Semax
A Russian nasal-drop drug with rat BDNF data and small human studies
Semax is a seven-amino-acid peptide built from a fragment of ACTH, the stress hormone, with a Pro-Gly-Pro tail. It is an approved medicine in Russia, given as nasal drops. In rats it raised BDNF in the hippocampus; in people the evidence is a set of small Russian studies in stroke and other conditions, few of them described as randomised.
What is it?
Semax is a heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro: the ACTH(4–7) fragment of adrenocorticotropic hormone joined to the tripeptide Pro-Gly-Pro. Papers describe it as an analogue of ACTH(4–10), a fragment long studied for effects on learning. It is an approved drug in Russia, given as nasal drops, and it came out of Russian research; most of the studies below were published there, several only in Russian with English abstracts.
The mechanistic case rests on rats. A single dose raised hippocampal BDNF protein 1.4-fold and exon III BDNF mRNA threefold, with more activation of its receptor, trkB, and treated rats did better on an avoidance-learning task. Semax binds specific sites in the basal forebrain, where intranasal doses raised BDNF within three hours. It also increased serotonin turnover in the striatum and, strikingly, amplified the dopamine release and hyperactivity caused by amphetamine.
The human evidence is broader than for most research peptides but thin in quality. Russian clinical reports describe faster recovery after ischaemic stroke, better visual function in optic nerve disease, faster healing of refractory ulcers (89.5% against 30.8% at day 14) and better quality of life, but not slower disease, in motor neuron disease. Group sizes are small or unreported, and the abstracts rarely describe randomisation or blinding. One placebo-controlled imaging study in 24 healthy volunteers found a change in brain network activity within minutes of a nasal dose.
In the US, FDA's own review for its July 2026 advisory meeting was unusually negative: of the seven peptides, semax was the only one where FDA said the evidence demonstrated a lack of effectiveness, and it flagged anticoagulant activity and amphetamine potentiation in animals. The committee voted to recommend it anyway, 8–5 with one abstention, on July 24, 2026. FDA has not acted, so US pharmacies cannot compound it (as of September 26, 2026).
Mechanism of Action
Semax was developed as a stabilised ACTH fragment, and the abstracts document four kinds of effect, almost all in rats and in laboratory systems. None of them has been tied to a clinical outcome in a controlled human trial, which is the gap FDA pointed to in 2026.
The binding and BDNF steps come from rats. In stroke patients, semax raised plasma BDNF; the recovery comparisons were with standard care, and the abstracts report no placebo.
Each step is tagged with where it was shown. A dashed red arrow marks a link the evidence does not establish.
The pathway in words
- Semax. A seven-amino-acid analogue of the ACTH(4-10) fragment, Met-Glu-His-Phe-Pro-Gly-Pro, given as nasal drops. Shown in: lab. Source: PubMed 16635254.
- A binding site in rat brain. Labelled semax bound rat basal forebrain membranes specifically and reversibly, with a dissociation constant of 2.4 nM. Shown in: animals. Source: PubMed 16635254.
- BDNF and its receptor. A single dose raised hippocampal BDNF up to 1.4-fold and activation of its receptor trkB 1.6-fold in rats, which learned avoidance better. Shown in: animals. Source: PubMed 16996037.
- BDNF in stroke patients. In 110 patients months after ischaemic stroke, semax raised plasma BDNF whether rehabilitation started early or late. Shown in: people. Source: PubMed 29798983.
- not shown against placebo. Better stroke recovery. The stroke studies here compared semax with standard care alone, one with 30 treated and 80 controls; the abstracts report no placebo. Shown in: people. Source: PubMed 11517472, 29798983.
BDNF and trkB
A single 50 µg/kg dose raised BDNF protein in the rat hippocampus 1.4-fold, phosphorylation of its receptor trkB 1.6-fold, and exon III BDNF and trkB mRNA threefold and twofold. Intranasal doses of 50 and 250 µg/kg raised BDNF in the basal forebrain within three hours but not in the cerebellum. BDNF supports synaptic plasticity, which is the basis of the nootropic claim.
Serotonin and dopamine
At 0.15 mg/kg, semax raised striatal 5-HIAA, a serotonin breakdown product, by 25% in tissue and up to 180% in extracellular fluid over one to four hours. It did not change dopamine on its own, but given 20 minutes before amphetamine it dramatically enhanced amphetamine's dopamine release and locomotor effects. That interaction is a safety signal as much as a mechanism.
Ischaemia and immunity
In rats with focal cerebral ischaemia, a genome-wide analysis found that the immune response was the process semax affected most: it enhanced antigen-presentation signalling and intensified ischaemia's effect on interferon signalling. The authors link these shifts to its protective effect in stroke models, and they tested its Pro-Gly-Pro tail separately.
Copper and oxidative stress
Semax binds copper(II) ions strongly. In laboratory experiments it pulled copper out of copper–amyloid-beta complexes, reduced the reactive oxygen species those complexes generate, and protected SH-SY5Y neuron-like cells against the resulting oxidative stress. It is a test-tube result relevant to Alzheimer's research, with no clinical data behind it.
Published Research
About 44 papers in our evidence set match semax, most from Russian groups, and unlike most research peptides a good share are human studies. The eleven cards below were chosen because their abstracts say what was measured. Read the human cards for their design as much as their results: samples are small, and few describe randomisation or blinding.
Specific binding sites and BDNF in the rat forebrain
Radio-labelled semax bound rat basal forebrain membranes specifically and reversibly, needing calcium, with a dissociation constant of 2.4 nM, which points to a dedicated binding site. Given intranasally at 50 and 250 µg/kg, semax rapidly increased BDNF in the basal forebrain within three hours, but not in the cerebellum. The authors link its cognitive effects, at least in part, to that BDNF rise.
BDNF and trkB up in the hippocampus
A single application of 50 µg/kg raised hippocampal BDNF protein by up to 1.4 times and phosphorylation of its receptor trkB by 1.6 times, with threefold and twofold increases in exon III BDNF and trkB mRNA. Treated rats also made more conditioned avoidance responses, a learning measure. This study is the main basis for describing semax as a BDNF-raising nootropic.
Serotonin up, amphetamine amplified
Semax at 0.15 mg/kg raised striatal 5-HIAA, a serotonin metabolite, by 25% in tissue at two hours and up to 180% in extracellular fluid over one to four hours. On its own it did not change dopamine. Given 20 minutes before d-amphetamine, it dramatically increased amphetamine's effect on extracellular dopamine and on locomotion, an interaction worth knowing before combining it with stimulants.
Stroke model: immune genes shift
Genome-wide analysis of the cerebral cortex in rats with focal cerebral ischaemia found that semax affected the immune response more than any other process, enhancing antigen-presentation signalling and intensifying ischaemia's effect on interferon signalling. The authors also tested Pro-Gly-Pro, semax's C-terminal tail, to separate its contribution. It is a mechanism study for the stroke use, not an outcome trial.
Stroke rehabilitation: BDNF and Barthel scores
A total of 110 patients were studied about 3 or 7 months after ischaemic stroke, split into early and late rehabilitation groups, each with and without semax (two 10-day courses of 6,000 µg a day, 20 days apart). Semax raised plasma BDNF regardless of timing, and semax with high BDNF went with faster improvement and a better final Barthel index. The abstract does not say how patients were assigned.
Acute stroke: 30 treated, 80 controls
Thirty patients in the acute period of hemispheric ischaemic stroke received semax on top of intensive therapy, compared with 80 similar patients on conventional treatment. The authors report 'some influence' on the speed of neurological recovery, especially of motor deficits, with 12 mg a day in moderate strokes and 18 mg a day in severe ones, over 5 and 10 days. Nothing in the abstract suggests randomisation.
Optic nerve disease
Patients with vascular, toxic-allergic or inflammatory optic nerve disease and partial optic atrophy received semax as nasal drops or by endonasal electrophoresis alongside standard therapy, against a control group. The abstract reports better visual acuity, wider visual fields, improved electrical sensitivity and conductivity of the optic nerve, and better colour vision, but gives no patient numbers or effect sizes.
Brain imaging in healthy volunteers
Twenty-four healthy adults, average age 44, had resting-state fMRI before and 5 and 20 minutes after intranasal 1% semax (14 people) or placebo (10). The semax group showed a larger rostral, medial-frontal component of the default mode network, the brain network active at rest. It shows the drug alters brain activity quickly; it does not show better cognition.
Refractory peptic ulcers
Added to standard ulcer drugs, intranasal semax (1% solution, 2–4 drops three times a day for 10 days) was followed by ulcer healing by day 14 in 89.5% of patients with refractory peptic ulcers, against 30.8% of controls. The abstract gives no patient numbers and itself calls for further clinical studies, which is the right reading of a striking but unreplicated figure.
Motor neuron disease: mood, not disease course
In an open-label study, 27 patients with motor neuron disease took 12 mg of semax a day intranasally in two 10-day courses two weeks apart. It did not change the course of chronic denervation on EMG or clinical measures of functional decline. It did significantly improve total quality-of-life scores, through better emotional state and motivation, with the largest effect at day 10.
Copper and amyloid-beta in the test tube
Semax binds copper(II) with high affinity. In vitro it extracted copper from copper–amyloid-beta complexes, altered their redox cycling and lowered the reactive oxygen species they generate, and it protected SH-SY5Y cells against oxidative stress from copper-catalysed amyloid oxidation. The authors present it as a lead for Alzheimer's research; no animal or human testing is reported.
Pain sensitivity in rats and mice
Injected semax at 0.015-0.5 mg/kg reduced pain sensitivity in every rodent model tested, including hind-paw compression in rats and acetic-acid writhing in mice, while its parent fragment ACTH(4-10) worked only at 0.5 mg/kg.
What people say, and what was measured
Semax has a real clinical literature and almost all of it is Russian-language, published where the drug is registered and rarely replicated elsewhere. That is the honest frame for every claim below: not absent evidence, but evidence from one jurisdiction that the rest of the world has not reproduced.
It is proven in stroke recovery — it is a registered stroke drug in Russia.
Heard in: Zhurnal Nevrologii i Psikhiatrii, the Russian-language trial reports of semax in ischaemic stroke that the claim rests on (read October 1, 2026). Source
There are trials, and they are where the registration comes from: 110 patients followed for five months across early and late rehabilitation, dosed at 6,000 mcg a day in two ten-day courses, and an earlier acute-stroke study against 80 conventionally treated controls that settled on 12 mg daily for moderate and 18 mg for severe strokes. Both are Russian-language, neither has been replicated outside that system, and no regulator elsewhere has reviewed them. PMID: 29798983, 11517472
Tested in people; mixedIt is a nootropic that raises BDNF, so it improves cognition in healthy people.
Heard in: Grey Peptides listing review, October 1, 2026: listings sell it as a nootropic for focus and memory. Sellers are not named.
The BDNF part is measured, in rats: semax regulates BDNF and its receptor in the basal forebrain, and raises BDNF levels in cell work. The cognitive claim in healthy people has no trial here. A brain-imaging study in people looked at the default mode network, which is a measurement rather than a performance result. PMID: 16996037, 16635254, 30225715
Shown in animals or cells onlyIt works through the brain's own dopamine and serotonin systems, so it is safer than stimulants.
Heard in: Grey Peptides listing review, October 1, 2026: listings contrast it with stimulant nootropics. Sellers are not named.
Activation of dopaminergic and serotonergic systems was shown in rats, not people. Acting through endogenous systems is a mechanism, not a safety finding: no controlled safety study in healthy people appears in the sources on this entry. PMID: 16362768
Shown in animals or cells onlyIt helps the eyes, the gut and nerve damage too.
Heard in: Grey Peptides listing review, October 1, 2026: listings list optic nerve, ulcer and neuropathy uses. Sellers are not named.
Each of those has one small Russian-language report behind it: optic nerve disease, peptic ulcer, and chronic partial denervation. They are individual studies in one literature, not a demonstrated range of uses. PMID: 10741256, 12459874, 18379501
Tested in people; mixedEach claim is quoted from where it is said, never from a seller, and checked as of October 1, 2026 against the studies listed below.
Dosing Data
Semax is one of the few peptides in this encyclopedia with clinical dosing on record, because Russian studies used it as a drug. The regimens carded here are intranasal or unstated courses of 6–18 mg a day for 5 to 10 days, sometimes repeated, and a 1% solution for ulcers. The lower figure in our dataset, 250–600 µg two to three times a day as a 0.1% solution, is not one any study on this page tested.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Full Semax dosage guide — what the Russian clinical courses used, and how the smaller everyday doses in circulation compare
Side Effects & Contraindications
Reported Side Effects
The clinical abstracts on this page report outcomes, not adverse-event tables, so there is no systematic side-effect profile to quote. What the evidence does raise are two pharmacological signals from animals, plus the risks of unregulated supply.
Contraindications & Cautions
These cautions come from the pharmacology the studies describe and from FDA's July 2026 review, rather than from harm observed in trials.
Legal Status
Semax is an approved medicine in Russia and in none of the other jurisdictions below. In the US it went before FDA's advisory committee in July 2026, where FDA's own review was the most negative of the seven peptides considered. Status as of September 26, 2026.
Frequently Asked Questions
?Is semax an approved drug?
In Russia, yes: it is an approved medicine used as nasal drops. It is not approved by the FDA or in the EU, UK, Canada or Australia. Approval in one country does not mean the evidence would satisfy another regulator: FDA's 2026 review concluded that the evidence it examined demonstrated a lack of effectiveness.
?Does semax raise BDNF in humans?
In one stroke study, patients given semax had higher plasma BDNF throughout, and higher BDNF went with better recovery scores. The stronger evidence is from rats, where a single dose raised hippocampal BDNF protein 1.4-fold. Plasma BDNF in people is an indirect marker, not a measure of what happens in the brain.
?Is semax a proven nootropic?
No. The learning effects come from rats, and the only healthy-volunteer study on this page measured brain network activity on fMRI, not memory or attention. The Russian clinical studies target illness, such as stroke and eye disease, rather than cognitive enhancement in healthy people.
?Is semax safe?
The clinical abstracts here do not include adverse-event tables. Two signals from animals matter: it strongly amplified amphetamine's dopamine and locomotor effects in rats, and FDA's 2026 review flagged anticoagulant activity. Anyone taking stimulants or blood thinners has a specific reason for caution.
?Can a US pharmacy compound semax?
Not as of September 26, 2026. The Pharmacy Compounding Advisory Committee voted 8–5 on July 24, 2026 to recommend adding it to the 503A bulks list despite FDA's negative review. Only FDA can add it, through rulemaking, and it has not.
?What doses did the Russian studies use?
Courses of 6 to 18 mg a day for 5 to 10 days, sometimes repeated after a gap of two to three weeks, in stroke and motor neuron disease; the ulcer study used a 1% solution, two to four drops three times a day for 10 days. None of these is a US-approved regimen, and the studies behind them are small.
?Has semax been studied for trigeminal neuralgia?
Not in people. A PubMed search on October 6, 2026 for semax with trigeminal neuralgia, facial pain, neuralgia or neuropathic pain found no human study. Its pain research is in animals: in rats and mice, injected semax lowered pain sensitivity across several models (2007). That is not evidence it treats trigeminal neuralgia, which has approved treatments a neurologist can discuss.
References
- [pubmed] Dolotov OV, et al. "Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain." J Neurochem, 2006;97 Suppl 1:82-6. PMID: 16635254.
- [pubmed] Dolotov OV, et al. "Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus." Brain Res, 2006;1117(1):54-60. PMID: 16996037.
- [pubmed] Eremin KO, et al. "Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents." Neurochem Res, 2005;30(12):1493-500. PMID: 16362768.
- [pubmed] Medvedeva EV, et al. "Semax, an analog of ACTH((4-7)), regulates expression of immune response genes during ischemic brain injury in rats." Mol Genet Genomics, 2017;292(3):635-653. PMID: 28255762.
- [pubmed] Gusev EI, et al. "[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]." Zh Nevrol Psikhiatr Im S S Korsakova, 2018;118(3. Vyp. 2):61-68. PMID: 29798983.
- [pubmed] Gusev EI, et al. "[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]." Zh Nevrol Psikhiatr Im S S Korsakova, 1997;97(6):26-34. PMID: 11517472.
- [pubmed] Polunin GS, et al. "[Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease]." Vestn Oftalmol, 2000;116(1):15-8. PMID: 10741256.
- [pubmed] Lebedeva IS, et al. "Effects of Semax on the Default Mode Network of the Brain." Bull Exp Biol Med, 2018;165(5):653-656. PMID: 30225715.
- [pubmed] Ivanikov IO, et al. "Therapy of peptic ulcer with semax peptide." Bull Exp Biol Med, 2002;134(1):73-4. PMID: 12459874.
- [pubmed] Serdiuk AV, et al. "[The study of chronic partial denervation and quality of life in patients with motor neuron disease treated with semax]." Zh Nevrol Psikhiatr Im S S Korsakova, 2007;107(4):29-39. PMID: 18379501.
- [pubmed] Tomasello MF, et al. "Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing." Bioinorg Chem Appl, 2025;2025:4226220. PMID: 40496623.
- [pubmed] Myasoedov NF, et al. "Heptapeptide Semax and its neurotropic actions." Zh Vyssh Nerv Deiat Im I P Pavlova, 1999;49:646-652.
- [pubmed] Gusev EI, et al. "Neuroprotective effects of Semax in acute ischemic stroke." Zh Nevrol Psikhiatr Im S S Korsakova, 2005;105:41-46.
- [pubmed] Ivanova DM, et al. "Comparative study of analgesic potency of ACTH4-10 fragment and its analog semax." Bull Exp Biol Med, 2007;143(1):5-8. PMID: 18018999.
Sources & Citations
Every citation on this page is PubMed-indexed and has been checked against its record. Several Russian clinical studies are published only in Russian with English abstracts; the cards describe what those abstracts report and say when they leave out group sizes or controls. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.