Semax (NA-Semax): Research, Mechanism & Current Evidence

What is Semax?

Semax is a synthetic peptide of seven amino acids based on a fragment of adrenocorticotropic hormone (ACTH), modified so that it no longer has the parent hormone's effect on the adrenal glands.

It was developed in Russia, where it has been a registered medicine since the 1990s and is used for stroke and cognitive indications. It has never been approved in the UK, EU or US.

What is Semax researched for?

Stroke recovery and traumatic brain injury are the clinical indications it is registered for in Russia.

Research interest outside that context centres on memory, attention and neuroprotection, and on BDNF — brain-derived neurotrophic factor, a protein involved in forming and maintaining connections between neurons.

• Improved short-term and working memory performance in fatigued individuals (71% vs 41% accuracy).
• Enhanced sustained attention during demanding cognitive tasks.
• Faster acquisition of new information and improved retention.
• Accelerated rehabilitation with increased BDNF levels in stroke patients.
• Supports recovery from traumatic brain injury.
• Shows anti-amyloid properties in Alzheimer's models.
• Supports neurogenesis through increased brain-derived neurotrophic factor.
• Enhanced neural connections and brain network activity.
• Improved ability to cope with cognitive stress.

How does Semax work?

The most consistently reported effect is increased expression of BDNF and its receptor TrkB in the hippocampus, the brain region most associated with memory formation.

Semax is usually studied intranasally rather than by injection, because peptides delivered into the nose can reach the brain along the olfactory and trigeminal nerves, partly bypassing the blood–brain barrier.

What does the research show?

There is a substantial Russian clinical literature spanning decades, including stroke trials. Animal and cell studies support the BDNF mechanism.

Independent Western replication is sparse, and few studies meet current international standards for randomisation, blinding and pre-registration.

Limitations of the current evidence

Long clinical use in one country is not the same as a robust evidence base. Much of the supporting literature is difficult to access, not peer-reviewed to international standards, or unavailable in English.

Modified variants sold as NA-Semax amidate have far less published research than Semax itself, despite being marketed as improved versions.

References

1. A Nootropic Adrenocorticotropin Analog 4-10 Semax: 15 Years Experience in Its Design and Study Ashmarin IP, Nezavibatko VN, Levitskaya NG, et al. Zhurnal Vysshei Nervnoi Deiatelnosti imeni I.P. Pavlova

   1997

   Foundational 15-year review: Semax stimulates operative memory and attention, increases hypoxia resistance, and improves brain circulation for 20-24 hours after intranasal doses of 0.015-0.050 mg/kg.

2. The Efficacy of Semax in the Treatment of Patients at Different Stages of Ischemic Stroke Gusev EI, Barskov IV, et al. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova

   2018

   110 patients after ischemic stroke; Semax (6000 mcg/day intranasal) increased BDNF plasma levels, sped functional recovery, and improved motor performance during rehabilitation.

   Controlled clinical trial

3. Effects of Semax on the Default Mode Network of the Brain

   Lebedeva IS, Panikratova YR, Sokolov OY, et al. · Bulletin of experimental biology and medicine · 2018

   24 healthy volunteers (43.9 +/- 9.5 years); resting-state fMRI showed increased default mode network volume in medial frontal cortex after intranasal 1% Semax vs placebo.

   Early human study · PMID 30225715

4. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

   Medvedeva EV, Dmitrieva VG, Povarova OV, et al. · BMC genomics · 2014

   Genome-wide study of ischemized rat brain cortex: Semax modulated expression of 24 vascular genes at 3h and enhanced immune-response gene expression at 24h post-pMCAO, including immunoglobulin and chemokine groups.

   Animal study · PMID 24661604

5. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus

   Dolotov OV, Karpenko EA, Inozemtseva LS, et al. · Brain research · 2006

   Single application at 50 mcg/kg produced 1.4-fold increase in BDNF protein and 1.6-fold increase in trkB tyrosine phosphorylation in rat hippocampus.

   Animal study · PMID 16996037

6. [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]

   Gusev EI, Martynov MY, Kostenko EV, et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2018

   PMID 29798983

7. [A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)]

   Asmarin IP, Nezavibat'ko VN, Miasoedov NF, et al. · Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova · 1997

   PMID 9173745

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