Peptide guide
Semax: What It Is, Benefits, Side Effects and the Evidence
Semax is a synthetic peptide of seven amino acids, built from a fragment of the hormone ACTH but with no hormonal activity. It is used in Russia as a nasal solution for stroke recovery, optic nerve disease and cognitive problems. In animals it raises BDNF and acts on the serotonin and dopamine systems. The human studies are small and almost all Russian, and it is not approved in the US or EU.
Key takeaways
- A 7-amino-acid analogue of ACTH(4-10), given into the nose. It has no hormonal activity.
- Rats: specific binding sites in the brain and a rapid rise in BDNF within 3 hours of a nasal dose.
- Humans: Russian stroke studies report faster recovery; small studies in healthy volunteers show brain-network changes within minutes.
- No large independent trials, no long-term safety data, not approved by the FDA or EMA.
In this guide
What is Semax?
Semax is a heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. The first four amino acids come from adrenocorticotropic hormone (ACTH), positions 4 to 7, followed by a Pro-Gly-Pro tail. Unlike ACTH it is completely devoid of hormonal activity [1].
It was developed in Russia, where its creators describe it as one of the few regulatory peptides to go all the way from basic research to medical use [2]. It is given as a solution into the nose. That is what people mean by "Semax spray" or "Semax nasal spray": the published human studies used a 1% nasal solution [3].
How does Semax work?
- BDNF. In rats, Semax bound to specific sites in the basal forebrain, and a nasal dose of 50 or 250 micrograms per kg produced a rapid rise in brain-derived neurotrophic factor (BDNF) protein there after 3 hours [4]. In mice with poor exploratory learning, a course of Semax raised BDNF in the hippocampus and cortex [5].
- Serotonin and dopamine. In rodents it raised the serotonin metabolite 5-HIAA in the striatum to as much as 180% within 1 to 4 hours. On its own it did not change dopamine, but given before amphetamine it dramatically increased amphetamine's dopamine release [6].
- Enkephalins. In human serum it inhibited the enzymes that break down enkephalins, the body's own opioid peptides [7].
- Inflammation after stroke. In stroke patients it shifted the balance toward anti-inflammatory signals such as interleukin-10 [8].
Semax benefits: what the research shows
| Area | Model | Finding | Source |
|---|---|---|---|
| Acute ischemic stroke | Humans, 30 treated vs 80 controls | Faster recovery of neurological function, especially movement | [9] |
| Stroke rehabilitation | Humans, 110 patients | Higher plasma BDNF, faster functional recovery, better motor performance | [10] |
| Optic nerve disease | Humans | Better visual acuity, visual field and colour vision when added to standard therapy | [11] |
| Memory after oxygen deprivation | Humans, 73 patients | Effective in patients with memory disorders | [12] |
| Brain networks | Healthy volunteers, 24 people | Change in the default mode network 5 and 20 minutes after a nasal dose | [3] |
| Peptic ulcer | Humans | Added to standard drugs for stubborn ulcers: 89.5% healed by day 14 vs 30.8% in controls | [13] |
| BDNF | Rats, mice | Rapid rise in BDNF in the basal forebrain and hippocampus | [4] |
| Learning | Rats | Improved learning, more strongly by the nasal route than by injection | [14] |
The developers also report that it improves memory and attention in healthy men working under extreme conditions, with effects lasting 20 to 24 hours after a nasal dose [2].
How strong is the human evidence?
Weaker than the list above suggests. The clinical studies are small, most are in Russian, several had no placebo group, and many come from the groups that developed the drug. A Belgian drug-control laboratory that found Semax in seized products wrote that, to its knowledge, it has not completed any clinical trials [15]. That is the Western regulatory view.
For some popular uses there is no human trial at all:
- ADHD. The only paper is a hypothesis: because Semax raises BDNF and strengthens the effect of stimulants on dopamine in animals, the author proposed it could help [1]. It was never tested.
- Dementia and Alzheimer's. A lab study in artificial membranes found that Semax interfered with copper-driven clumping of amyloid-beta [16]. No patient study exists.
- Depression, autism, migraine, Parkinson's. Animal data or nothing.
Semax side effects
The developers' own review states that in no case did it produce negative side effects or complications [2]. That is a strong claim from an interested party, and it is not backed by a published safety trial with numbers.
The abstracts do contain two signals worth knowing:
- EEG changes. In patients with brain damage from oxygen deprivation, the EEG sometimes showed episodes of seizure-like (paroxysmal) activity after Semax, and the authors advised giving the first dose with EEG monitoring [12].
- It amplifies stimulants. In rodents it sharply increased amphetamine's effect on dopamine and movement [6]. Combining it with ADHD medication or other stimulants is untested in people.
Nasal irritation, headache and trouble sleeping are widely reported by users online. Those are anecdotes. I did not find them counted in any study.
Is Semax safe? Why is it not FDA approved?
- Approval: used as a medicine in Russia. Not approved by the FDA or the EMA. No company has run the large placebo-controlled trials those agencies require.
- Long-term use: no long-term safety data in PubMed.
- Product quality: outside Russia it is sold as a research chemical. Seized products containing Semax have been reported by a European control laboratory [15]. Nobody checks purity or dose for you.
- Who should be most careful: anyone with a seizure disorder, anyone on stimulants or antidepressants, and anyone pregnant or breastfeeding, for whom there is no data.
What dose was used in the studies?
These are the doses reported in the published abstracts. They describe research, they are not a recommendation.
- Acute stroke: 12 mg a day for moderate strokes and 18 mg a day for severe strokes, for 5 to 10 days [9].
- Stroke rehabilitation: 6,000 micrograms (6 mg) a day for 10 days, two courses with a 20-day gap [10].
- Peptic ulcer: 1% nasal solution, 2 to 4 drops three times a day for 10 days [13].
- Memory and attention in healthy people: 0.015 to 0.050 mg per kg into the nose, with effects described as lasting 20 to 24 hours [2].
All of these are nasal. I found no PubMed abstract with human pharmacokinetics, so I cannot give you a verified half-life. The "N-acetyl Semax amidate" versions sold online do not appear in the clinical studies above.
Semax vs Selank
They are sister peptides from the same Russian institutes, both with a Pro-Gly-Pro tail, but they are built from different parents and studied for different things. Semax comes from ACTH and is studied as a nootropic and neuroprotector. Selank comes from the immune peptide tuftsin and is studied for anxiety. The comparison is in Semax vs Selank, and the Selank evidence is in the Selank guide.
Frequently asked questions
What is Semax?
A synthetic seven-amino-acid peptide based on a fragment of ACTH, with no hormonal activity. It is used in Russia as a nasal solution for stroke recovery, optic nerve disease and cognitive problems.
What is Semax spray?
Semax given into the nose as a solution. The published human studies used a 1% nasal solution.
What are the benefits of Semax?
Russian clinical studies report faster recovery after ischemic stroke and better vision in optic nerve disease. In animals it raises BDNF and improves learning. Evidence in healthy people is limited to small studies.
What are the side effects of Semax?
No published trial counts them. The developers report none. One study in brain-injured patients saw seizure-like EEG activity after dosing, and in rodents Semax strongly amplified amphetamine. Online reports of nasal irritation and headache are anecdotal.
Is Semax safe?
Short courses appear to be tolerated in small Russian studies, but there is no long-term safety data and no large independent trial. It is not an approved drug in the US or EU.
Why is Semax not FDA approved?
No company has submitted the large placebo-controlled trials the FDA requires. Its clinical record consists of small Russian studies.
What dose of Semax was used in studies?
Stroke studies used 6 to 18 mg a day into the nose for 5 to 10 days. A review by its developers describes 0.015 to 0.050 mg per kg for memory and attention in healthy people.
Does Semax increase BDNF?
In rats, yes: a nasal dose raised BDNF protein in the basal forebrain within 3 hours. In stroke patients, Semax was associated with higher plasma BDNF.
Does Semax help ADHD?
It has not been tested. One paper proposed it as a candidate because of its effects on BDNF and dopamine in animals.
Keep reading
- Reset Your Brain's Reward System and Raise Your Dopamine Baseline.
- The Downfall of SSRI Drugs
- DNA,RNA and Protein synthesis as a metabolic processes
More guides:
Sources
- Tsai SJ Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Med Hypotheses 2007. PMID 16996699
- Asmarin IP, Nezavibat'ko VN, Miasoedov NF et al. A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study). Zh Vyssh Nerv Deiat Im I P Pavlova 1997. PMID 9173745
- Lebedeva IS, Panikratova YR, Sokolov OY et al. Effects of Semax on the Default Mode Network of the Brain. Bull Exp Biol Med 2018. PMID 30225715
- Dolotov OV, Karpenko EA, Seredenina TS 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. PMID 16635254
- Firstova IuIu, Dolotov OV, Kondrakhin eA et al. Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy. Eksp Klin Farmakol 2009. PMID 20095391
- Eremin KO, Kudrin VS, Saransaari P et al. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res 2005. PMID 16362768
- Kost NV, Sokolov OIu, Gabaeva MV et al. Semax and selank inhibit the enkephalin-degrading enzymes from human serum. Bioorg Khim 2001. PMID 11443939
- Miasoedova NF, Skvortsova VI, Nasonov EL et al. Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova 1999. PMID 10358912
- Gusev EI, Skvortsova VI, Miasoedov NF 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. PMID 11517472
- Gusev EI, Martynov MY, Kostenko EV 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. PMID 29798983
- Polunin GS, Nurieva SM, Baiandin DL et al. Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease. Vestn Oftalmol 2000. PMID 10741256
- Alekseeva GV, Bottaev NA, Goroshkova VV Use of semax at a follow-up of patients with posthypoxic encephalopathy. Anesteziol Reanimatol 1999. PMID 10199046
- Ivanikov IO, Brekhova ME, Samonina GE et al. Therapy of peptic ulcer with semax peptide. Bull Exp Biol Med 2002. PMID 12459874
- Manchenko DM, Glazova NIu, Levitskaia NG et al. Nootropic and analgesic effects of Semax following different routes of administration. Ross Fiziol Zh Im I M Sechenova 2010. PMID 21268834
- Vanhee C, Francotte A, Janvier S et al. The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind. Drug Test Anal 2020. PMID 31667971
- Sciacca MFM, Naletova I, Giuffrida ML et al. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models. ACS Chem Neurosci 2022. PMID 35080861
This guide is educational and is not medical advice. Talk to a qualified clinician before starting any compound, especially if you take medication, are pregnant, or compete in tested sport.