Semax vs Selank: Head-to-Head Comparison

Semax and Selank work through fundamentally different neurotransmitter systems, producing complementary rather than overlapping cognitive effects.

Semax: ACTH-Derived Cognitive Enhancer

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a heptapeptide consisting of the ACTH(4–7) fragment extended with a C-terminal Pro-Gly-Pro (PGP) tripeptide that enhances metabolic stability. Despite its ACTH origin, semax does not affect cortisol or adrenal function.^[1]

• BDNF upregulation: Semax rapidly increases brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus, a mechanism central to learning, memory consolidation, and neuroplasticity.^[1]
• Monoaminergic activation: Semax activates both dopaminergic and serotonergic brain systems, increasing 5-HIAA levels in the striatum by up to 180% within 1–4 hours. This contributes to its focus-enhancing and mood-elevating effects.^[2]
• Neuroprotection: Semax promotes neuronal survival during hypoxia and glutamate toxicity, and modulates expression of genes related to immune and vascular function following cerebral ischemia.
• No hormonal effects: Despite being derived from ACTH, semax does not stimulate adrenal cortisol or aldosterone production.

Selank: Tuftsin-Derived Anxiolytic Nootropic

Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic analog of tuftsin, a tetrapeptide fragment of immunoglobulin G, extended with the same PGP stability tripeptide used in semax.^[3]

• GABAergic modulation: Selank modulates GABA-A receptor activity through allosteric mechanisms, producing anxiolytic effects comparable to benzodiazepines without the sedation, dependence, or cognitive impairment associated with that drug class.^[3]
• BDNF regulation: Like semax, selank increases BDNF levels in the hippocampus and prefrontal cortex, supporting cognitive function alongside its anxiolytic primary effect.^[4]
• Enkephalin metabolism: Selank inhibits the enzymatic breakdown of enkephalins (endogenous opioid peptides), which may contribute to its mood-stabilizing and stress-reducing effects.
• Immune modulation: As a tuftsin analog, selank retains immunomodulatory properties, influencing cytokine expression and immune cell activity.

The fundamental distinction is that semax is a stimulating nootropic that enhances dopaminergic drive, focus, and executive function, while selank is a calming nootropic that reduces anxiety and stabilizes mood while providing secondary cognitive support.

Both peptides have been studied extensively in Russia and have regulatory approval for clinical use, though their evidence bases differ in Western-standard clinical trial rigor.

Semax Research

• Stroke therapy: Semax is approved in Russia as an adjunctive treatment for acute ischemic stroke. Clinical studies report improved neurological outcomes when semax is administered intranasally during the acute stroke phase.
• BDNF studies: In vivo research demonstrated that semax application increases both protein and mRNA levels of BDNF and TrkB, and NGF mRNA levels in the hippocampus, with effects detectable within hours of administration.^[1]
• Cognitive enhancement: Studies in both animals and humans report that semax stimulates learning and memory formation, with effects on attention, information processing, and executive function.^[2]
• Genomic studies: Genome-wide transcriptional analysis revealed that semax affects expression of hundreds of genes related to immune function, vascular regulation, and neuroprotection in ischemic brain tissue.

Selank Research

• Anxiety disorders: Clinical studies demonstrated that selank has anxiolytic efficacy comparable to benzodiazepines in treating generalized anxiety disorder (GAD) and neurasthenia, without sedation or dependence.^[3]
• GABAergic effects: Research confirmed that selank modulates GABA-A receptor binding, with changes in specific binding sites detectable after intranasal administration.^[5]
• Memory protection: Selank protected against ethanol-induced memory impairment in rats by regulating BDNF content in hippocampus and prefrontal cortex.^[4]
• Morphine withdrawal: Research demonstrated selank attenuates aversive signs of morphine withdrawal, suggesting potential applications in addiction medicine.

Evidence limitations: Most clinical trials for both peptides were conducted in Russia and may not meet the same methodological standards as Western Phase III trials. Peer-reviewed publications are primarily in Russian-language journals, with selected studies translated or published in English.

Both semax and selank are administered intranasally, which provides direct access to the central nervous system through the olfactory mucosa.

Semax Dosing

• Standard dose: 200–600 mcg intranasally, 2–3 times daily.
• Concentration: Available as 0.1% (standard) and 1% (high-concentration) nasal drops in Russia.
• Onset: Effects typically noticed within 15–30 minutes of intranasal administration.
• Duration: Acute cognitive effects last approximately 4–6 hours per dose.
• Cycle length: Research protocols commonly run 10–14 days, with breaks between cycles. Russian clinical protocols specify 3–5-day treatment courses for acute stroke.

Selank Dosing

• Standard dose: 250–500 mcg intranasally, 2–3 times daily.
• Concentration: Available as 0.15% nasal drops in Russia.
• Onset: Anxiolytic effects may require several days of consistent use to reach full efficacy, though some acute effects are noticeable within hours.
• Duration: Anxiolytic effects persist longer than semax’s cognitive effects and may build cumulatively over a treatment course.
• Cycle length: Russian clinical protocols recommend 14-day treatment courses, with the option to repeat after a break.

Both peptides have favorable safety profiles based on clinical use in Russia and preclinical research.

Semax Safety

• Clinical track record: Used clinically in Russia since the 1990s with a well-established safety profile for short-term use.
• Reported effects: Mild nasal irritation at the application site. Rare reports of headache and irritability, typically at higher doses.
• No hormonal effects: Despite its ACTH-derivative origin, semax does not produce cortisol elevation or adrenal stimulation.
• Stimulatory profile: Some users report difficulty sleeping if semax is taken too late in the day, consistent with its dopaminergic activation.

Selank Safety

• Clinical track record: Approved in Russia for anxiety disorders, with clinical use demonstrating good tolerability.^[3]
• Compared to benzodiazepines: Selank produces anxiolytic effects without the sedation, cognitive impairment, or dependence potential of benzodiazepines.
• Reported effects: Mild nasal irritation. Occasional reports of drowsiness at higher doses, consistent with its GABAergic mechanism.
• Immune modulation: Selank’s immunomodulatory properties are generally considered beneficial but may require consideration in individuals with autoimmune conditions.

The choice between semax and selank depends primarily on whether the research goal is cognitive stimulation or anxiety reduction.

Choose Semax For:

• Focus and attention enhancement: Semax’s dopaminergic activation makes it better suited for tasks requiring sustained focus, concentration, and executive function.
• Memory and learning research: The rapid BDNF upregulation supports research on memory formation and neuroplasticity.
• Neuroprotection studies: Semax’s stroke therapy approval and neuroprotective mechanisms make it the choice for ischemia and neurodegeneration research.
• Productivity-focused protocols: The stimulating profile is better suited for demanding cognitive tasks.

Choose Selank For:

• Anxiety reduction: Selank’s primary application is anxiolytic, making it the clear choice when anxiety reduction is the primary goal.
• Stress-related cognitive impairment: When cognitive performance is hampered by anxiety or stress, selank’s calming effects may improve cognition indirectly.
• Benzodiazepine alternative research: Selank’s comparable anxiolytic efficacy without sedation or dependence makes it a compelling research alternative.
• Immune modulation: Selank’s tuftsin-derived immunomodulatory properties add value for research involving immune function.

Combining Both

Some researchers use semax and selank together, leveraging semax’s cognitive stimulation with selank’s anxiolytic effects for a balanced nootropic profile. The two peptides work through different receptor systems, making pharmacological interaction unlikely. The combination may be particularly relevant when both cognitive enhancement and anxiety management are desired.