Semax and Selank are synthetic peptide nootropics developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. Both were approved as prescription medications in Russia in the 1990s and have been used clinically for over 25 years. They represent two of the most well-characterised nootropic peptides in existence.
For the broader context of Russian cognitive peptide research, see our dedicated article.
Semax
What Is Semax?
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) based on the ACTH(4-10) fragment. It was developed in the 1980s by Professor Nikolai Myasoedov and approved in Russia for the treatment of stroke, cognitive impairment, and peptic ulcers. It is administered intranasally.
Mechanism of Action
- BDNF upregulation: Semax increases brain-derived neurotrophic factor (BDNF) expression by 2-8x in rodent models (Dolotov et al., Brain Research, 2006). BDNF supports neuronal survival, synaptogenesis, and long-term potentiation.
- NGF upregulation: Increases nerve growth factor expression in the hippocampus and basal forebrain.
- Dopamine modulation: Enhances dopaminergic and serotonergic neurotransmission in the prefrontal cortex.
- Neuroprotection: Protects against oxidative stress and excitotoxicity in ischaemic brain models.
Variants Studied
Semax is studied alongside modified analogues (N-Acetyl Semax and N-Acetyl Semax Amidate) developed for improved stability and blood-brain barrier penetration. Dose, frequency and route guidance is outside the scope of research-use-only material.
Selank
What Is Selank?
Selank is a synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) based on the endogenous immunomodulatory peptide tuftsin with a Pro-Gly-Pro stabilisation sequence. Approved in Russia as an anxiolytic and nootropic, it targets anxiety, cognitive impairment, and immune function.
Mechanism of Action
- GABA modulation: Selank enhances GABAergic neurotransmission, producing anxiolytic effects comparable to benzodiazepines but without sedation, dependence, or withdrawal (Seredenin et al., 1998).
- Enkephalin stabilisation: Inhibits enkephalin degradation, increasing endogenous opioid peptide levels and promoting stress resilience.
- IL-6 modulation: Normalises interleukin-6 levels, providing anti-inflammatory and immunomodulatory effects.
- Serotonin metabolism: Influences serotonin metabolism in the frontal cortex, contributing to mood stabilisation.
Variants Studied
Selank is studied alongside modified analogues (N-Acetyl Selank and N-Acetyl Selank Amidate) developed for improved stability and blood-brain barrier penetration. Dose, frequency and route guidance is outside the scope of research-use-only material.
Semax + Selank Together
The combination is the most frequently discussed nootropic peptide pairing in the research literature. Semax is associated with cognitive stimulation and focus (via BDNF and dopamine), while Selank is associated with anxiolytic effects without sedation (via GABA and enkephalins). The mechanisms are complementary rather than overlapping.
Dosing, timing and cycling guidance is outside the scope of research-use-only material.
Side Effects
Both peptides have established safety profiles based on decades of clinical use in Russia:
- Semax: Nasal dryness, mild headache (rare), temporary insomnia if dosed late in the day
- Selank: Nasal irritation, fatigue at higher doses (rare)
No dependence, tolerance, or withdrawal effects have been reported with either peptide in clinical literature.
Comparison to Other Nootropics
For those interested in the broader nootropic landscape, see our cognitive supplement stack which covers non-peptide options including lion's mane, alpha-GPC, and phosphatidylserine.
Key References
- Dolotov, O.V. et al. (2006). "Semax, an analog of ACTH(4-10), stimulates the expression of BDNF in the rat hippocampus." Doklady Biological Sciences, 407, 148-151.
- Seredenin, S.B. et al. (1998). "Anxiolytic properties of Selank." Bulletin of Experimental Biology and Medicine, 125(5), 497-499.
- Eremin, K.O. et al. (2004). "Selank effects on the expression of genes encoding GABA receptor subunits." Bulletin of Experimental Biology and Medicine, 137(5), 444-447.