Semax and Selank: BDNF Upregulation vs GABAergic Anxiolysis

Updated 8 September 2026

Editorial note: this article summarises published research on Semax and Selank. Baclabs does not sell Semax, Selank or any peptide; we supply bacteriostatic water and reconstitution consumables. Nothing here is medical advice.

Semax and Selank are two Russian regulatory peptides that are frequently discussed together, and just as frequently confused. They share a design principle, a natural peptide fragment stabilised with a C-terminal Pro-Gly-Pro tail, and both are registered in Russia as intranasal drugs. But they do different things. Semax is pitched as a nootropic acting through neurotrophic signalling; Selank is pitched as an anxiolytic acting through GABAergic and enkephalin pathways. This article sets out what each one is, what the published evidence shows, and why the popular “semax and selank stack” idea needs a careful caveat.

Both are unlicensed in the UK and neither is an injectable in its registered form. Those two facts shape everything that follows.

What Semax is and how it is thought to work

Semax is a heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues correspond to the ACTH(4-7) fragment of adrenocorticotropic hormone, the melanocortin sequence stripped of the hormone’s steroidogenic activity, and the trailing Pro-Gly-Pro slows enzymatic degradation, extending the peptide’s action. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and is registered there as intranasal drops in 0.1% and 1% strengths.

The mechanism that draws most attention is neurotrophic. In rat hippocampus, a single dose of Semax (50 µg/kg) increased brain-derived neurotrophic factor (BDNF) protein roughly 1.4-fold and TrkB receptor tyrosine phosphorylation roughly 1.6-fold, with larger rises in the messenger RNA for both [1]. BDNF and its receptor TrkB are central to synaptic plasticity, so raising their expression is a plausible route to the reported effects on attention and memory. Separate work shows Semax binds in the basal forebrain and raises BDNF there [2], and describes activation of neurotrophin and receptor transcription after experimental cerebral ischaemia [3].

Semax and stroke: the human data

Semax’s most cited clinical use is in acute ischaemic stroke, where it is given in Russia as part of combined therapy. One study tracked plasma BDNF, motor performance and Barthel index in stroke patients and reported that semax and higher BDNF levels accelerated functional improvement [4]. An earlier clinical and electrophysiological study in 30 patients in acute hemispheric ischaemic stroke reported an influence on recovery rate [5].

These are real publications, but the evidence has limits: samples are small, most work is Russian-language and single-region, and independent replication outside Russia is scarce. Semax is further along than most peptides in this cluster, without being an established treatment by Western regulatory standards.

What Selank is and how it is thought to work

Selank is a heptapeptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro, based on the immunomodulatory peptide tuftsin and again carrying the stabilising Pro-Gly-Pro tail. It was developed by the same Institute of Molecular Genetics with the Zakusov Institute of Pharmacology and is registered in Russia as 0.15% intranasal drops.

Where Semax targets neurotrophins, Selank targets anxiety circuits. It behaves as a positive modulator of GABA binding, affecting the expression of genes involved in GABAergic neurotransmission, and it inhibits enkephalin-degrading enzymes, which may prolong the action of endogenous enkephalins [6]. That combination is offered as the explanation for a benzodiazepine-like calming effect without the classic sedation and dependence profile.

Selank and anxiety: the human data

The clinical case for Selank rests on Russian comparative trials. In one study, Selank in 30 patients was compared with the benzodiazepine medazepam in 32 patients with generalised anxiety and neurasthenia; the anxiolytic effects were similar, but Selank also showed antiasthenic and mild psychostimulant effects [7]. A separate comparison of Selank against phenazepam in 60 patients with phobic-anxiety and somatoform disorders reported pronounced anxiolytic and mild nootropic effects, with the anxiolytic benefit persisting for about a week after the last dose and a favourable tolerability profile [8]. Preclinical work reports the peptide completed phase-3 clinical testing in Russia [6].

Semax versus Selank at a glance

Feature Semax Selank
Sequence Met-Glu-His-Phe-Pro-Gly-Pro Thr-Lys-Pro-Arg-Pro-Gly-Pro
Parent molecule ACTH(4-7) fragment Tuftsin
Proposed mechanism BDNF/TrkB neurotrophic signalling GABAergic modulation, enkephalinase inhibition
Marketed use Nootropic; stroke recovery Anxiolytic; anti-stress
Registered form Intranasal drops (Russia) Intranasal drops (Russia)
Strongest human data Ischaemic stroke studies [4][5] Anxiety comparisons vs benzodiazepines [7][8]
UK status Unlicensed Unlicensed

The “semax and selank stack” idea

Because the two peptides target different systems, online sources often describe a semax and selank stack, Semax for focus, Selank for calm. This combination has not been validated in controlled human trials as a stack; the clinical publications studied each peptide separately for its own indication. A functional-connectivity study did examine both peptides’ effects on resting-state brain networks in 52 healthy participants, but that is a mechanistic imaging study, not evidence that co-administration is safe or effective for cognitive enhancement [9]. Treat the stack as an extrapolation, not a tested protocol.

The intranasal route and preparation notes

A point that vendors routinely blur: Semax and Selank are intranasal products, not injectables. The registered Russian medicines are nasal drops, and the human evidence above was generated by nasal, not subcutaneous, delivery. Powder sold for reconstitution is sometimes marketed for injection, but that is not how these peptides were studied.

For nasal preparation, diluent choice is the practical question. The benzyl alcohol in bacteriostatic water is an effective preservative but can irritate the nasal mucosa, so preservative-free 0.9% saline is often chosen for nasal use; the trade-off is set out in bacteriostatic versus sterile water. Where a preserved multi-dose vial is appropriate, Baclabs supplies UK-stocked bacteriostatic water in 30 mL vials, and the reconstitution guide covers the concentration maths. Once punctured, a bacteriostatic vial is generally treated as usable for up to 28 days if stored correctly, see storage and shelf life. For related bioregulator dosing questions, see Epithalon and Pinealon, and for the wider picture the cognitive peptides pillar.

Frequently asked questions

What is the difference between Semax and Selank?

Semax is an ACTH(4-7)-derived heptapeptide acting through BDNF/TrkB neurotrophic signalling and marketed as a nootropic, with Russian stroke studies behind it [1][4]. Selank is a tuftsin-derived heptapeptide acting through GABAergic modulation and marketed as an anxiolytic, with Russian anxiety trials behind it [7][8]. Different sequences, different mechanisms, different intended uses.

Are Semax and Selank injected or used in the nose?

Both are registered in Russia as intranasal drops, and the clinical evidence was generated with nasal delivery. They are not injectable medicines in their registered form. Vendors selling powder “for reconstitution” are offering something outside how the peptides were actually studied.

Is the semax and selank stack safe?

There is no controlled human trial of the combination as a stack. The clinical studies tested each peptide separately. A functional-imaging study looked at both in healthy volunteers, but that does not establish that co-use is safe or effective for cognitive enhancement [9]. The safety of combined, long-term use is simply unknown.

Are Semax and Selank legal in the UK?

Neither holds a UK marketing authorisation, so neither can be sold or supplied as a medicine under the Human Medicines Regulations 2012 [10]. Products sold as “research chemicals” sit outside the licensed system, with no regulated quality or safety oversight.

Should Semax or Selank be mixed with bacteriostatic water?

For nasal use, benzyl alcohol can irritate the nasal lining, so preservative-free saline is often preferred; bacteriostatic water is the choice where a preserved multi-dose vial is needed. The decision is about the route and how long the vial will be in use, see our diluent comparison for the trade-offs.

References

  1. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research, 2006
  2. Semax, an analogue of ACTH(4-10), binds specifically and increases BDNF protein in rat basal forebrain. Neurosci Lett, 2006
  3. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. 2024
  4. The efficacy of semax in the treatment of patients at different stages of ischemic stroke. Zh Nevrol Psikhiatr, 2018
  5. Effectiveness of semax in acute period of hemispheric ischemic stroke. Zh Nevrol Psikhiatr, 2001
  6. Peptide-based anxiolytics: the molecular aspects of heptapeptide Selank biological activity. Curr Pharm Des, 2018
  7. Efficacy and possible mechanisms of action of the peptide anxiolytic selank in generalized anxiety and neurasthenia. Zh Nevrol Psikhiatr, 2008
  8. A comparison of the anxiolytic effect and tolerability of selank and phenazepam in anxiety disorders. Zh Nevrol Psikhiatr, 2014
  9. Functional connectomic approach to studying Selank and Semax effects. 2020
  10. The Human Medicines Regulations 2012, regulation 46. legislation.gov.uk


Disclaimer: This content is for educational purposes only and does not constitute medical advice. Bacteriostatic water is supplied for reconstitution of substances intended for research and for use as directed by a healthcare professional. Peptides and medicines discussed here may be unlicensed in the UK or prescription-only; consult a qualified clinician before using any medicine. Baclabs does not sell peptides.