Selank: Anxiolytic Peptide Research Profile
Selank is a synthetic anxiolytic peptide that modulates GABA, serotonin, and dopamine. Approved in Russia since 2009, it reduces anxiety without sedation or dependence.
Most anxiety medications come with a trade-off. Benzodiazepines work fast, but they fog your thinking, build tolerance, and create dependence. What if a peptide could calm anxiety through similar brain pathways — without those downsides? That question has driven more than two decades of research into Selank, a synthetic peptide developed in Russia that acts on GABA receptors, modulates serotonin and dopamine, and appears to protect neurons rather than impair them.
Selank is one of the few peptides to complete Phase III clinical trials for an anxiety indication, and it has been an approved pharmaceutical in Russia since 2009. Outside Russia, it remains unapproved and largely unstudied in Western clinical settings — a gap that makes the existing research both promising and incomplete.
Here is what the science actually shows.
Quick Facts
| Property | Detail |
|---|---|
| Full name | Selank (TP-7) |
| Type | Synthetic heptapeptide |
| Amino acid sequence | Thr-Lys-Pro-Arg-Pro-Gly-Pro |
| Derived from | Tuftsin (immunoglobulin G fragment) |
| Molecular weight | ~751 Da |
| Primary classification | Anxiolytic peptide |
| Secondary effects | Nootropic, immunomodulatory, antiviral |
| Administration | Intranasal spray (primary), subcutaneous injection |
| Developed by | Institute of Molecular Genetics, Russian Academy of Sciences |
| Regulatory status | Approved in Russia (2009); not FDA-approved |
What Is Selank?
Selank is a synthetic peptide made of seven amino acids: Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was built by taking the first four amino acids of tuftsin — a naturally occurring peptide found in the heavy chain of human immunoglobulin G (IgG) — and attaching three additional amino acids (Pro-Gly-Pro) to its tail end.
Tuftsin was discovered at Tufts University in the 1970s and is known for stimulating immune cell activity, particularly in macrophages and natural killer cells. On its own, tuftsin breaks down almost immediately in the bloodstream. The three extra amino acids in Selank make it far more resistant to enzymatic degradation, extending its action and allowing it to reach the brain after intranasal administration.
The result is a peptide that inherited tuftsin's immune-modulating properties but also developed pronounced effects on anxiety, cognition, and mood. Russian researchers classify Selank as an anxiolytic (anti-anxiety) agent with nootropic (cognition-boosting) and immunomodulatory properties.
Development History
Selank emerged from a collaboration between the Institute of Molecular Genetics of the Russian Academy of Sciences and the V.V. Zakusov Research Institute of Pharmacology in the early 1990s. Russian pharmacologists had noticed that short peptide fragments from larger proteins often had unexpected biological activity. Tuftsin — a four-amino-acid fragment already known to stimulate immune function — was a natural starting point. By modifying it for stability, the researchers discovered that the resulting molecule (initially called TP-7) had both immune and neurological effects.
Preclinical testing through the late 1990s and early 2000s mapped out Selank's core mechanisms. Clinical trials followed, culminating in Phase III studies in patients with generalized anxiety disorder (GAD). In 2009, the Russian Ministry of Health approved Selank as a 0.15% nasal spray solution.
Selank is now sold in Russian and Ukrainian pharmacies alongside Semax, another peptide from the same program. Semax (derived from the pituitary hormone ACTH) is classified as a nootropic, while Selank is classified primarily as an anxiolytic. Both share the Pro-Gly-Pro stabilizing tail and a development lineage with Epitalon, another Russian-developed peptide.
How Selank Works: Mechanisms of Action
Selank does not work through a single receptor or pathway. Research has identified at least four distinct mechanisms, which likely operate together.
GABA Receptor Modulation
The most well-studied mechanism involves the GABAergic system — the brain's primary inhibitory network and the same system targeted by benzodiazepines like diazepam (Valium) and alprazolam (Xanax).
A 2016 study in Frontiers in Pharmacology analyzed 84 genes involved in GABAergic neurotransmission in the rat frontal cortex after Selank administration. Significant changes appeared in 45 genes within one hour, with a gene expression pattern that positively correlated with GABA itself — suggesting Selank mimics or amplifies GABA signaling.
But Selank does not bind directly to the GABA binding site. Instead, it acts as a positive allosteric modulator — it binds elsewhere on the GABA-A receptor and increases its sensitivity to GABA. Benzodiazepines use a similar strategy but at a different binding site, and they force GABA-A receptors into a more active state so aggressively that the brain compensates by reducing sensitivity over time — producing tolerance and dependence. Selank's modulation appears gentler, which may explain why studies have not observed these effects.
The study also found that Selank downregulated GABA transporter genes (Slc32a1, Slc6a1, Slc6a11). Since these transporters pull GABA out of the synapse, reducing them allows GABA to remain active longer — a second way to boost inhibitory signaling.
Serotonin and Dopamine Effects
Selank's effects extend beyond the GABA system. Research by Narkevich et al. (2008) found that Selank altered levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) across multiple brain regions in mice, including the hippocampus, hypothalamus, striatum, and frontal cortex.
The gene expression data from Volkova et al. adds more detail. Selank upregulated dopamine receptor genes (Drd1a, Drd2, Drd3) and serotonin receptor genes (Htr3a, Htr1b) within one hour. At the three-hour mark, Selank — but not GABA — activated the Drd5 gene, which encodes a dopamine receptor involved in long-term potentiation and memory formation. This may partly explain Selank's nootropic effects, which GABA alone does not produce. Selank also increased dopamine metabolites (DOPAC and HVA) in the frontal cortex and hippocampus, pointing to faster dopamine turnover in regions linked to emotion and cognitive control.
BDNF and Neuroplasticity
Brain-derived neurotrophic factor (BDNF) supports neuron survival, promotes new synaptic connections, and plays a direct role in learning and memory. Low BDNF levels are consistently linked to depression and anxiety disorders.
Selank upregulates BDNF expression in the hippocampus and prefrontal cortex. In a 2019 study, rats exposed to chronic ethanol developed memory impairments and abnormal BDNF levels. Selank (0.3 mg/kg daily for 7 days) both prevented memory deficits and normalized BDNF content. This BDNF-boosting effect connects Selank to other compounds studied for neuroplasticity, including Semax.
Enkephalin Stabilization
Selank's most unusual mechanism involves the endogenous opioid system — specifically, enkephalins. These short peptides bind to delta- and mu-opioid receptors, producing mild pain relief, anxiety reduction, and mood elevation. They normally break down within seconds because multiple enzymes (aminopeptidase N, dipeptidyl peptidase IV) degrade them rapidly.
Selank inhibits these enkephalin-degrading enzymes, slowing the breakdown of endogenous enkephalins and extending their signaling time. This is not the same as directly activating opioid receptors the way morphine does — Selank does not bind to opioid receptors at all. Instead, it props up the body's own opioid peptides, allowing them to work longer.
Critically, researchers found that Selank's anxiety-reducing effects could be blocked by naloxone, an opioid receptor blocker. If Selank worked independently of the opioid system, naloxone would have no effect. This naloxone reversal strongly supports the role of enkephalin stabilization in Selank's mechanism.
Anxiety Research
The GAD Clinical Trial
The most cited study was published by Zozulia et al. (2008) and involved 62 patients with generalized anxiety disorder (GAD) and neurasthenia. Thirty patients received Selank intranasally; 32 received medazepam, a benzodiazepine. Patients were evaluated using the Hamilton Anxiety Rating Scale (HARS), the Zung Self-Rating Anxiety Scale, and the Clinical Global Impression (CGI) scale.
Selank's anxiolytic effects were comparable to medazepam across all three scales. But Selank also produced antiasthenic and psychostimulant effects — patients reported less fatigue and more mental energy — something medazepam did not do. Overall, 81% showed marked improvement and 19% showed mild improvement.
Rapid vs. Gradual Responders
A follow-up study presented at the European Psychiatric Association Congress examined 20 GAD patients receiving Selank at 2,700 mcg/day intranasally and identified two response groups:
- Rapid responders (40%): Abrupt symptom reduction within 1-3 days. By Day 3, average HARS score dropped from 20.3 to 7.0 (p < 0.01).
- Gradual responders (60%): Steady improvement over two weeks. HARS score fell from 16.1 to 6.2 by Day 14 (p < 0.01).
Both groups reached similar endpoints, but a 65% reduction in anxiety scores within three days — without sedation — is unusual for any anxiolytic compound.
Comparison to Benzodiazepines
Across multiple studies, Selank produces anxiolytic effects comparable to low-dose benzodiazepines — without the problematic side effects:
| Feature | Selank | Benzodiazepines |
|---|---|---|
| Anxiety reduction | Comparable | Comparable |
| Sedation | None reported | Common |
| Memory impairment | None; may improve memory | Common (anterograde amnesia) |
| Tolerance / dependence | Not observed | Common with chronic use |
| Withdrawal symptoms | Not observed | Can be severe |
| Cognitive effects | May improve cognition | Impairs cognition |
This comparison, drawn from Russian clinical data, is the central argument for Selank's potential. An anxiolytic as effective as benzodiazepines without dependence or cognitive impairment would be a significant advance — if the findings hold up in larger, internationally replicated trials.
Chronic Stress Models
In a 2017 study in Bulletin of Experimental Biology and Medicine, rats subjected to unpredictable chronic mild stress (UCMS) were treated with Selank, diazepam, or both. Selank alone was the most effective treatment for elevated anxiety. The combination outperformed either drug alone, suggesting Selank and diazepam work through complementary but non-overlapping pathways on the GABA-A receptor.
Cognitive and Nootropic Research
Selank's cognitive effects go beyond simply reducing anxiety (though less anxiety alone can improve thinking):
Learning: In a 2003 study, Selank "significantly activated the learning process in rats with initially poor learning ability" after just a single dose.
Memory protection: Kolik et al. (2019) showed that Selank prevented ethanol-induced memory impairment in rats, with treated animals performing significantly better on object recognition tasks.
Memory in healthy animals: Rats treated intranasally with Selank at 16 mcg/kg scored 71% correct answers on a memory test compared to 41% in controls — an effect lasting up to 24 hours.
Gene expression: Selank uniquely activated the Drd5 dopamine receptor gene (GABA did not), which is directly involved in long-term potentiation — the cellular process underlying memory formation.
The proposed mechanism involves Selank's combined action: BDNF supports new synaptic connections, dopamine modulation improves attention, serotonin stabilizes mood, and GABA modulation reduces neural "noise."
Immunomodulatory Properties
Because Selank is derived from tuftsin — a peptide whose primary role is immune activation — it retains immunomodulatory properties that make it unusual among anxiolytic compounds.
In mouse models, Selank changed the expression of 34 inflammation-related genes in the spleen, including genes for chemokines, cytokines, and their receptors. It modulates interleukin-6 (IL-6) expression and shifts the Th1/Th2 cytokine balance — the two main branches of the adaptive immune response. Selank also significantly altered Bcl6 expression, a gene central to immune cell differentiation.
The complement system is affected too: researchers observed a three-fold decrease in C3 mRNA within 30 minutes of Selank injection, along with changes in Casp1 (inflammatory signaling) and Il2rg (a component of several interleukin receptors).
These immune effects connect Selank to other immunomodulatory peptides like Thymosin Alpha-1 and LL-37, though the mechanisms differ. Where Thymosin Alpha-1 acts primarily on T-cell maturation and LL-37 functions as a direct antimicrobial, Selank works more broadly on inflammatory gene expression and cytokine balance.
Antiviral Research
One of the more surprising findings in Selank research involves antiviral activity. Studies from the Institute of Molecular Genetics demonstrated activity against influenza A (H3N2), influenza B, avian influenza (H5N1), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), cytomegalovirus (CMV), and murine encephalomyocarditis virus (EMCV).
In one in vitro study, Selank added to cell cultures 24 hours before influenza virus inoculation completely suppressed viral reproduction. In animal studies, the highest survival rates occurred when Selank was given preventively before infection.
The antiviral mechanism appears to involve selective interferon-alpha (IFN-alpha) induction without affecting levels of IL-4, IL-10, or TNF-alpha. Fragment analysis found that the tetrapeptide Arg-Pro-Gly-Pro (the last four amino acids of Selank) showed the strongest antiviral activity, with Gly-Pro identified as the minimum pharmacophore.
These findings are preliminary and come entirely from Russian research groups — they have not been replicated internationally or tested in human clinical trials for antiviral indications. But the dual neurological and antiviral properties of a single peptide are scientifically interesting.
How Selank Is Administered
Selank is primarily administered as a nasal spray. The nasal mucosa provides a direct route to the brain through olfactory and trigeminal nerve pathways, bypassing first-pass liver metabolism that would otherwise break down the peptide before it reached its target.
Russian clinical dosing: The approved formulation is a 0.15% solution — two drops (roughly 75 mcg per drop) per nostril, three times daily, for up to 14 days (approximately 900 mcg per day).
Research dosing: Clinical studies have used 250 mcg to 2,700 mcg daily. Subcutaneous injection is an alternative route, with lower doses (150 to 300 mcg/day) since injection avoids the losses associated with nasal delivery.
Onset and duration: Intranasal Selank is absorbed within minutes, with measurable effects in 30 to 90 minutes. The peptide itself clears circulation in about 10 minutes, but downstream effects on gene expression and neurotransmitter levels persist much longer — some studies report cognitive effects lasting up to 24 hours after a single dose.
Safety and Side Effects
Selank's safety profile is one of its most frequently cited advantages. Across available preclinical and clinical literature, reported side effects are rare and mild:
Commonly reported: Mild nasal irritation or sore throat (related to the administration route), occasional headache, and mild nausea (uncommon).
Not observed: Sedation, cognitive impairment, tolerance development, physical dependence, withdrawal symptoms, or motor impairment. Preclinical toxicology studies showed low toxicity even at doses well above typical research levels.
Important caveats: The FDA has noted potential concerns about immunogenicity — the possibility that the body could mount an immune response against the peptide. Because Selank is derived from a human immunoglobulin fragment, this risk may be lower than for fully synthetic peptides, but it has not been ruled out. Most safety data comes from Russian clinical trials, not the multi-year studies typical of FDA approval. Long-term safety beyond a few months has not been rigorously established.
Anyone considering Selank alongside other CNS-active medications (SSRIs, benzodiazepines, MAO inhibitors) should work with a qualified healthcare provider, as Selank's effects on serotonin, dopamine, and GABA create theoretical interaction potential.
Selank vs. Semax
Selank and Semax were developed by the same Russian institute, share the Pro-Gly-Pro stabilizing tail, and are both available as nasal sprays in Russian pharmacies. But they are different molecules with different targets.
| Feature | Selank | Semax |
|---|---|---|
| Derived from | Tuftsin (immune peptide from IgG) | ACTH 4-10 (pituitary hormone fragment) |
| Primary effect | Anxiolytic (anti-anxiety) | Nootropic (cognitive boost) |
| Main mechanisms | GABA modulation, enkephalin stabilization | BDNF upregulation, dopamine/serotonin modulation |
| Best described as | Calm alertness | Focused stimulation |
| Medical uses (Russia) | GAD, neurasthenia | Stroke recovery, cognitive impairment |
The simplest way to think about it: Semax is the accelerator — it pushes cognitive function forward. Selank is the stabilizer — it maintains cognitive function under stress by reducing anxiety. Some Russian clinicians use both together, and preclinical research suggests the combination may have complementary effects.
Regulatory and Legal Status
Russia and Ukraine: Approved pharmaceutical since 2009, available by prescription as a 0.15% nasal spray classified as an anxiolytic.
United States: Not FDA-approved for any indication. In October 2023, the FDA placed Selank on its Category 2 list, prohibiting compounding pharmacies from producing it. In September 2024, the FDA removed Selank acetate from this list after nominators withdrew their submissions. Even so, Selank remains in regulatory limbo — not an approved drug, not a recognized supplement, and its compounding status continues to shift. This situation mirrors other research peptides like BPC-157 and Thymosin Beta-4.
Europe and other regions: No marketing authorization from the EMA or equivalent bodies outside Russia and the CIS.
Limitations of the Evidence
For all of Selank's promising research, there are real limitations worth noting:
Geographic concentration. Nearly all Selank studies come from Russian institutions, many affiliated with the institutes that developed it. This does not mean the research is wrong, but independent replication by Western research groups — a cornerstone of scientific reliability — has not happened.
Small sample sizes. The key GAD trial included 62 patients; the rapid-responder study included 20. FDA approval for an anxiety drug would typically require hundreds or thousands of patients across multiple sites.
Limited long-term data. Clinical studies generally examined Selank over 14 days to a few weeks. Long-term efficacy and safety data are not available in published literature.
Animal model reliance. The most detailed mechanistic studies (gene expression, neurotransmitter effects, BDNF regulation) were conducted in rodents. Animal models do not always predict human responses accurately.
No Western clinical trials. No registered trials for Selank appear on ClinicalTrials.gov. A significant portion of the Russian-language literature has not been published in internationally indexed journals.
These limitations do not invalidate the existing research. They do mean that Selank should be viewed as a promising but incompletely validated compound — not a proven therapy with a settled evidence base.
Frequently Asked Questions
What is Selank used for?
In Russia, Selank is prescribed for generalized anxiety disorder and neurasthenia. Research has also explored cognitive improvement, immune modulation, and antiviral activity, though these uses are not formally approved anywhere.
How is Selank different from benzodiazepines?
Both affect the GABA-A receptor, but benzodiazepines strongly amplify GABA signaling (causing sedation, memory impairment, and dependence with chronic use). Selank acts as a gentler allosteric modulator without these side effects in studies conducted so far, and it also has nootropic effects that benzodiazepines lack.
Is Selank addictive?
No dependence or addiction has been observed in any published study — in animals or humans. This is consistent with its mechanism as a mild allosteric modulator rather than a direct GABA agonist.
How quickly does Selank work?
In the clinical rapid-responder study, 40% of patients experienced significant anxiety reduction within 1 to 3 days. Intranasal Selank is absorbed within minutes, with measurable effects appearing within 30 to 90 minutes.
Is Selank legal in the United States?
Selank is not FDA-approved. It was briefly placed on the FDA's Category 2 restricted list in 2023 but was removed in September 2024. Its legal status for compounding and research use continues to evolve.
What is the difference between Selank and Semax?
Selank (derived from tuftsin) is primarily an anxiolytic — it reduces anxiety and stabilizes mood. Semax (derived from ACTH) is primarily a nootropic — it boosts focus, memory, and cognitive drive. Some people use both together for complementary effects.
Does Selank affect the immune system?
Yes. Derived from tuftsin (an immune-activating peptide), Selank modulates dozens of inflammation-related genes, affects cytokine balance, and may have antiviral activity. These immune effects distinguish it from other anxiolytic compounds, including peptides like DSIP, which focus primarily on the nervous system.
The Bottom Line
Selank is one of the most thoroughly studied anxiolytic peptides in existence — at least within Russian pharmacology. Its multi-target mechanism (GABA modulation, serotonin/dopamine effects, BDNF upregulation, enkephalin stabilization) sets it apart from single-mechanism drugs, and its clean safety profile compared to benzodiazepines makes a compelling case on paper.
The clinical data tells a consistent story: Selank reduces anxiety as effectively as low-dose benzodiazepines, does not cause sedation or cognitive impairment, shows no signs of dependence, and may actually improve cognitive function. The added immune and antiviral properties — inherited from tuftsin — make it genuinely unusual in the anxiolytic space.
What Selank lacks is independent validation. No Western clinical trials, small patient populations, and limited long-term safety data all represent gaps that need filling before it can be considered a proven therapeutic option by international standards.
For now, Selank occupies a unique position: too well-studied to dismiss, not well-studied enough to fully endorse. It is a research compound worth watching — and one that shows how promising science can get stuck in regulatory and geographic silos while millions of people look for better anxiety treatments.
This article is for educational purposes only and does not constitute medical advice. Selank is not FDA-approved for any indication. Consult a qualified healthcare provider before considering any peptide therapy.
References
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