Section 01
What it's used for
Approved for Stroke Recovery
A 1% solution is approved in Russia for acute ischemic stroke. Human studies show faster recovery and better motor function when given early, based on clinical exams, not brain scans. It may work by raising BDNF, a nerve-survival protein.
▸Clinical wording
Semax (1% solution) is approved in Russia for treatment of acute ischemic stroke. Clinical studies demonstrate accelerated regression of neurological deficits and improved motor performance when administered during the acute period, based on clinical and electrophysiological endpoints rather than imaging measures of infarct volume. The proposed neuroprotective mechanism involves BDNF-mediated neuronal survival.
Used as a Nootropic
Its best-known use is as a nootropic (cognition booster). A research review describes it as boosting working memory and attention in people, but no controlled trial measuring memory, learning speed, or processing performance was found.
▸Clinical wording
Semax's most established use is as a nootropic. A review of semax research describes it as stimulating operative (working) memory and attention in humans, but no specific controlled clinical trial quantifying working memory, learning speed, or information-processing performance was located. Proposed mechanisms include BDNF-mediated synaptic plasticity and enhanced monoaminergic neurotransmission.
Approved for Optic Nerve Damage
Approved in Russia for optic nerve atrophy (nerve damage that impairs vision). Human trials show better visual sharpness, wider field of vision, and improved retinal nerve cell survival, thought to work via BDNF protecting the optic nerve.
▸Clinical wording
Semax is approved for treatment of optic nerve atrophy in Russia. Clinical trials demonstrate improved visual acuity, expanded visual fields, and enhanced retinal ganglion cell survival through BDNF-mediated neuroprotection of optic nerve fibers.
Unproven for ADHD
Vendor and community sources sometimes suggest this peptide for ADHD, but no clinical trial in ADHD patients was found. The only related paper, from 2007, is a theoretical proposal, not a study, with no attention-test performance data.
▸Clinical wording
Semax is sometimes discussed in vendor and community material as a potential option for ADHD and attention deficits, but no published clinical trial of semax in ADHD patients was found. The only related publication is a 2007 hypothesis paper proposing semax as a candidate ADHD treatment; it is a theoretical discussion, not a clinical study, and reports no attention-task performance data.
Early Lab Findings Only
In lab-dish studies, it affected copper-triggered amyloid-beta clumping on artificial membranes and boosted survival of rat brain neurons roughly 1.5 to 1.7 times — early cell-level findings, not results from an Alzheimer's disease model.
▸Clinical wording
In vitro studies show semax affects copper-induced amyloid-beta aggregation in artificial membrane models and increases survival of rat basal forebrain cholinergic neurons roughly 1.5- to 1.7-fold; these are preliminary cell-level and in vitro findings, not results from an Alzheimer's disease model. A study of semax in a 6-OHDA rat model of Parkinson's disease found no significant effect on motor behavior, and no GDNF upregulation by semax has been reported.
Approved for Stomach Ulcers
Approved in Russia for peptic ulcers. It is thought to protect the stomach lining and speed ulcer healing by improving blood flow and cell protection in the stomach, through melanocortin (hormone-related) pathways.
▸Clinical wording
Approved in Russia for this indication, semax enhances gastric mucosal protection and accelerates ulcer healing through melanocortin-mediated effects on gastric microcirculation and cytoprotection.
Section 02
Mechanism of Action
The strongest driver of a growth protein
- Semax is described as one of the most potent known inducers of a nerve growth protein (BDNF).
- It raises that protein's gene activity two- to fivefold in the memory hub and cortex.
- The protein drives branching of neurons, stronger synapses, neuron survival and new neuron growth.
- Those processes are the biological basis of learning, memory and cognitive resilience.
▸Clinical wording
BDNF Upregulation (Primary Mechanism)
Semax is one of the most potent pharmacological inducers of brain-derived neurotrophic factor. It increases BDNF mRNA expression in hippocampus and cortex by 2-5 fold through activation of the BDNF gene promoter (exon IV). BDNF drives dendritic branching, synaptic plasticity (LTP), neuronal survival, and neurogenesis — the biological substrates of learning, memory, and cognitive resilience.
Acting on a stress-hormone receptor family
- Semax works through melanocortin receptors in the brain, which raise an internal messenger (cAMP).
- In the memory hub this signalling is described as strengthening the fixing of memories.
- In the cortex the same receptors are linked to attention and executive function.
- Unlike the hormone ACTH it lacks adrenal receptor activity, so it drives no steroid production.
▸Clinical wording
Melanocortin System Activation
Semax acts through melanocortin receptors (MC3R and MC4R) in the brain, which are Gs-coupled GPCRs that increase cAMP signaling. Melanocortin activation in hippocampus enhances memory consolidation, while cortical MC4R signaling improves attention and executive function. Importantly, semax lacks the MC2R (adrenal) activity of ACTH, explaining its absence of steroidogenic effects.
Turning over mood and motivation chemicals
- Semax increases the turnover of serotonin and dopamine in key brain regions.
- It boosts the enzymes that build both chemicals and the transporter that packages them.
- It also modulates the enzyme that breaks them down, which is tied to mood and attention.
▸Clinical wording
Serotonin and Dopamine Modulation
Semax increases serotonin and dopamine turnover in key brain regions. It enhances tryptophan hydroxylase and tyrosine hydroxylase activity, increases vesicular monoamine transporter expression, and modulates monoamine oxidase activity. This combined monoaminergic enhancement contributes to mood improvement, motivation, and sustained attention.
Several ways of shielding neurons
- Semax limits damage from excess glutamate and from calcium overload inside neurons.
- It raises two antioxidant enzymes, reducing oxidative stress in brain tissue.
- It also dampens the internal cascade that pushes cells into programmed death.
- The source frames these mechanisms as most relevant to ischaemic stroke and neurodegenerative conditions.
▸Clinical wording
Neuroprotective Mechanisms
Semax protects neurons through multiple pathways: inhibition of glutamate excitotoxicity, reduction of intracellular calcium overload, suppression of oxidative stress (via SOD and catalase upregulation), and inhibition of apoptotic cascades (reduced caspase-3 activation, increased Bcl-2/Bax ratio). These neuroprotective mechanisms are particularly relevant in ischemic stroke and neurodegenerative conditions.
Quieting inflammation in brain tissue
- Semax reduces activation of the brain's resident immune cells and lowers inflammation there.
- It turns down inflammatory messengers such as tumour necrosis factor alpha and interleukin-1 beta.
- This is described as running through one melanocortin receptor and adding to neuroprotection.
▸Clinical wording
Anti-Inflammatory Neuroimmunomodulation
Semax reduces microglial activation and brain inflammation through downregulation of pro-inflammatory cytokines (TNF-α, IL-1β) and chemokines. This anti-neuroinflammatory effect is mediated through MC4R signaling and contributes to neuroprotection in inflammatory brain conditions.
Section 03
Biological Pathways
- BDNF/TrkB/CREB PathwaySemax-induced BDNF binds TrkB, activating PLCγ, PI3K/Akt, and MAPK/ERK cascades; ERK phosphorylates CREB, driving transcription of plasticity and memory genes (Arc, Fos, Zif268).
- cAMP/PKA/CREB via Melanocortin ReceptorsMC3R/MC4R activation generates cAMP via Gαs-adenylyl cyclase coupling; PKA phosphorylates CREB, converging with BDNF/TrkB signaling to enhance plasticity gene transcription.
- Nrf2/HO-1 NeuroprotectionSemax activates the Nrf2 pathway, inducing heme oxygenase-1 (HO-1) and other cytoprotective enzymes; carbon monoxide and biliverdin produced by HO-1 add anti-inflammatory and antioxidant neuroprotection.
- NGF/GDNF Neurotrophic CascadeBeyond BDNF, semax upregulates NGF and GDNF, supporting survival of cholinergic and dopaminergic neurons respectively, giving broader neurotrophic support than single-target cognitive enhancers.
Section 04
Dosage Information
Met-Glu-His-Phe-Pro-Gly-Pro| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Intranasal — 0.1% drops | Russian label, brain-vessel and cognitive disorders | One drop is 0.05 mL and 50 µg; 2–3 per nostril. Single 200–2,000 µg (3–30 µg/kg), daily 500–5,000 µg (7–70 µg/kg), 3–5 days, up to 14 | A 25-fold range, written for stroke aftermath, brain damage and optic-nerve disease. No trial has dosed a healthy adult for the cognitive effect. |
| Intranasal — 1% drops | Russian label, acute stroke, adults only | The same drop, 500 µg. Moderate 2,000–3,000 µg 3–4×/day (6,000–12,000 daily); severe 3,000–4,000 µg 4–5×/day (12,000–20,000). 10 days | Hospital dosing for the first days after a stroke — up to forty times the 0.1% daily amount, from an identical bottle. Mixing the two is a tenfold error. |
| Intranasal — stroke trials | Meta-analysis of Russian trials, acute stroke | 1% solution, 12–18 mg a day for 10–14 days. Of eight trials and 654 patients, only three trials and 181 patients could be pooled | Benefit appeared only in moderate and severe strokes, not mild ones. The pooled trials are mixed and all Russian; their authors ask for a blinded study. |
| Intranasal — self-administration | Sprays sold as a research chemical outside Russia | Sprays are labelled 200 µg per spray; the circulating 400–8,000 µg a day in 2–4 doses is the Russian 0.1% label copied across | Not a finding but the label restated, and the pump's puff is not the 0.05 mL drop it counts in. Most are N-Acetyl Semax Amidate, with no dosing data in people. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
- Protocol 01
Semax + Selank Cognitive Stack
Nootropic peptide stack for focus, memory, anxiety reduction, and neuroprotection.
- Focus
- Cognitive
- Level
- Beginner
- Duration
- 4–8 weeks
Section 06
Stability & Storage
Lyophilised powder
Semax ships as lyophilised powder, kept at −20°C for long-term stability (18-24 months) or at 2-8°C for 6 months, protected from light because the methionine residue is prone to photooxidation. Commercial 0.1% and 1% nasal spray solutions (sold in Russia) have a 2-year shelf life at 2-8°C. As with selank, the Pro-Gly-Pro C-terminal extension shields the peptide from carboxypeptidase breakdown.
After reconstitution
In solution, the N-terminal methionine remains prone to oxidation; research formulations sometimes add antioxidants such as ascorbic acid or extra methionine to extend stability. Intranasal delivery reaches the CNS directly through the olfactory epithelium, while subcutaneous injection is used as an alternative research route.
Section 07
Side Effects & Precautions
Semax has a safety profile documented across decades of clinical use in Russia, with no serious adverse effects reported at approved dosing regimens.
Nasal Irritation
Mild burning or tingling in the nasal passages can occur immediately after administration, typically lasting less than 1 minute. It is most common with the 1% (high-concentration) formulation.
No Cortisol or Adrenal Stimulation
Despite its ACTH-derived structure, semax does not activate MC2R (adrenal) receptors and produces no measurable increase in cortisol or adrenal steroids — a safety finding validated in multiple studies.
No Dependence or Withdrawal
There is no evidence of tolerance, dependence, or a withdrawal syndrome with chronic semax use. It can be discontinued abruptly without adverse effects.
Mild Effects On Mood And Head
- Occasional mild headache during initial use has been reported, typically self-limiting.
- Some users report mild restlessness or irritability, possibly tied to higher dopaminergic and noradrenergic tone; it is dose-dependent and eases with adjustment.
Section 08
Regulatory Status
It is an approved prescription medicine in Russia, an unapproved research compound everywhere else, and it is one of six peptides a U.S. FDA advisory committee recently recommended for the compounding pathway.
Russia
Approved, prescription-only in both strengths
The Ministry of Health registers the two concentrations separately: 0.1% nasal drops under ЛП-№(009449)-(РГ-RU) since 26 March 2025, and 1% drops under ЛП-№(010596)-(РГ-RU) since 18 June 2025, both held by AO «INPC Peptogen».
Ukraine and Belarus
Registrations expired and were not renewed
The Ukrainian authorisations UA/1565/01/01 and UA/1565/01/02 ran from 28 July 2009 to 28 July 2014; the Belarusian authorisation 4892/01, covering the 0.1% solution, ran from 31 January 2001 to 31 January 2006. Neither register lists Semax today.
FDA review
Not approved; a panel recommends compounding
On 24 July 2026 the Pharmacy Compounding Advisory Committee voted 8 to 5 to add Semax to the 503A Bulks List, alongside BPC-157, KPV, TB-500, MOTS-C and Epitalon. The vote does not bind the FDA: the list changes only through formal rulemaking, and none of the six had been added as of this check.
US, EU, UK and Australia
Not approved; sold as a research chemical
Outside Russia no medicines regulator has cleared Semax for any indication; it is marketed by research-chemical suppliers labelled "not for human consumption," without the quality or dosing oversight an approved drug carries.
WADA
No explicit listing found
Semax does not appear by name on WADA's Prohibited List. It shares its origin with ACTH(4-10), and ACTH itself is banned under category S2 (peptide hormones), but no ruling establishes Semax's own anti-doping status — treat it as unresolved, not cleared.
Approval in Russia does not extend to any other jurisdiction, and a compounding-committee recommendation is not itself an FDA approval. Regulatory status changes over time — verify the current position of your own regulator before relying on any of this.
We cover the 23–24 July 2026 vote of the FDA's Pharmacy Compounding Advisory Committee (PCAC) separately, in «The 2026 PCAC Peptide Vote» (/en/articles/fda-pcac-2026-peptides). In short: on 24 July the committee recommended adding Semax to the 503A Bulks List — 8 votes to 5, against the written position of the FDA's own reviewers. The recommendation binds no one: the list changes only through formal rulemaking, which usually takes 8–12 months, and even a place on it would not make Semax an approved medicine.
Section 09
Research Studies
- [1]Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampusDolotov OV, Karpenko EA, Inozemtseva LS, et al. · Brain Research · 2006
- [2]Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrainDolotov OV, Karpenko EA, Seredenina TS, et al. · Journal of Neurochemistry · 2006
- [3]Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10Agapova TY, Agniullin YV, Shadrina MI, et al. · Neuroscience Letters · 2007
- [4]Semax, An ACTH(4-10) Analogue with Nootropic Properties, Activates Dopaminergic and Serotoninergic Brain Systems in RodentsEremin KO, Kudrin VS, Saransaari P, et al. · Neurochemical Research · 2005
- [5]Synacton and individual activity of synthetic and natural corticotropinsVyunova TV, Andreeva LA, Shevchenko KV, Myasoedov NF. · Journal of Molecular Recognition · 2017
- [6]Novel synthetic analogue of ACTH 4-10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemiaBashkatova VG, Koshelev VB, Fadyukova OE, et al. · Brain Research · 2001
- [7]Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortexRomanova GA, Silachev DN, Shakova FM, et al. · Bulletin of Experimental Biology and Medicine · 2006
- [8]The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysisMedvedeva EV, Dmitrieva VG, Povarova OV, et al. · BMC Genomics · 2014
- [9]Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in ratsMedvedeva EV, Dmitrieva VG, Limborska SA, Myasoedov NF. · Molecular Genetics and Genomics · 2017
- [10]The efficacy of semax in the treatment of patients at different stages of ischemic strokeGusev EI, Martynov MY, Kostenko EV, et al. · Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova · 2018
Section 10
Frequently Asked Questions
In Russia semax is approved for stroke recovery, optic nerve atrophy and peptic ulcer disease, based on trials measuring those specific endpoints. For its most searched-for use — cognition in healthy people — a review describes it as stimulating working memory and attention, but no specific controlled trial quantifying memory, learning speed or information processing was located; for ADHD, the only related publication is a 2007 theoretical paper, not a clinical trial.
Semax is approved only in Russia, under two separate authorisations — ЛП-№(009449)-(РГ-RU) for the 0.1% nootropic drops and ЛП-№(010596)-(РГ-RU) for the 1% drops used in stroke care — and BOTH strengths are prescription-only. Its Ukrainian and Belarusian registrations expired in 2014 and 2006 and were never renewed. It has never been reviewed by the FDA or EMA and is treated as a research peptide in Western countries. It is not itself on the WADA prohibited list, though its ACTH-derived structure invites caution since ACTH itself is banned under WADA's S2 category — semax lacks ACTH's steroidogenic activity, which is the pharmacological basis for treating it differently.
The 0.1% label for cognitive and vascular disorders runs 500–5,000 µg a day; the 1% label, used only in hospitals for acute stroke, runs up to 20,000 µg a day — a roughly forty-fold difference from an otherwise identical-looking bottle. Confusing the two concentrations is effectively a tenfold dosing error, and no trial has separately dosed a healthy adult for a purely cognitive effect.
No published data address combining semax with SSRIs, Wellbutrin or stimulant ADHD medications. The documented side-effect profile — nasal irritation, headache, occasional irritability — comes from decades of use in Russia at labelled doses alone, not from any interaction study.
In the pooled stroke trials, semax was given for 10–14 days and benefit was assessed at the end of that course, appearing only in moderate and severe strokes rather than mild ones. No trial has measured how quickly a cognitive effect appears in a healthy adult, or how long it lasts after stopping.
Despite its ACTH-derived structure, semax does not activate adrenal (MC2R) receptors and produces no measurable rise in cortisol — a mechanism-based safety feature confirmed in multiple studies. Reported effects are mild: brief nasal burning with the higher-concentration 1% solution, occasional headache, and some reports of irritability linked to its dopaminergic and noradrenergic activity; no dependence or withdrawal has been documented.
The lyophilised powder is kept at −20°C for 18–24 months or 2–8°C for 6 months, protected from light because its methionine residue oxidises easily. The commercial nasal spray sold in Russia has a 2-year shelf life at 2–8°C; research formulations sometimes add antioxidants like ascorbic acid to slow the same oxidation once in solution.