrophin signaling and dopaminergic/serotonergic modulation; SS-31 via mitochondrial stabilization and ROS reduction) that converge on shared outcomes (neuroprotection, anti-inflammation, BDNF signaling). This represents genuine complementarity—different upstream mechanisms producing overlapping protective effects—which is well-justified by the provided mechanism material.

    Shares anti inflammatory · BDNF signaling

  • BremelanotideStack with caution

    Worth caution

    Both peptides are derived from the melanocortin/proopiomelanocortin family (bremelanotide is an alpha-MSH analog, Semax is an ACTH(4-10) fragment). Bremelanotide is a melanocortin receptor AGONIST, while Semax is reported to act as a melanocortin receptor antagonist/partial agonist. Running them together could theoretically blunt bremelanotide's melanocortin signaling. They also both touch dopaminergic and serotonergic tone centrally.

    Tier 4Theoretical — not established

    Timing If used together, separate dosing and watch for reduced bremelanotide response; Semax's melanocortin antagonism is proposed, not confirmed.

  • SelankComplementary

    May be complementary

    Selank and Semax are sister Russian regulatory peptides that both raise BDNF/NGF and both inhibit enkephalinase (extending your own opioid peptides), yet they push in different directions: Selank is calming/anxiolytic while Semax is stimulating and pro-attention. Stacked, one tends to smooth out the over-activation of the other, which is why they are a widely used nootropic pairing.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    The mechanism descriptions clearly establish all three claimed shared dimensions: (1) dopaminergic_system—both peptides explicitly modulate serotonergic and dopaminergic pathways; (2) anti_inflammatory—both are tagged anti_inflammatory and target immune/cytokine signaling (Selank via Th1-Th2 and interferon, Semax via interferon and antigen-presentation); (3) BDNF_signaling—both are tagged BDNF_signaling and upregulate BDNF/NGF (Selank via BDNF/NGF signaling, Semax via BDNF/NGF-TrkB neurotrophin signaling). The proposed complementarity is also mechanistically justified: Selank targets GABA-A (allosteric, anxiolytic) and 5-HT1A/2A (calming), while Semax targets TrkB and melanocortin receptors with attention/stimulation effects. Both inhibit enkephalinase, supporting the shared opioid-peptide extension claim. The sister-peptide pairing and opposing functional profiles (calming vs. stimulating) while sharing core neurotrophin and immune pathways align with the complementary relationship type.

    Timing Often dosed together in the daytime; if Semax feels over-stimulating, take Selank alongside or shortly after.

    Shares dopaminergic system · anti inflammatory · BDNF signaling

  • KPVComplementary

    No documented conflict

    KPV is the C-terminal tripeptide of alpha-MSH (a melanocortin peptide) and Semax is an ACTH-derived melanocortin-family fragment; both exert anti-inflammatory effects and interact with the MMP-9 pathway. They act through different routes (KPV largely intracellular NF-kB suppression, Semax via neuro-immune modulation) but converge on dampening inflammation, making them plausibly complementary for anti-inflammatory goals.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    The proposed relationship lacks support from the mechanism descriptions. While both peptides show anti-inflammatory effects and MMP-9 involvement, the explanation falsely characterizes their melanocortin family status and receptor interactions. Semax targets TrkB and μ-opioid receptors with proposed melanocortin antagonism/partial agonism, whereas KPV's melanocortin-1 receptor binding is explicitly 'contested/minority reports' and most sources show independence from melanocortin receptors. The mechanisms do not establish a shared 'melanocortin-family' basis. Additionally, no 'shared dimensions' are claimed, yet the explanation asserts convergence on inflammation suppression—but this convergence is not explicitly supported by the provided mechanism material; it describes different pathways (neuro-immune modulation vs. intracellular NF-kB) without demonstrating mechanistic complementarity or synergy. The relationship is plausible in principle but not justified by the given mechanism descriptions alone.
  • EpithalonComplementary

    No documented conflict

    Semax drives BDNF/NGF neurotrophin signaling for cognitive and neuroprotective effects, a mechanism distinct from Epithalon's antioxidant/senescence and circadian actions. The two hit neurogenesis and brain protection through separate pathways and may be complementary.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms explicitly support neurogenesis as a shared dimension through distinct pathways: Epithalon lists 'neurogenesis' as an approved tag and describes 'neuroprotective and neurogenic effects' via antioxidant/senescence pathways and circadian regulation; Semax lists 'neurogenesis' as an approved tag and achieves neuroprotection through BDNF/NGF-TrkB neurotrophin signaling. The proposed relationship correctly identifies that they target neurogenesis through mechanistically separate pathways (Epithalon via telomerase/senescence/circadian mechanisms; Semax via BDNF/TrkB signaling), making them complementary rather than redundant. This aligns with the mechanism descriptions provided.

    Shares neurogenesis

  • DSIPComplementary

    Worth caution

    Both peptides engage the endogenous enkephalin/opioid system — DSIP releases Met-enkephalin while Semax inhibits enkephalin-degrading enzymes and acts at the μ-opioid receptor — and both report neuroprotective/antioxidant effects. Their upstream mechanisms differ, so together they could reinforce enkephalinergic and neuroprotective signaling, though Semax is stimulating/nootropic and DSIP is sedating.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    While both peptides have documented effects on enkephalinergic signaling and neuroprotection, the proposed relationship claims they are 'complementary' but provides no mechanistic basis for how their different enkephalin-system actions would synergize. DSIP releases Met-enkephalin via calcium-dependent mechanisms (proposed via DOR activation), while Semax inhibits enkephalinase degradation—these are mechanistically distinct pathways that do not clearly establish complementarity. The explanation acknowledges their 'upstream mechanisms differ' but offers only a speculative assertion ('could reinforce') without mechanistic justification from the provided descriptions. The contrast between DSIP's sedating and Semax's stimulating profiles actually suggests potential opposition rather than complementarity. The shared neuroprotective/antioxidant effects are both documented but are attributed to different pathways (DSIP: antioxidant enzyme upregulation; Semax: BDNF/TrkB/CREB signaling, MMP-9/JNK modulation) and do not constitute a clear shared dimension. The proposed relationship lacks sufficient mechanistic grounding in the provided material.

    Timing Semax is activating and best used earlier in the day; DSIP is sleep-promoting and used at night, minimizing functional conflict.

  • LL-37Complementary

    No documented conflict

    Both support angiogenesis, tissue repair, and anti-inflammatory signaling, though Semax is oriented toward neuroprotection via BDNF/NGF-TrkB pathways and LL-37 toward peripheral wound healing via VEGF/EGFR. Overlap is modest and context-dependent rather than a targeted combination.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms support the three claimed shared dimensions: (1) tissue_repair: LL-37 explicitly promotes angiogenesis, wound healing, and keratinocyte migration; Semax shows BDNF/NGF upregulation and neuroprotection, both tissue-repair mechanisms. (2) angiogenesis: LL-37 directly targets VEGF/VEGFA signaling and angiogenesis; Semax is tagged with angiogenesis in approved tags. (3) anti_inflammatory: LL-37 shows immunomodulation and NF-κB signaling; Semax shows anti-inflammatory/immune modulation and NF-κB modulation. The explanation accurately characterizes the relationship as complementary rather than synergistic—different tissue contexts (peripheral vs. neural) and different primary pathways (VEGF/EGFR vs. BDNF/TrkB) but overlapping functional outcomes. The modest, context-dependent overlap described is consistent with the mechanisms provided.

    Shares tissue repair · angiogenesis · anti inflammatory

  • Alpha-MSHStack with caution

    Worth caution

    Semax is an ACTH(4-10) analog that is reported to act as an antagonist or partial agonist at melanocortin receptors. Because alpha-MSH is a full melanocortin agonist, Semax could partially oppose alpha-MSH's melanocortin-driven effects (pigmentation, appetite, central signaling) even though both share broad anti-inflammatory/NF-κB activity — worth understanding if you expect additive melanocortin action.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    The mechanisms clearly establish both shared dimensions (anti_inflammatory and NF_kB_modulation are explicitly listed in approved tags for both peptides) and justify the caution relationship. Alpha-MSH is described as a full melanocortin agonist across MC1R, MC3R, MC4R, MC5R with NF-κB suppression effects. Semax is explicitly described as a proposed antagonist/partial agonist at melanocortin receptors and also shows NF-κB modulation. The explanation correctly identifies that despite sharing anti-inflammatory pathways, Semax's antagonistic/partial agonist activity at melanocortin receptors could oppose alpha-MSH's full agonist effects on melanocortin-dependent outcomes (pigmentation, appetite, central signaling). This represents a genuine mechanistic conflict at the receptor level that warrants caution when combining them, even though both modulate NF-κB and inflammation through potentially different pathways.

    Shares anti inflammatory · NF kB modulation

  • CerebrolysinComplementary

    May be complementary

    Both upregulate BDNF and act via TrkB, reduce neuroinflammation, and modulate dopaminergic tone, but Semax (an ACTH fragment) adds enkephalinase inhibition and its own neurotrophin induction. Different upstream triggers converging on the same neuroprotective/nootropic output make them a plausible complementary nootropic pair. Human combination data are lacking.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    The mechanism descriptions clearly establish all four claimed shared dimensions: (1) BDNF_signaling—both explicitly upregulate BDNF and target TrkB receptor; (2) dopaminergic_system—Cerebrolysin lists kinase inhibition affecting dopaminergic system and dopaminergic_system tag; Semax lists dopaminergic modulation and dopaminergic_system tag; (3) anti_inflammatory—both reduce neuroinflammation (Cerebrolysin via microglia modulation and TNF-α downregulation; Semax via immune modulation and NF-κB modulation); (4) neurogenesis—both have neurogenesis tags and mechanisms supporting it. The explanation correctly identifies convergence on neuroprotective/nootropic outcomes via different upstream mechanisms (Cerebrolysin via TrkA/TrkB/GFRα1 and multiple kinase pathways; Semax via μ-opioid receptor, melanocortin receptors, and enkephalinase inhibition). The claim that Semax adds enkephalinase inhibition (distinct from Cerebrolysin's endorphinergic effects via peptide fragments) is supported by the mechanisms. The 'complementary' relationship type is justified by the shared dimensions combined with mechanistically distinct upstream triggers converging on similar outputs, which is the hallmark of complementarity.

    Shares dopaminergic system · anti inflammatory · neurogenesis · BDNF signaling

  • NoopeptComplementary

    May be complementary

    Both are cognitive-enhancing peptides that raise BDNF/NGF and act through the TrkB neurotrophin pathway, but by different upstream routes — Noopept via its cycloprolylglycine metabolite modulating AMPA/TrkB, and Semax via ACTH-fragment neurotrophin signaling. They converge on the same goals (memory, attention, neuroprotection, anxiolysis) and are commonly used together in nootropic practice, making the pairing potentially additive rather than redundant.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    The mechanism descriptions clearly establish both shared dimensions: (1) anti_inflammatory — both peptides have documented anti-inflammatory effects (Noopept: 'Antioxidant and anti-inflammatory action'; Semax: 'Anti-inflammatory / immune modulation'); (2) BDNF_signaling — both explicitly target BDNF/NGF neurotrophin pathways via TrkB receptor activation (Noopept: 'BDNF / NGF neurotrophin signaling' and 'TrkB receptor (neuroprotection via activation)'; Semax: 'BDNF/NGF-TrkB neurotrophin signaling' and 'TrkB receptor'). The explanation correctly identifies convergent endpoints (memory, attention, neuroprotection, anxiolysis) achieved through distinct upstream mechanisms (Noopept via AMPA/cycloprolylglycine; Semax via ACTH-fragment/enkephalinase inhibition), which justifies the 'complementary' relationship type as additive rather than redundant. The mechanisms support this characterization.

    Shares anti inflammatory · BDNF signaling

  • DavunetideComplementary

    No documented conflict

    Both are short neuroactive peptides aimed at cognitive protection through non-overlapping mechanisms: davunetide stabilizes microtubules and lowers tau phosphorylation, whereas semax drives BDNF/NGF-TrkB neurotrophin signaling. Together they address structural stability and growth-factor support.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms explicitly include anti-inflammatory activity as documented effects. Davunetide shows anti-inflammatory activity through microtubule stabilization and tau regulation pathways. Semax shows anti-inflammatory/immune modulation effects through BDNF/NGF-TrkB signaling, NF-kB modulation, and interferon pathway modulation. The proposed relationship correctly identifies that both peptides achieve anti-inflammatory effects through distinct, non-overlapping mechanisms (microtubule-tau pathway vs. neurotrophin-immune signaling), making them complementary in this shared dimension. The explanation accurately reflects the mechanistic basis for complementarity.

    Shares anti inflammatory

  • CortexinComplementary

    May be complementary

    Cortexin supports neuronal survival through anti-excitotoxic, anti-apoptotic and neurotrophic actions, while Semax (an ACTH fragment) drives BDNF/NGF-TrkB signaling and cognitive enhancement by a distinct mechanism. Both converge on neuroprotection, neurogenesis and improved memory/attention, so they can complement each other rather than overlap.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly establish the four claimed shared dimensions: (1) dopaminergic_system—Cortexin explicitly modulates dopaminergic balance; Semax explicitly modulates serotonergic and dopaminergic systems; (2) anti_inflammatory—both mechanisms list anti-inflammatory effects as primary; (3) neurogenesis—both approved tags include neurogenesis, supported by Cortexin's neurotrophic support and Semax's BDNF/NGF upregulation; (4) BDNF_signaling—Cortexin engages BDNF-like/NGF-like neurotrophic signaling; Semax explicitly targets BDNF/NGF-TrkB signaling. The explanation correctly identifies that they achieve neuroprotection and cognitive enhancement through distinct mechanisms (Cortexin via glutamatergic/GABAergic/caspase modulation; Semax via TrkB/CREB/enkephalinase pathways), making them complementary rather than redundant. The mechanisms support convergence on shared functional outcomes without direct target overlap.

    Shares dopaminergic system · anti inflammatory · neurogenesis · BDNF signaling

  • P21Same downstream effect

    May be complementary

    P21 raises BDNF that then activates TrkB; Semax also upregulates BDNF/NGF and signals through TrkB and CREB. Both end up driving the same BDNF/TrkB neurotrophic and neurogenic output through different starting points, so they are potentially additive for memory and neuroprotection rather than redundant. Monitor for over-stimulation, since both also touch CREB and plasticity pathways.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly converge on BDNF/TrkB signaling and neurogenesis. P21 upregulates BDNF expression which activates TrkB, and Semax directly upregulates BDNF/NGF and signals through TrkB. Both activate CREB and drive neurogenesis through overlapping downstream pathways (PI3K/Akt and BDNF/TrkB for P21; BDNF/NGF-TrkB and CREB for Semax). The proposed relationship accurately identifies that despite different mechanisms of action (P21 as CNTF mimetic, Semax as ACTH-derived peptide), they converge on the same neurogenic and BDNF-signaling outputs, making them potentially additive rather than redundant. The shared dimensions of neurogenesis and BDNF_signaling are explicitly supported by both mechanisms.

    Shares neurogenesis · BDNF signaling

  • KlothoComplementary

    No documented conflict

    Both act as neuroprotective, anti-inflammatory agents in the brain through different routes — Semax drives BDNF/NGF-TrkB neurotrophic signaling and downregulates inflammatory mediators, while Klotho modulates NMDA GluN2B synaptic signaling and suppresses NF-κB/oxidative stress. Their cognitive-protective effects are additive from separate mechanisms.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly support the proposed complementary relationship with the shared dimensions of anti_inflammatory and NF_kB_modulation. Klotho's mechanism explicitly lists NF-κB signaling modulation and anti-inflammatory activity through multiple pathways (NLRP3 inflammasome, Nrf2, FoxO). Semax's mechanism explicitly lists NF_kB_modulation and anti_inflammatory/immune modulation effects. The explanation accurately describes their distinct mechanistic routes: Semax operates through BDNF/TrkB neurotrophin signaling and inflammatory mediator downregulation, while Klotho operates through NMDA receptor modulation and NF-κB/oxidative stress suppression. Both mechanisms confirm neuroprotective and anti-inflammatory effects via different pathways, making them genuinely complementary rather than redundant. The claim of additive cognitive-protective effects is supported by Klotho's cognitive/synaptic enhancement and Semax's nootropic effects operating through distinct mechanisms.

    Shares anti inflammatory · NF kB modulation

  • PinealonComplementary

    No documented conflict

    Both support neuroprotection and neurogenesis but by completely different mechanisms — Semax via BDNF/TrkB neurotrophin signaling and Pinealon via proposed direct gene/DNA regulation and antioxidant enzyme upregulation. Different upstream targets converging on neuronal survival make this a plausibly complementary neuroprotective pairing.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms explicitly support neurogenesis and neuroprotection through distinct pathways: Semax via BDNF/NGF-TrkB neurotrophin signaling and CREB activation; Pinealon via MAPK/ERK modulation, antioxidant enzyme expression (SOD2, GPX1), and caspase-3/p53 apoptotic pathway inhibition. The proposed relationship correctly identifies that they converge on neuronal survival and neurogenesis through different upstream mechanisms (growth factor signaling vs. gene regulation/antioxidant defense), which is the definition of complementarity. The shared dimension of neurogenesis is explicitly tagged for both peptides, and the explanation accurately reflects the mechanistic divergence described in both mechanism profiles.

    Shares neurogenesis

Safety and side effects

Safety and Tolerability

Preclinical studies describe a broad therapeutic window and low toxicity, with minimal adverse effects and generally good tolerability reported in Russian clinical settings.

Reported potential adverse effects

  • Mild nasal irritation (with intranasal use)
  • Headaches
  • Restlessness
  • Slight anticoagulant effects

Cautions

  • Caution is advised in severe psychiatric disorders, particularly bipolar disorder.
  • Not recommended in pregnancy or breastfeeding due to limited safety data.
  • Semax is not reported to cause traditional stimulant-like tolerance, though receptor-sensitivity adjustments may occur with prolonged continuous use; breaks are suggested to allow neurotrophin receptor systems to normalize.

Key uncertainties

There is little human evidence on side effects, no systematic adverse-event reporting by Western standards, unknown drug interactions, and no long-term safety data. Because Semax is not FDA-regulated, products from non-regulated sources carry potential contamination and quality-control risks. Semax is not FDA-approved in the United States.

Reconstitution and handling

Preparation and Administration

No dose has been established for this compound. No regulatory label exists for it, so the figures below are what sources report — not guidance.

Semax has good water solubility and is usually administered intranasally, typically formulated as a 0.1% or 1% aqueous solution. It demonstrates CNS penetration via the olfactory/intranasal route with high intranasal bioavailability; intranasal Tmax is ~5-15 minutes.

Dosing Ranges Reported in Sources

These figures are reported from the literature and vendor/expert-opinion sources and are not dosing advice.

Acute ischemic stroke (Russian clinical literature):

  • ~12 mg/day intranasal for moderate severity; ~18 mg/day for severe stroke, for 5-10 days.
  • One randomized trial of 100 patients used 12 mg/day intranasal for 5 days.
  • A 110-patient study used 6000 µg/day intranasally in two 10-day courses separated by a 20-day interval.

Cognitive enhancement (clinical/Russian literature):

  • Intranasal 0.015-0.050 mg/kg; clinical studies used 250-1000 µg/kg.

Non-clinical / anecdotal ranges:

  • Intranasal: 200-2,000 µg daily; nasal spray starting ~300 µg, maintenance 300-1,000 µg, up to 3,000 µg in some cases.
  • Subcutaneous: starting 100-200 µg daily, maintenance 200-500 µg, up to 1,000 µg; other sources cite 0.3-0.8 mg subcutaneously.

Cycling and Duration

Treatment courses are typically 10-14 days (or 10-30 days in Russian protocols), repeatable after rest periods. Injectable cognitive-enhancement cycles are described as 4-8 (up to 12) weeks with 2-4 week breaks between cycles. Breaks are recommended to allow neurotrophin receptor systems to normalize.

Pharmacokinetic Notes

Semax is metabolized by peptidase activity and eliminated by renal excretion. Plasma clearance is rapid (reported as minutes to ~1-2 hours depending on source), but functional effects persist much longer — roughly 12-24 hours after intranasal dosing — likely reflecting downstream neurotrophin effects (BDNF peaking ~8 hours, elevated 24 hours or more) and possibly stable active metabolites.

Sources

Ordered by evidence quality — the strongest first.

  1. PRIME PubMed | [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)](opens in a new tab)
    Tier 1Web · unboundmedicine.com
  2. Functional Connectomic Approach to Studying Selank and Semax Effects.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2020
  3. Meta-analysis: Semax effectiveness in the acute period of stroke - Shmonin - Bulletin of Rehabilitation Medicine(opens in a new tab)
    Tier 1Web · journals.eco-vector.com · 2018
  4. [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. - Abstract - Europe PMC(opens in a new tab)
    Tier 1Web · europepmc.org · 2018
  5. Semax and N Acetyl Semax-Amide: discovery, actions, safety, animal data, and development(opens in a new tab)
    Tier 2Web · hvm.bioflux.com.ro
  6. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis(opens in a new tab)
    Tier 2Web · pmc.ncbi.nlm.nih.gov
  7. The Potential of the Peptide Drug Semax and Its Derivative for ...(opens in a new tab)
    Tier 2Web · pmc.ncbi.nlm.nih.gov
  8. Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2025
  9. Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2025
  10. ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  11. 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.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  12. Brain Protein Expression Profile Confirms the Protective Effect of the ACTHPGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2021
  13. Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2021
  14. Novel Insights into the Protective Properties of ACTHPGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2020
  15. Semax, an analog of ACTH, regulates expression of immune response genes during ischemic brain injury in rats.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2017
  16. Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  17. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2006
  18. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2005
  19. N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1991
  20. Semax — Cognitive Vitality For Researchers(opens in a new tab)
    Tier 3Web · alzdiscovery.org
  21. Semax Cycle Length: How Long Can You Safely Run It?(opens in a new tab)
    Tier 3Web · redfoxpeptides.is
  22. Semax Peptide | Focus & Brain Support(opens in a new tab)
    Tier 3Web · paragonsportsmedicine.com
  23. Semax: The Ultimate Guide to Cognitive Enhancement and Neuroprotection(opens in a new tab)
    Tier 3Web · youtube.com
  24. Superpower(opens in a new tab)
    Tier 3Web · superpower.com
  25. What is the appropriate dosing, safety, and efficacy of the synthetic peptide Semax for neurological conditions?(opens in a new tab)
    Tier 3Web · droracle.ai
  26. Semax Half-Life: Minutes Intranasal (estimated) — Pharmacokinetics & Evidence Review | Halflife Labs(opens in a new tab)
    Tier 3Web · halflife-labs.com · 2026
  27. Semax: Research Evidence & Safety Profile | PeptideInsight(opens in a new tab)
    Tier 3Web · peptideinsight.com · 2026
  28. Semax — Molecular Specifications & Research Monograph | Peptide Biologix(opens in a new tab)
    Tier 4Web · peptidebiologix.com
  29. Total Synthesis of Alloviroidin.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2019
  30. Antibiotic glycosyltransferases.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2003