Semax + Selank Cognitive Stack:
Research Protocol Guide

Semax: ACTH Analogue and BDNF Driver

Semax is a heptapeptide analogue of the N-terminal fragment of ACTH (4-10) with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. Unlike ACTH, it lacks adrenal stimulatory activity, but retains and enhances the cognitive and neuroprotective effects of the parent molecule. Key published mechanisms include BDNF and NGF upregulation in the hippocampus, serotonin and dopamine system modulation, and antioxidant activity in ischaemic injury models.

Russian clinical data, largely published in Soviet-era neurological journals, describes Semax use in stroke rehabilitation, attention deficit conditions, and cognitive decline. It is registered as a pharmaceutical in Russia and Ukraine for cognitive impairment and ischaemic stroke, giving it an unusually well-characterised clinical safety profile for a research peptide.

Selank: Anxiolytic via GABA and Enkephalin Pathways

Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic heptapeptide based on the immunomodulatory peptide tuftsin. Its primary anxiolytic mechanism involves positive allosteric modulation of GABA-A receptors, producing effects comparable to benzodiazepines in rodent anxiety models without the sedation, tolerance, or dependence pharmacology of classical GABAergic drugs. Selank also upregulates BDNF and enkephalin gene expression, contributing to mood stabilisation and memory consolidation effects.

Like Semax, Selank is registered as a pharmaceutical anxiolytic in Russia and Ukraine, meaning it has passed formal regulatory review. The published human safety data, though limited in sample size and published primarily in Russian journals, consistently shows a benign adverse event profile.

Mechanistic Synergy

The pairing addresses two common research objectives simultaneously: cognitive enhancement (via Semax's BDNF/ACTH activity) and anxiety reduction (via Selank's GABA modulation). In practice, Semax's stimulating ACTH-like activity can produce mild agitation in some subjects at higher doses; Selank's anxiolytic activity provides a counterbalancing effect. The combined BDNF upregulation from both peptides is the most cited mechanistic rationale for their co-use.

Intranasal Administration Protocol

Both peptides are typically administered intranasally in Russian clinical practice, allowing direct transport via the olfactory nerve pathway with reduced systemic dilution. Common research concentrations:

• Semax: Reconstitute 30mg in 3mL bacteriostatic water = 10mg/mL. A 100 mcg dose = 0.01mL ≈ 1 drop. Standard research doses: 200–600 mcg per administration, once or twice daily
• Selank: Reconstitute 5mg in 5mL bacteriostatic water = 1mg/mL. A 250 mcg dose = 0.25mL. Standard: 250–500 mcg twice daily
• Both administered via nasal dropper or spray, alternating nostrils

Cycling

• Standard cycle: 2 weeks on, 1 week off (to prevent potential receptor adaptation)
• Or: 5 days on, 2 days off (weekday dosing, matching Russian clinical practice)
• Some protocols run 4–6 weeks continuously without washout in clinical data

Extension: Dihexa Addition

The intermediate Focus & Neuroprotection Stack adds Dihexa (oral, 10–15 mg/day) to target HGF/MET pathway-mediated synaptogenesis. Dihexa is structurally derived from angiotensin IV and has demonstrated synaptogenic activity approximately 10 million times more potent than BDNF in direct comparison studies (McCoy et al., 2013, Washington State University). Its oral bioavailability makes it a convenient complement to the intranasal Semax/Selank protocol.