Semax Peptide: Memory and Cognition

Semax is a synthetic peptide with potential properties that include possible enhanced cognitive performance, reduction in mental fatigue, and increased neuroprotection. Because of this, it is often used in studies of nootropic peptides and within the context of improving cognitive function.

In an effort to review current research, our research team has produced this detailed guide, including our top choice for where to procure high-quality Semax. Click here to be redirected to Core Peptides.

What is Semax Peptide?

Semax is a manufactured version of the adrenocorticotropic hormone (ACTH)(4-10) fragment. In the 1980s, it was initially created by scientists at the Soviet Academy of Sciences. A Pro-Gly-Pro fragment attached to the heptapeptide’s C-terminus may support an ability to cross the blood-brain barrier (BBB) and enter the brain. Studies suggest that Semax may have stimulant-like effects on behavior, like ACTH(4-10), but possibly without affecting the CNS or the cardiovascular system.

Stroke, cognitive problems, optic nerve atrophy, and encephalopathy are some of the conditions within which Semax has been researched. Researchers hypothesize that the peptide may reach cognitive regions of the brain through extraneuronal transport from the olfactory epithelium via cranial nerves like the optic and trigeminal nerves.

The N-terminus of the molecule is acetylated, and the C-terminus is amidated to create the new molecule. This modification may improve the compound’s stability and efficacy compared to the unaltered form.

Semax Peptide: Mechanism of Action

It has been hypothesized that Semax might exert nootropic and neuroprotective effects through a diverse series of mechanisms. It has been suggested to be able to cross the blood-brain barrier (BBB) and potentially inducce dopamine and serotonin secretion.

Based on the results of one study, Semax was suggested as a central nervous system (CNS) agent for blocking the breakdown of enkephalins, the endogenous ligands of opioid receptors. As a result, the peptide may have a role in controlling pain perception and behavior motivated by rewards.

In addition, Semax seems to interact with molecules called neurotrophins, which are growth factors that control the survival, development, and functioning of neurons in the CNS and the PNS.

Semax has been speculated to increase BDNF and NGF, two important neurotrophic factors. There is also data suggesting that it may upregulate the expression of tropomyosin-related kinase B (trkB) receptors, which are found on the surface of brain cells and mediate the effects of brain-derived neurotrophic factors.

Findings imply that Semax appeared to have boosted BDNF levels by 60% in rats and trkB expression by 100% (twofold) in an experiment by Dolotov et al. (2006). Neuroprotective effects, decreased inflammation, and improved neuronal tolerance to hypoxia are all purported to result from BDNF and NGF activation.

Professionals have suggested that Semax may have potential that extends beyond the central nervous system. Semax has been explored for its speculated impact on ulcers, and for a positive impact on blood flow, microcirculation, and vascular permeability.

Semax Peptide Potential

Several prominant clinical studies exploring Semax are discussed here, the research findings of which suggest potential properties of this supplement within cognitive function, neuroplasticity, and neuroprotection.

Semax Peptide, Memory and Learning 

Semax has been suggested in clinical studies to contribute to maintaining cognitive stability and function. In one clinical trial, 16 adult subjects experiencing extreme fatigue were presented with Semax and subjected to a memory test. Compared to the placebo group, those given Semax peptide appeared to have performed much better on a memory test (71% correct vs. 41%). The findings of this experiment suggested a nootropic potential in the peptide, which appeared to last for at least 24 hours.

Resting-state functional magnetic resonance imaging (resting-state fMRI) also speculated that Semax may have increased the volume of certain areas of the central nervous system in test models. Brain regions involved in reward, emotional reactions, and decision making (medial frontal cortex) seemed to show significant differences under the influence of Semax versus a placebo solution.

Semax Peptide and the Brain

Semax has been hypothesized to exhibit neuroprotective potential, as posited from findings in animal research models of stroke. Data from studies suggests that it may be efficacious in decreasing inflammation, providing degrees of protection in radiation, mitigating hypoxia, and enhancing neurotrophic activity.

Semax was speculated to have significant anti-inflammatory impact in a trial of acute stroke research models. Interleukin-10 and tumor necrosis factor-alpha (TNF-alpha) production was purported to be increased by the peptide, whereas interleukin-8 and C-reactive protein levels were believed to be decreased.


[i] 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;68(5):1144-6. doi: 10.1016/j.mehy.2006.07.017. Epub 2006 Sep 25. PMID: 16996699.

[ii] Deigin, V. I., Poluektova, E. A., Beniashvili, A. G., Kozin, S. A., & Poluektov, Y. M. (2022). Development of Peptide Biopharmaceuticals in Russia. Pharmaceutics, 14(4), 716.

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[v] Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010 Jan;30(1):71-9. doi: 10.1007/s10571-009-9432-0. Epub 2009 Jul 25. PMID: 19633950

[vi] Dornbush, R. L., & Volavka, J. (1976). ACTH 4-10: a study of toxicological and behavioral effects in an aging sample. Neuropsychobiology, 2(5-6), 350– 360.

[vii] Manchenko, D. M., Glazova, N. I.u, Levitskaia, N. G., Andreeva, L. A., Kamenskiĭ, A. A., & Miasoedov, N. F. (2010). Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova, 96(10), 1014–1023.

[viii] Shevchenko, K. V., Nagaev, I. Y., Andreeva, L. A., Shevchenko, V. P., & Myasoedov, N. F. (2019). Prospects for Intranasal Delivery of Neuropeptides to the Brain. Pharmaceutical Chemistry Journal, 53, 89-100.

[ix] Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005 Dec;30(12):1493-500. doi: 10.1007/s11064- 005-8826-8. PMID: 16362768.

[x] Kost NV, Sokolov OIu, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA. Ingibiruiushchee deĭstvie semaksa i selanka na énkefalindegradiruiushchie fermenty syvorotki krovi cheloveka [Semax and selank inhibit the enkephalin-degrading enzymes from human serum]]. Bioorg Khim. 2001 May-Jun;27(3):180-3. Russian. doi: 10.1023/a:1011373002885. PMID: 11443939.