Selank Clinical Research: Russian Trial Analysis

Selank is a synthetic heptapeptide developed entirely within Russian research institutions — first at the Institute of Molecular Genetics of the Russian Academy of Sciences, then studied at the V.V. Zakusov Research Institute of Pharmacology. In 2009, the Russian Ministry of Health approved it as a prescription anxiolytic nasal spray for generalized anxiety disorder (GAD).

That approval was based on a series of clinical trials conducted exclusively in Russia. These trials compared Selank to established benzodiazepines, tested it as an adjunctive therapy, and examined its neurophysiological effects using EEG monitoring.

For researchers and clinicians outside Russia, evaluating this evidence means working through language barriers, limited Western replication, and study designs that sometimes differ from FDA or EMA standards. This review examines the actual trial data — what was measured, how many patients were studied, what the outcomes showed, and where the evidence has gaps.

Table of Contents

• What Is Selank?
• The GAD vs. Medazepam Trial (Zozulya et al., 2008)
• Rapid vs. Slow Responders: EEG Study
• The Phenazepam Combination Trial
• Mechanisms of Action: What the Preclinical Data Shows
• Immunomodulatory and Antiviral Research
• Comparison Table: Selank vs. Benzodiazepines in Clinical Trials
• Limitations of the Current Evidence
• FAQ
• The Bottom Line
• References

What Is Selank?

Selank (sequence: Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a modified analog of tuftsin, a naturally occurring tetrapeptide (Thr-Lys-Pro-Arg) found within the heavy chain of human immunoglobulin G. Researchers at the Institute of Molecular Genetics extended tuftsin's C-terminus with three amino acids — Pro-Gly-Pro — to improve metabolic stability and extend its duration of action [1].

The result is a peptide with dual properties: anxiolytic activity affecting the central nervous system and immunomodulatory activity inherited from its tuftsin backbone.

Selank is administered intranasally (as a 0.15% nasal spray), which allows absorption through the nasal mucosa and access to the CNS via olfactory and trigeminal nerve pathways. This bypasses first-pass liver metabolism, a practical advantage for peptides that would be broken down in the GI tract.

The standard clinical dosing in Russian trials has been 900 mcg per administration, typically given three times daily (total daily dose: 2,700 mcg) over treatment periods of 14 days.

The GAD vs. Medazepam Trial (Zozulya et al., 2008)

This is the most frequently cited Selank clinical trial and the primary study supporting its anxiolytic efficacy [2].

Study Design

• Population: 62 patients diagnosed with GAD and neurasthenia
• Design: Open-label, active-comparator (not placebo-controlled)
• Groups: Selank (n=30) vs. medazepam (n=32)
• Duration: 14 days of treatment
• Route: Selank was given intranasally; medazepam was given orally
• Assessment tools: Hamilton Anxiety Rating Scale (HARS), Zung Self-Rating Anxiety Scale, Clinical Global Impression (CGI) scale

Clinical Outcomes

The anxiolytic effect of Selank was comparable to that of medazepam across all three rating scales. Both groups showed statistically significant reductions in anxiety symptoms over the 14-day treatment period.

But the two drugs differed in their secondary effects. Selank produced what the authors described as "antiasthenic and psychostimulant effects" — patients reported improved energy and reduced mental fatigue alongside anxiety relief. Medazepam, a benzodiazepine, did not produce these effects and was associated with the typical sedation profile of its drug class.

Biological Marker: Enkephalin Degradation

The study also measured enkephalin degradation rates in blood serum (specifically, the half-life of leu-enkephalin, expressed as tau 1/2). At baseline, patients with GAD and neurasthenia had decreased leu-enkephalin half-lives — meaning their enkephalins were being broken down faster than normal. This correlated with disease duration, symptom severity, and autonomic disturbance.

During Selank treatment, leu-enkephalin half-life increased — particularly in GAD patients — suggesting the peptide may stabilize endogenous opioid peptides by inhibiting the enzymes that degrade them. This effect was not observed (or not measured) in the medazepam group.

Strengths and Limitations

The 62-patient sample and active-comparator design provide useful efficacy signals. However, the open-label design (both patients and clinicians knew which drug was being administered) introduces potential bias. The absence of a placebo arm makes it impossible to separate drug effects from natural symptom fluctuation or placebo response, both of which are substantial in anxiety disorder research.

Rapid vs. Slow Responders: EEG Study

A separate study examined individual variability in treatment response to Selank, using both clinical scales and quantitative EEG monitoring [3].

Study Design

• Population: 20 patients aged 24–52 with DSM-IV-diagnosed GAD
• Dose: 2,700 mcg/day intranasally
• Assessment: HARS + pharmaco-EEG (single-dose EEG response measured after 900 mcg)

Clinical Outcomes

The study identified two distinct response patterns:

Rapid responders (40% of patients): HARS total score dropped from 20.3 to 7.0 within 3 days of starting treatment (p < 0.01). This is a clinically significant reduction — a score below 7 generally indicates minimal anxiety.

Conventional responders (60% of patients): HARS total score dropped from 16.1 to 6.2 by Day 14 (p < 0.01). The end-point scores were similar between groups, but conventional responders required the full two-week treatment course.

EEG Findings

Rapid responders showed a measurable EEG shift after a single 900 mcg dose:

• Increased beta-rhythm power (associated with alertness and cognitive processing)
• Decreased theta-rhythm and low-frequency alpha-rhythm power (patterns often elevated in anxiety states)
• All changes reached statistical significance (p < 0.05)

Conventional responders did not show these acute EEG changes. At baseline, rapid responders had higher scores for asthenic and cognitive symptoms compared to conventional responders, suggesting that patients with more prominent fatigue and cognitive complaints may be more likely to respond quickly.

Significance

This study is small (n=20) and uncontrolled, but it introduces two important ideas. First, Selank's effects may be detectable through objective neurophysiological measures (EEG), not just subjective rating scales. Second, baseline symptom profiles may predict who responds fastest — a finding that would have clinical relevance if replicated in larger samples.

The Phenazepam Combination Trial

A clinical study tested whether adding Selank to standard phenazepam (a potent Russian benzodiazepine) treatment could improve outcomes and reduce side effects in anxiety-spectrum disorders [4].

Study Design

• Population: 70 patients with anxiety-phobic, hypochondriac, and somatoform disorders (ICD-10: F40.2-9, F41.1-9, F45.0-2)
• Groups: Phenazepam monotherapy (n=30) vs. phenazepam + intranasal Selank (n=40)
• Assessment tools: HDRS, CGI, Spielberger anxiety scales, UKU side-effect scale
• Cognitive testing: Stroop test and verbal fluency test
• Quality of life: SF-36 questionnaire

Clinical Outcomes

Patients receiving the combination achieved clinical improvement faster (earlier reduction in HDRS scores) compared to phenazepam alone. But the more notable finding was the side-effect profile.

The combination group showed reduced severity of several common phenazepam side effects:

• Attention and memory impairment
• Asthenia (fatigue/weakness)
• Sedation and excessive sleep duration
• Emotional indifference
• Orthostatic hypotension
• Sexual disturbances

These reductions were observed both during active treatment and after phenazepam withdrawal. On cognitive testing, the combination group performed better on the Stroop test and verbal fluency measures — suggesting Selank's nootropic properties may directly counteract benzodiazepine-induced cognitive impairment.

SF-36 quality-of-life scores reflected these differences, with the combination group reporting better overall outcomes.

Clinical Implications

If replicated, these findings suggest Selank could function as an adjunctive therapy that makes benzodiazepine treatment more tolerable — allowing the anxiolytic benefits while reducing the cognitive and functional costs. This has practical relevance given that benzodiazepine side effects are a major driver of treatment discontinuation in anxiety disorders.

Mechanisms of Action: What the Preclinical Data Shows

Russian preclinical research has identified several molecular pathways through which Selank appears to exert its effects.

GABAergic System Modulation

Researchers at the Russian Academy of Sciences analyzed expression of 84 genes involved in neurotransmission in the frontal cortex of rats after administration of Selank or GABA (300 mcg/kg). Within 1 hour, 45 of 84 genes showed significant expression changes. At 3 hours, 22 genes had altered expression. The expression profiles of Selank and GABA showed positive correlation, supporting the idea that Selank acts partly through GABAergic mechanisms [5].

This is consistent with clinical observations that Selank produces anxiolytic effects resembling low-dose benzodiazepines — which work by enhancing GABA-A receptor inhibition — without causing sedation, dependence, or cognitive impairment.

Serotonin Metabolism

In Wistar rats pretreated with the serotonin synthesis inhibitor PCPA, Selank increased serotonin metabolism in the brain stem within 30 minutes of injection. Native tuftsin (the parent peptide) did not produce this effect in the brain stem and actually decreased serotonin metabolism in the neocortex [6]. This suggests the Pro-Gly-Pro extension gives Selank distinct neurochemical properties beyond those of tuftsin alone.

BDNF Upregulation

Selank has been shown to rapidly increase brain-derived neurotrophic factor (BDNF) mRNA expression in the rat hippocampus [6]. BDNF plays a central role in neuroplasticity, memory formation, and stress resilience. Its upregulation may explain both the anxiolytic and nootropic effects observed in clinical studies. This BDNF connection also places Selank alongside compounds like Semax in the broader category of peptides with potential cognitive enhancement applications.

Enkephalin Stabilization

As noted in the Zozulya et al. clinical trial, Selank appears to inhibit enzymes that degrade endogenous enkephalins. Preclinical work showed Selank was more potent than established peptidase inhibitors (bacitracin and puromycin) at suppressing enkephalin hydrolysis [2]. By prolonging enkephalin half-life, Selank may support endogenous opioid tone without directly activating opioid receptors — a mechanism distinct from both benzodiazepines and traditional anxiolytics.

Immunomodulatory and Antiviral Research

Selank's tuftsin backbone gives it immunological properties that go beyond its CNS effects.

Antiviral Activity

A study by Ershov et al. (2009) tested Selank against influenza A virus (H3N2 strain) both in vitro and in vivo. When added to cell cultures 24 hours before viral inoculation, Selank completely suppressed viral reproduction. In animal models, preventive administration produced the highest survival rates [7].

Further work identified antiviral activity against influenza B (Ohio strain), avian influenza H5N1, herpes simplex virus types 1 and 2, cytomegalovirus, and murine encephalomyocarditis virus. The tetrapeptide fragment Arg-Pro-Gly-Pro showed the highest antiviral potency among Selank's structural fragments.

The proposed mechanism involves upregulation of interferon-alpha (IFN-alpha) gene expression without affecting IL-4, IL-10, or TNF-alpha, suggesting selective modulation of the Th1/Th2 cytokine balance [7].

Cytokine Modulation in Anxiety Patients

In patients with anxiety-asthenic disorders, Selank treatment over 14 days shifted the Th1/Th2 cytokine balance in serum. The peptide also suppressed IL-6 gene expression in peripheral blood cells of patients with depression — an effect not seen in healthy controls [8]. Elevated IL-6 has been consistently linked to depression and anxiety in the broader psychiatric literature, making this a potentially relevant finding.

Comparison Table: Selank vs. Benzodiazepines in Clinical Trials

Parameter	Selank	Benzodiazepines (medazepam/phenazepam)
Anxiolytic efficacy	Comparable (HARS, Zung, CGI)	Established
Onset of effect	1–3 days (rapid responders); ~14 days (typical)	Hours to days
Sedation	Not observed	Common
Cognitive impairment	Not observed; possible nootropic effect	Common (attention, memory)
Dependence/withdrawal	Not observed	Well-documented risk
Effect on energy/fatigue	Antiasthenic (reduces fatigue)	No effect or worsening
ACTH/cortisol effects	Not reported	Variable
Duration of effect after stopping	Anxiolytic effect lasted 1 week post-treatment	Rapid return of symptoms; withdrawal risk
Regulatory approval	Russia/Ukraine only (2009)	Widely approved internationally

Limitations of the Current Evidence

The Selank clinical evidence has real strengths — multiple trials, active comparators, biological markers, EEG data, cognitive testing. But several significant limitations apply:

Small sample sizes. The largest trial included 70 patients. The EEG study had 20. These numbers can detect large effect sizes but are underpowered for subtler differences.

No placebo-controlled trials. The core GAD trial compared Selank to medazepam, not placebo. Anxiety disorders have high placebo response rates (typically 30–40% in clinical trials), making it impossible to rule out placebo effects without a placebo arm.

Open-label designs. Patients and clinicians knew which treatment they were receiving, introducing expectation bias.

Single-country data. All clinical trials were conducted in Russia. No independent replication has been performed by Western research groups or regulatory agencies.

Limited follow-up. Treatment periods were typically 14 days, with post-treatment monitoring limited to 1 week. Long-term efficacy and safety remain unknown.

Publication access. Many original Russian-language papers are available only in translated abstracts, making full methodological review difficult for international researchers.

These limitations do not invalidate the findings, but they do mean the evidence falls short of what Western regulatory agencies would require for drug approval. For a broader look at peptides studied for mood and stress, see our guides on the best peptides for anxiety and stress and cognitive enhancement.

FAQ

Is Selank FDA-approved?

No. Selank is approved only in Russia and Ukraine (since 2009) for the treatment of generalized anxiety disorder. It has not undergone FDA review and is not approved for any indication in the United States.

How does Selank compare to benzodiazepines?

In Russian clinical trials, Selank showed comparable anxiolytic efficacy to medazepam and phenazepam on standardized rating scales. The key differences were what Selank did not produce: no sedation, no cognitive impairment, no dependence, no withdrawal symptoms. It also showed antiasthenic (anti-fatigue) and mild nootropic effects not seen with benzodiazepines.

What is the standard clinical dose?

In published trials, the standard dose was 2,700 mcg/day intranasally (900 mcg three times daily), administered for 14 days.

Does Selank affect the immune system?

Yes. Selank modulates cytokine expression (particularly IL-6), shifts the Th1/Th2 balance, and has demonstrated antiviral activity against influenza A, influenza B, herpes simplex, and other viruses in preclinical studies. These immunomodulatory properties come from its structural relationship to tuftsin, an endogenous immune-regulating peptide.

How does Selank relate to Semax?

Selank and Semax were both developed at the same Russian research institute and share the same Pro-Gly-Pro stabilizing tail. However, they come from different parent peptides — Selank from tuftsin (immune-related) and Semax from ACTH(4-10) (neuroendocrine). Selank is primarily anxiolytic with nootropic properties; Semax is primarily nootropic with neuroprotective properties. A functional connectivity study in 52 healthy participants showed distinct brain activation patterns for each peptide.

Are there side effects?

Reported side effects in clinical studies have been minimal: occasional headache, mild sinus irritation from nasal administration, sore throat, and nausea. No serious adverse events, tolerance, dependence, or withdrawal have been reported.

Why hasn't Selank been studied internationally?

Patent and commercial considerations, along with the regulatory and financial barriers of conducting international clinical trials, have limited its study to Russian institutions. There may also be less commercial incentive, since Selank cannot be patent-protected in the same way novel small molecules can.

The Bottom Line

Selank is one of the more scientifically interesting anxiolytic peptides to come out of Russian pharmacological research. The clinical trial data — while limited by small samples, open-label designs, and the absence of placebo controls — consistently shows anxiolytic efficacy comparable to benzodiazepines without the sedation, cognitive impairment, or dependence that make those drugs problematic for long-term use.

The preclinical mechanistic work is genuinely compelling. A peptide that modulates GABAergic gene expression, increases serotonin metabolism, upregulates BDNF, stabilizes endogenous enkephalins, and modulates immune cytokines hits several biologically plausible targets for anxiety and stress-related conditions. These are not vague claims — they are supported by specific gene expression studies, receptor binding assays, and neurochemical measurements.

What is missing is Western-standard validation. No placebo-controlled trial. No multicenter international study. No FDA or EMA review. No long-term safety data beyond a few weeks. These are not trivial gaps. They represent exactly the kind of evidence that separates a promising research compound from a proven therapeutic.

For patients and clinicians evaluating Selank, the honest assessment is this: the Russian clinical data suggests real anxiolytic activity with a favorable side-effect profile, but international replication is needed before confident clinical conclusions can be drawn.

References

1. Selank. Wikipedia. Wikipedia

2. Zozulya AA, Kost NV, Sokolov OY, et al. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(4):38-48. PubMed

3. Medvedev VE, et al. Rapid and slow response during treatment of generalized anxiety disorder with peptide anxiolytic selank. European Psychiatry. 2012;27(Suppl 1):P-1114. ScienceDirect

4. Medvedev VE, et al. Optimization of the treatment of anxiety disorders with selank. Zh Nevrol Psikhiatr Im S S Korsakova. 2015;115(6):33-40. PubMed; Medvedev VE, et al. A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(7):17-22. PubMed

5. Andreeva LA, et al. Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Front Pharmacol. 2017;8:89. PMC

6. Semenova TP, et al. Influence of Selank on serotonin metabolism and BDNF expression. Cited in multiple reviews. ResearchGate

7. Ershov FI, et al. Antiviral activity of immunomodulator Selank in experimental influenza infection. Vopr Virusol. 2009;54(5):19-24. PubMed

8. Uchakina ON, et al. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(5):71-75. PubMed