Selank vs. Semax: Nootropic Peptide Comparison

Two peptides. Both developed in Russia. Both delivered through the nose. Both acting on the brain. Yet Selank and Semax occupy very different pharmacological territory — and choosing between them (or combining them) requires understanding what each one actually does at the molecular level.

Selank is built for calm. Semax is built for cognition. That one-line summary captures the broad strokes, but the real story involves tuftsin fragments, ACTH analogs, GABA receptors, neurotrophic factors, and a body of clinical data that — while mostly Russian — is more substantial than most people realize.

This guide breaks down the science, the clinical evidence, and the practical differences so you can have an informed conversation with your healthcare provider about which peptide (if either) makes sense for your situation.

Quick Comparison Table
Origins: Two Branches of Soviet Peptide Science
How Selank Works
How Semax Works
Clinical Evidence: Selank
Clinical Evidence: Semax
Pharmacokinetics and Dosing
Side Effects and Safety
Stacking Selank and Semax
Regulatory Status
The Bottom Line
References

Quick Comparison Table

Parameter	Selank	Semax
Amino Acid Sequence	Thr-Lys-Pro-Arg-Pro-Gly-Pro	Met-Glu-His-Phe-Pro-Gly-Pro
Parent Molecule	Tuftsin (immune peptide from IgG)	ACTH(4-10) (pituitary hormone fragment)
Primary Classification	Anxiolytic	Nootropic / Neuroprotectant
Key Mechanism	GABA modulation, enkephalin stabilization	BDNF/NGF upregulation, dopaminergic signaling
Primary Effect	Anxiety reduction without sedation	Cognitive boost, memory, neuroprotection
Secondary Effects	Mild nootropic, immunomodulatory	Mild anxiolytic, anti-inflammatory
Intranasal Bioavailability	~92.8%	High (exact figure unpublished)
Plasma Half-Life	~7-10 minutes (rat data)	~20-30 minutes
Duration of Effects	Several hours	2-4 hours
Russian Approval	Yes (anxiolytic, 2009)	Yes (nootropic / neuroprotectant)
FDA Status	Not approved	Not approved
Dependence Risk	None documented	Very low
Common Side Effects	Mild nasal irritation	Nasal irritation, possible mild stimulation

For deeper profiles of each peptide, see our full guides on Selank and Semax.

Origins: Two Branches of Soviet Peptide Science

Both Selank and Semax came out of the same institution — the Institute of Molecular Genetics at the Russian Academy of Sciences — during a decades-long program to develop peptide-based neurological drugs. But they started from completely different biological templates.

Selank: The Immune Peptide That Calms the Brain

Selank is a synthetic analog of tuftsin, a tetrapeptide (Thr-Lys-Pro-Arg) first identified in the 1970s at Tufts University in Massachusetts. Tuftsin is a natural component of immunoglobulin G and plays a role in immune cell activation. Russian researchers recognized that tuftsin fragments had effects beyond immunity — they influenced mood and anxiety.

The problem was stability. Native tuftsin breaks down in seconds in the bloodstream. So researchers appended a Pro-Gly-Pro tripeptide to the C-terminus, creating the heptapeptide we now call Selank. That three-amino-acid tail was the same stabilizing strategy they had already used for Semax. The result: a molecule that survives long enough to cross the blood-brain barrier and reach its targets.

Semax: The Hormone Fragment That Sharpens Thought

Semax takes its starting material from a completely different source — adrenocorticotropic hormone (ACTH), the pituitary hormone that triggers cortisol release. Specifically, Semax is built on the ACTH(4-10) fragment: Met-Glu-His-Phe. This fragment retains the neurotropic properties of ACTH (effects on learning, memory, and attention) while being stripped of all hormonal activity. It does not raise cortisol. It does not affect the adrenal glands.

Like Selank, Semax carries the Pro-Gly-Pro stabilizer on its C-terminus to resist enzymatic degradation. The final sequence — Met-Glu-His-Phe-Pro-Gly-Pro — entered Russian clinical use as a treatment for stroke, optic nerve disease, and cognitive impairment.

Both peptides share that PGP tail. Both are heptapeptides. But their core sequences, their receptor targets, and their downstream effects diverge sharply.

How Selank Works

Selank operates through at least four interconnected mechanisms. No single pathway fully explains its effects — the anxiolytic and nootropic properties likely emerge from their combined activity. For a full analysis of the clinical data, see our Selank clinical research review.

GABAergic Modulation

GABA is the brain's primary inhibitory neurotransmitter, and virtually every effective anti-anxiety drug in modern medicine works on the GABA system. Benzodiazepines (Xanax, Valium, Klonopin) amplify GABA signaling through allosteric modulation of GABA-A receptors. Selank appears to work through a similar mechanism.

Research published in Frontiers in Pharmacology demonstrated that Selank affects the expression of multiple genes involved in GABAergic neurotransmission, including genes encoding GABA-A receptor subunits. The anxiolytic effect resembles that of benzodiazepines — but without the sedation, motor impairment, tolerance, or withdrawal that make benzodiazepines so problematic for long-term use.

Why the difference? One likely factor: Selank also modulates wakefulness-related gene expression (specifically the hypocretin/orexin system), which may counterbalance the sedative tendency of amplified GABA signaling.

Enkephalin Stabilization

Enkephalins are endogenous opioid peptides that modulate mood, pain perception, and stress response. They are rapidly degraded by enzymes called enkephalinases. Selank inhibits these enzymes, effectively raising brain levels of leu-enkephalin.

Clinical data from the GAD trial (discussed below) found that patients with generalized anxiety disorder had abnormally low leu-enkephalin half-lives, and that Selank treatment normalized these levels — a change that correlated with symptom improvement.

Serotonin and Dopamine Effects

Selank modulates both serotonergic and dopaminergic receptors. Of particular interest: it activates expression of the Drd5 gene, which encodes the dopamine D5 receptor — a receptor involved in long-term potentiation, the cellular mechanism underlying memory formation. This may explain why Selank produces mild cognitive benefits alongside its primary anxiolytic effect.

BDNF Regulation

Animal studies show that Selank prevents ethanol-induced BDNF dysregulation in the hippocampus and prefrontal cortex. At a dose of 0.3 mg/kg over 7 days in rats, Selank blocked memory impairment and normalized BDNF content in brain structures critical for cognition. This neuroprotective dimension gives Selank a dual identity: anxiolytic first, but with meaningful cognitive-protective properties.

How Semax Works

Where Selank operates primarily through receptor modulation and enzyme inhibition, Semax works largely by driving the production of growth factors that neurons need to survive, connect, and function. For a detailed look at the neuroprotective data, see our Semax neuroprotective research review.

BDNF and NGF Upregulation

This is the headline mechanism. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are proteins that support neuronal survival, growth, and synaptic plasticity. Low BDNF is associated with depression, cognitive decline, and neurodegeneration. Raising BDNF is one of the most studied strategies for improving brain function.

Semax does this aggressively. The data is striking:

In vitro (glial cells): A single application of Semax increased BDNF mRNA levels 8-fold and NGF mRNA levels 5-fold within 30 minutes.
In vivo (rat hippocampus): A single intranasal dose (50 mcg/kg) produced a 1.4-fold increase in BDNF protein, a 3-fold increase in BDNF mRNA, and a 2-fold increase in TrkB mRNA (the BDNF receptor).
In stroke models: Semax upregulated BDNF, NGF, neurotrophin-3, and their high-affinity receptors (TrkA, TrkB, TrkC) in ischemic brain tissue.

These are not subtle changes. An 8-fold increase in BDNF mRNA from a single peptide application is among the most potent neurotrophic responses documented in the literature.

Dopaminergic and Serotonergic Activation

Semax activates both dopamine and serotonin systems in the brain. This dual-system activation explains the combination of improved focus (dopamine) and mood stabilization (serotonin) that users and researchers describe. It also provides a plausible mechanism for Semax's reported benefits in attention-deficit conditions — ADHD involves disruption of both dopamine and BDNF pathways, and Semax targets both.

Melanocortin System Interaction

As an ACTH analog, Semax likely interacts with melanocortin receptors (MC3R and MC4R), though the exact binding profile remains under investigation. The melanocortin system influences learning, memory consolidation, and motivation. This interaction may explain why Semax effects extend beyond simple neurotransmitter modulation into territory that includes behavioral drive and motivational states.

Anti-Inflammatory and Vascular Effects

Genome-wide transcriptional analysis following cerebral ischemia identified 394 genes affected by Semax treatment. Many of these were involved in immune response and vascular function. Semax suppressed inflammatory mediators (IL-1b, IL-6, TNF-alpha) while enhancing immune cell mobilization and blood vessel formation. This anti-inflammatory profile contributes to neuroprotection, particularly in stroke contexts.

Clinical Evidence: Selank

Generalized Anxiety Disorder Trial (Zozulia et al., 2008)

The most cited Selank study enrolled 62 patients with generalized anxiety disorder (GAD) and neurasthenia. Thirty patients received Selank; 32 received medazepam (a benzodiazepine). Assessment used the Hamilton Anxiety Scale, Zung Self-Rating Anxiety Scale, and Clinical Global Impression scale.

Results: Selank matched medazepam's anxiolytic effect. But Selank also delivered anti-asthenic (energy-boosting) and psychostimulant effects that the benzodiazepine did not. Patients treated with Selank showed normalized leu-enkephalin metabolism, and the degree of normalization correlated with anxiety improvement.

Comparison with Phenazepam (Medvedev et al., 2014)

A second trial compared Selank against phenazepam (a potent benzodiazepine widely used in Russia) in 60 patients with anxiety and somatoform disorders. Selank demonstrated pronounced anxiolytic effects plus a mild nootropic benefit. Notably, the anxiolytic effect persisted for a full week after the last dose — suggesting that Selank triggers lasting downstream changes rather than simply occupying receptors during the dosing window.

The Benzodiazepine Advantage

Across studies, Selank's safety profile stands out most clearly when compared to the drug class it's designed to replace. No sedation. No motor impairment. No tolerance development after 14 days. No withdrawal syndrome upon discontinuation. No documented dependence.

This profile makes Selank theoretically interesting for the millions of patients who need anxiety treatment but cannot tolerate benzodiazepine side effects — though international trials are still needed to validate these Russian findings.

For the complete clinical picture, see our Selank clinical research analysis.

Clinical Evidence: Semax

Ischemic Stroke Trials

Semax has been most thoroughly studied in stroke patients. In one trial, 30 patients in the acute phase of hemispheric ischemic stroke received Semax added to standard therapy, compared to 80 control patients receiving standard therapy alone. EEG monitoring, somatosensory evoked potentials, and clinical rating scales tracked outcomes.

Results: Adding Semax to standard stroke care accelerated the recovery of damaged neurological functions. Motor disorder regression was particularly notable — patients regained movement faster than controls.

A larger study of 110 post-stroke patients (mean age 58) examined Semax during rehabilitation. Patients receiving Semax (6,000 mcg/day for 10 days, two courses with a 20-day interval) showed elevated plasma BDNF levels that remained high throughout the study period — consistent with the preclinical data showing robust neurotrophic factor upregulation.

Cognitive Performance in Healthy Subjects

A human study in healthy individuals tested Semax at doses of 250-1,000 mcg/kg. Subjects showed improved attention and short-term memory. EEG changes were consistent with the patterns seen with other established neuroprotective drugs. The most clinically relevant finding: effects on work efficiency lasted 20-24 hours after a single intranasal administration.

Optic Nerve Disease

Semax is also prescribed in Russia for optic nerve pathologies, at higher doses (600-900 mcg daily). The neurotrophic mechanism — specifically NGF upregulation — is thought to support optic nerve cell survival.

For a comprehensive review, see our Semax neuroprotective research overview.

Pharmacokinetics and Dosing

Understanding how these peptides move through the body helps explain why they are dosed the way they are.

Selank

Intranasal bioavailability: 92.8% — exceptionally high for a peptide
Onset: Detectable in plasma within 30 seconds of intranasal administration
Plasma half-life: Approximately 7-10 minutes (rat data); the native peptide is rapidly cleaved into the active metabolite Thr-Lys-Pro-Arg
Duration of effect: Several hours despite the short half-life, likely due to downstream gene expression changes and receptor-mediated signaling cascades
Typical clinical doses: 600-900 mcg/day intranasally, divided into 2-3 administrations
Cycle length in Russian clinical practice: 10-21 days

Semax

Intranasal bioavailability: High (exact percentage not published, but clinical efficacy via this route is well-established)
Onset: Effects noticeable within 15-30 minutes
Plasma half-life: Approximately 20-30 minutes
Duration of effect: 2-4 hours for standard Semax; 6-12 hours for the N-Acetyl Semax Amidate variant
Typical clinical doses: 200-900 mcg/day intranasally for cognitive support; up to 6,000 mcg/day for stroke (under medical supervision)
Cycle length in Russian clinical practice: 5-14 days for cognitive use; up to 16 days for neurological conditions

Modified Variants

Both peptides have modified variants. N-Acetyl Selank Amidate adds acetyl and amide groups to protect against enzymatic degradation, extending the half-life to 4-6 hours with 30-50% higher bioavailability. N-Acetyl Semax Amidate uses the same strategy, yielding a longer half-life and extended duration of effects.

These modified forms are not the versions studied in Russian clinical trials, which used standard Selank and Semax.

Side Effects and Safety

Selank Safety Profile

Selank's side effect profile is remarkably clean across published research:

Most common: Mild nasal irritation or unusual taste/odor immediately after administration
Sedation: Not observed (a key differentiator from benzodiazepines)
Dependence: None documented in clinical studies or decades of Russian clinical use
Tolerance: No tolerance development observed after 14 days of continuous use
Withdrawal: No withdrawal syndrome reported upon discontinuation
Cognitive impairment: None — Selank appears to mildly improve cognitive function rather than impair it
Motor coordination: Unaffected

Semax Safety Profile

Semax is generally well-tolerated but carries a slightly broader side effect spectrum, consistent with its more stimulatory profile:

Most common: Nasal irritation from intranasal delivery
Mild stimulation: Some users report feeling "wired" or overstimulated, particularly at higher doses
Blood pressure: Temporary increases possible, especially at higher doses
Sleep disruption: Possible if dosed too late in the day (similar to caffeine timing considerations)
Irritability: Reported by some users, potentially related to dopaminergic effects, sometimes occurring as the dose wears off
Blood glucose: Theoretical concern for diabetic patients, though clinical significance is uncertain
Dependence: Very low risk; no withdrawal syndrome documented

Head-to-Head Safety

Selank has the edge on tolerability. Its anxiolytic mechanism produces calming effects without stimulation, making it harder to "feel bad" on Selank. Semax, with its dopaminergic and stimulatory profile, requires more attention to timing and individual sensitivity. Most reported side effects with Semax are dose-related and manageable.

Neither peptide has undergone the kind of large-scale, long-term safety monitoring that FDA-approved drugs receive. The existing safety data comes predominantly from Russian clinical settings and should be interpreted with that limitation in mind.

Stacking Selank and Semax

Using both peptides together has become a common practice in the nootropic community, and the pharmacological rationale is straightforward: Semax provides cognitive acceleration while Selank prevents the anxiety or overstimulation that can accompany it.

The Logic

Semax drives dopamine and BDNF. These are performance-enhancing changes — better focus, faster processing, stronger memory encoding. But dopaminergic stimulation can also produce restlessness, irritability, or anxiety in sensitive individuals. Selank's GABA modulation and enkephalin stabilization counterbalance these effects, smoothing out the cognitive boost into what users describe as "calm focus."

Common Approaches

Separated dosing: Semax in the morning for cognitive work; Selank in the afternoon or during stress peaks. Spacing by 4-6 hours helps distinguish each peptide's contribution.
Simultaneous dosing: Once individual responses are established, some users administer both peptides at the same time without issues.
Cycling: Both peptides are typically cycled (10-30 days on, 1-3 weeks off) to maintain sensitivity and prevent receptor adaptation.

Caution

Stacking research-grade peptides without medical supervision adds complexity and risk. Individual responses vary. The combination has not been studied in controlled clinical trials. Anyone considering this approach should discuss it with a physician who understands peptide pharmacology.

For broader context on nootropic peptide combinations, see our guide on the best nootropic peptides and the Dihexa vs. Semax vs. Selank comparison.

Regulatory Status

Neither Selank nor Semax is approved by the U.S. Food and Drug Administration. They are not classified as prescription medications or dietary supplements in the United States.

In Russia and certain CIS countries, both are registered pharmaceuticals:

Selank is approved for generalized anxiety disorder and neurasthenia (since 2009)
Semax is included on the Russian List of Vital and Essential Drugs (since 2011), approved for stroke, cognitive impairment, and optic nerve disease

This regulatory split matters. The Russian approval reflects genuine clinical data and institutional review, but the approval process differs from FDA standards in trial design, sample sizes, and transparency. International validation — multicenter, double-blind, placebo-controlled trials meeting Western regulatory standards — has not been completed for either peptide.

In the U.S., both peptides exist in a gray area. They have been available through compounding pharmacies and research chemical suppliers. The FDA's 2023 crackdown on peptide compounding has narrowed access, though the regulatory picture continues to evolve.

The Bottom Line

Selank and Semax are not competitors — they are complementary tools that address different neurological priorities.

Choose Selank if anxiety, stress reactivity, or emotional dysregulation is the primary concern. Its benzodiazepine-like anxiolytic effect without sedation, dependence, or cognitive impairment makes it pharmacologically unique. It also carries BDNF-protective and mild nootropic properties as secondary benefits. See our guide on the best peptides for anxiety and stress for context on where Selank fits among other options.

Choose Semax if cognitive performance, memory, neuroprotection, or recovery from neurological injury is the priority. Its ability to upregulate BDNF and NGF — sometimes dramatically — sets it apart from most nootropic compounds. The stroke data is the strongest clinical evidence for either peptide. For other cognitive-focused options, see our guide on peptides for memory and age-related cognitive decline.

Consider both if the goal is sharper cognition under stressful conditions — the combination offers a pharmacological logic that individual dosing does not.

Talk to a doctor regardless. These are potent neuroactive compounds, not supplements. The evidence base, while real, is geographically concentrated in Russian research institutions. Anyone considering either peptide should work with a healthcare provider who can evaluate individual risk factors, monitor responses, and adjust protocols based on clinical judgment rather than internet anecdotes.

For a broader overview of nootropic peptides including Cerebrolysin and others, see our complete guide to nootropic peptides.

References

Zozulia AA, et al. "Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia." Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2008;108(4):38-48. PMID: 18454096.
Medvedev VE, et al. "A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders." Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014;114(7):3-9. PMID: 25176261.
Kasian A, et al. "GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells." Frontiers in Pharmacology. 2017;8:89. doi: 10.3389/fphar.2017.00089.
Volkova A, et al. "Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission." Frontiers in Pharmacology. 2016;7:31. doi: 10.3389/fphar.2016.00031.
Inozemtseva LS, et al. "Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats." Bulletin of Experimental Biology and Medicine. 2019;167(5):641-644. PMID: 31625062.
Dolotov OV, et al. "Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus." Brain Research. 2006;1117(1):54-60. PMID: 16996037.
Shadrina MI, et al. "Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog." Neuroscience Letters. 2001;308(2):115-118. PMID: 11457573.
Shadrina MI, et al. "Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10." Neuroscience Letters. 2007;417(2):201-205.
Gusev EI, et al. "Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)." Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2001. PMID: 11517472.
Medvedeva EV, et al. "The efficacy of semax in the treatment of patients at different stages of ischemic stroke." Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2018. PMID: 29798983.
Dergunova LV, et al. "The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis." BMC Genomics. 2014;15:228. doi: 10.1186/1471-2164-15-228.
Dergunova LV, et al. "Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia." International Journal of Molecular Sciences. 2024;25(20):11198. doi: 10.3390/ijms252011198.
Kozlovskii II, Danchev ND. "The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats." Neuroscience and Behavioral Physiology. 2003;33(7):639-643.
Eremin KO, et al. "Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents." Neurochemical Research. 2005;30(12):1493-1500.
Vakhitova YV, et al. "Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats." Bulletin of Experimental Biology and Medicine. 2022;174(1):72-76. doi: 10.1007/s10517-022-05624-x.

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