Semax

Semax is a synthetic heptapeptide, which means it is a short chain of seven amino acids (Met-Glu-His-Phe-Pro-Gly-Pro). It is derived from a fragment of the adrenocorticotropic hormone, known as ACTH(4-7). Thanks to a targeted molecular tweak, Semax no longer has any hormonal activity on the adrenal cortex, but it keeps its neuroprotective and cognition-enhancing properties. The peptide was developed at the Moscow Institute of Molecular Genetics and has been approved in Russia as a nasal spray since 1994 [1,2].

How is Semax used?

Medically, Semax is mainly given intranasally, meaning it is sprayed or dropped into the nose and absorbed through the nasal mucosa. In Russia, two finished drug concentrations are approved: a 0.1% solution for cognitive applications and a higher-dose 1% solution for acute neurological conditions such as stroke [2]. All available clinical human studies have only looked at this nasal route of administration.

On the international gray market, Semax is often sold as a lyophilized (freeze-dried) peptide powder in vials of 5 mg or 10 mg, which some people inject subcutaneously after mixing it with a liquid. There is no scientifically proven safety basis for injections: in 2024, the US Food and Drug Administration (FDA) stated that it could not find a single human study on the subcutaneous use of Semax [9]. In addition, unregulated sources lack testing for purity, identity, and sterility - the guide on protection when ordering explains what users should look out for.

From vial to use: mixing Semax as a nasal spray

Reconstituting lyophilized Semax powder for intranasal self-medication is an unregulated practice without any official medical dosing recommendation. The following example calculation only illustrates the mathematical derivation of the active ingredient concentration per spray.

Example with 5 mg Semax powder:

• If you dissolve 5 mg of Semax dry powder in 5 ml of BAC water (bacteriostatic water), you get a 0.1% solution with a concentration of exactly 1 mg/ml.
• A standard spray from a nasal spray atomizer releases about 0.1 ml of solution, which mathematically corresponds to a dose of 100 µg of Semax per spray.
• Taking 2-3 sprays per nostril delivers 200-300 µg of active ingredient, which matches the application range of the Russian 0.1% original product [2].

For a high-concentration 1% solution according to the Russian stroke protocol, 5 mg of Semax powder is dissolved in 0.5 ml of BAC water, so that a 0.1 ml spray delivers around 1,000 µg of peptide. You can find step-by-step details on reconstitution and shelf life in the instructions. Since the peptide is heat-sensitive, storage requires constant cooling at 2-8 °C, protected from heat and frost.

How does Semax work in the brain?

Semax works in the central nervous system through two main pathways: it activates the melanocortinergic and serotonergic neurotransmitter systems, and it boosts the production of neurotrophic factors, which are proteins that help nerve cells grow and survive. As a synthetic fragment of ACTH(4-7), the heptapeptide was modified so that it lost its hormonal activity but still activates those two neurotransmitter systems.

A key neurobiological effect of Semax is the increase of Brain-Derived Neurotrophic Factor (BDNF) in the hippocampus, a brain region important for memory. This signaling protein regulates the survival of nerve cells, synaptic plasticity (how connections between neurons strengthen or weaken), and neurogenesis (the birth of new neurons). Because Semax works through changes in gene expression, the neuroprotective effects last for many hours, even though the plasma half-life of the peptide in the bloodstream is only a few minutes [1,3].

What is proven in human studies?

The most well-known clinical study on Semax's effect in acute ischemic stroke was published by Gusev and colleagues in 2018, involving 110 stroke patients. Treatment consisted of two 10-day cycles with 6,000 µg of Semax intranasally daily, with a 20-day therapy break in between. After five months of observation, the subjects showed improved scores on the Barthel Index for daily living skills, on the MRC scale for muscle strength, and had higher BDNF plasma levels [4]. However, because the study lacked randomization and blinding, its conclusiveness is methodologically limited.

In its 2024 scientific review, the FDA analyzed all published human evidence on Semax and concluded that no human pharmacokinetic studies for Semax existed. The available data was limited to 33-47 healthy subjects, 69 adults with pre-existing conditions, and 451 pediatric patients with tic disorders or depression, with most studies not being placebo-controlled [9].

What do animal and cell studies show?

In preclinical in-vitro and animal models, Semax shows versatile neuroprotective, antidepressant, anti-inflammatory, and pain-relieving effects [5,6]. A comparative study in rats also showed that intranasal administration promoted cognitive learning processes significantly more than intraperitoneal injection, highlighting the efficiency of direct drug uptake through the olfactory mucosa [8].

An animal Alzheimer's study on APP/PS1 mice from 2024 documented a measurable reduction of amyloid-beta plaques in the brain after intranasal administration of Semax (50 µg/kg every other day for four weeks). At the same time, results in the Barnes maze and in object recognition tests improved [10]. These findings offer valuable basic clues, but they cannot be directly transferred to human therapies.

Semax vs. Selank - what's the difference?

Semax and Selank are closely related Russian heptapeptides for intranasal application, but they target different goals: Semax is mainly for neuroprotection, cognitive enhancement, and attention, while Selank primarily has anxiolytic, stress-reducing, and mood-lifting effects. The direct peptide comparison on Selank & Semax offers a detailed side-by-side look at the effect profiles, dosages, and indications of both nootropics.

Is Semax safe?

According to the official Russian drug information, Semax is contraindicated in cases of hypersensitivity, acute mental disorders, anxiety disorders, pregnancy, breastfeeding, a history of seizures, and in people under 18 years of age [2]. In preclinical safety and toxicity tests, no mutagenic, toxic, or fetal-damaging effects occurred.

The US FDA summarized its safety assessment of Semax in 2024 in four key points [9]:

• There are no systematic human safety studies for subcutaneous injection, since medical research almost exclusively covered nasal administration.
• In individually compounded peptide preparations, there is an increased immunogenicity risk due to peptide aggregation and chemical impurities.
• The FDA's FAERS surveillance system contains a case report of severe eye irritation and burning with hospital admission after using an online-purchased 0.1% Semax product.
• The majority of Russian publications only incompletely recorded adverse side effects, which makes it difficult to assess rare risks.

Legal status

In Russia, Semax has been registered as a marketable finished drug since 1994 and is on the national list of essential medicines [1,2]. Neither the US FDA nor the European EMA has approved it as a drug so far.

As part of the 2024/2026 evaluation for the US 503A bulks list for compounding drugs, FDA experts advised against releasing Semax for compounding pharmacies, since Semax did not convince on any of the four criteria - chemical characterization, historical compounding use, effectiveness, and safety [9]. Despite a positive vote in the advisory PCAC committee (Pharmacy Compounding Advisory Committee) in July 2026, Semax remains without official approval in the US, and there are no officially validated dosing regimens for healthy users.

What is still unknown?

For a final evidence-based assessment of Semax, placebo-controlled double-blind studies according to Western standards are currently missing. Most of the existing knowledge is based on Russian open-label studies; solid long-term safety data for Western or ethnically diverse patient populations is not available.

Furthermore, the FDA highlighted in 2024 that no validated human pharmacokinetic data exists for Semax [9]. How much Semax actually reaches the blood or brain after nasal administration, via which metabolic pathways the peptide is broken down in the human body, and what danger potential exists with subcutaneous injection, is scientifically unclear. The peptide library offers systematic overviews of other active ingredients.