Cognitive Peptides: Semax, Selank and Nootropic Research

The area of cognitive peptides corresponds to the intersection between neuroscience and nootropic research. Semax and Selank are the two most studied cognitive peptides, both of which originated from Russia and have been approved for clinical use. This article will discuss published research related to cognitive peptides and in what ways the two different compounds are alike and different.

Nootropic Peptides in Published Research

What Qualifies as a Cognitive Peptide

Cognitive peptides, in regard to this directory, refers to substances being investigated for their capacity in producing cognitive effects in relation to enhancing cognitive operations or neuroprotective processes. So the term excludes the most frequently used nootropic products including such substances as racetams, choline-based products and all adaptogens that are not closely associated with studies of cognitive peptides. Semax and Selank are the only research substances referred to as peptides with cognitive effects significantly examined in the scientific literature.

Russian Clinical Heritage of Semax and Selank

Semax and Selank were invented at the Institute of Molecular Genetics of the Russian Academy of Sciences. In Russia, Semax has been approved since the 1990s for the treatment of stroke, cognitive dysfunction, and eye diseases. Selank is approved as an anxiolytic agent by Russian authorities. In Russia, there is a lot of clinical data available as a result of its utilization there, which gives us the sufficient amount of information on human safety and efficacy that is absent for many research peptides, although most of the data is published in Russian.

Semax: BDNF and Cognitive Research

Mechanism of Action

Semax is an artificial version of ACTH(4-10), a part of adrenocorticotropic hormone. The hypothesized mechanism of action implies the increase in the concentration of brain-derived neurotrophic factor (BDNF) that is responsible for the survival and growth of neurons as well as synaptic plasticity. Research indicates that Semax stimulates BDNF expression in the hippocampus and cortex of rats. It has been established that the low levels of BDNF are connected with depression, loss of cognitive abilities and neurodegenerative diseases.

Published Human Studies (Russian Literature)

Russian clinical studies on Semax report improvements in attention, memory and cognitive processing speed in stroke patients and individuals with cognitive impairment. A 2010 study in the Journal of Molecular Neuroscience examined Semax effects on BDNF and NGF expression in the rat brain. The clinical doses used in Russian practice are 200-600 mcg per day administered as a nasal spray, divided into 2-3 doses. These studies have generally small sample sizes and are not replicated in Western clinical settings.

NA-Semax-Amidate: The Modified Form

NA-Semax-Amidate is an advanced variant of Semax, which has an amide and an N-acetyl modification at the C-terminal end. These modifications intend to offer stability and efficacy by providing the peptide protection from breakdown by enzymes located in the nasal mucosa. PeptideGod markets NA-Semax-Amidate instead of the original form. There are fewer publications concerning NA-Amidate specific information compared to Semax, but the activities of the peptide are assumed to be similar.

Selank: Anxiolytic Peptide Research

Tuftsin-Based Structure

With Selank, the synthetic version of Tuftsin, one obtains an immunostimulatory agent that has features of an anxiolytic compound. Selank builds on Tuftsin in terms of its amino acid composition and demonstrates immunomodulatory and anxiety-relieving properties. The anxiolytic effect seems to involve changes in GABA and serotonin transmission. Animal experiments have shown a decrease in anxiety-like behavior measured through the elevated plus-maze and forced swimming tests with no sedative effect observed.

Anxiolytic and Immunomodulatory Data

The clinical data in Russia has mentioned anti-anxiety activity of Selank in individuals with generalized anxiety disorder, with the drug acting for several days after nasal intake. Selank was also studied for immune effects – modulation of interleukin expression and activity of immune cells. A 2006 study in Pharmacological Reports examined the anxiolytic effects of Selank in animal models. The combination of anti-anxiety and anti-immune activity makes Selank interesting to study.

Semax + Selank Combination

Rationale for Dual Administration

Semax is thought to promote the quantity and/or activity of BDNF in the brain, leading to improvements in cognitive function. Selank is supposed to promote relaxation through the pathways of GABA. The application of both peptides is of interest for researchers looking into ways of facilitating cognitive performance while reducing anxiety. Researchers working in this area can use Semax and Selank in combination, courtesy of PeptideGod offering ready-to-mix Semax + Selank nasal spray as well as the separate NA-Semax-Amidate medication. Nevertheless, there have been no studies empirically investigating the combined use of both peptides in a controlled way, although the established mechanisms justify their combined use.

Limitations of Nootropic Peptide Research

Language Barrier in Russian Studies

A large part of clinical studies of Semax and Selank is published in journals in the Russian language. Some studies are listed in PubMed, with English abstracts, but the full text is often not available in English. This leads to the verification problem for the Western researchers: the studies do exist, but they are difficult to evaluate properly.

Small Sample Sizes

Human studies undertaken with Semax and Selank have typically involved small sample sizes, resulting in studies that use a few dozen (typically 20-50) participants. In terms of modern clinical trials, the large sample sizes of this kind wouldn’t suffice to warrant high statistical power and enable the detection of rare adverse effects of the practices. So the studies provide only preliminary evidence as they wouldn't meet the standards of large multi-centered randomized controlled trials needed for FDA certification.