Is this the best nootropic peptide stack?

The Semax + Selank + Dihexa combination is one of the most comprehensive peptide-based nootropic stacks because it targets three distinct mechanisms: neurotrophic support (BDNF/NGF via Semax), emotional regulation (GABA via Selank), and synaptogenesis (HGF/c-Met via Dihexa). Whether it is the 'best' depends on individual needs. For pure focus, Semax alone may suffice. For anxiety-related cognitive impairment, Selank alone may be most relevant. The three-compound stack is for those seeking broad-spectrum cognitive enhancement across multiple domains.

Can I use Semax and Selank together in the same nostril?

It is generally recommended to administer them sequentially rather than simultaneously in the same nostril, waiting 5–10 minutes between applications to allow each to absorb properly. Some users alternate nostrils (Semax in the left, Selank in the right) for convenience. Using them at the same time is unlikely to cause adverse effects, but sequential administration ensures optimal absorption of each peptide.

Does Dihexa require injection?

No, Dihexa is orally active—a notable advantage over most peptides, which are degraded by gastrointestinal enzymes. Dihexa was specifically designed as a modified peptide that resists enzymatic degradation. It can be taken orally (capsule or dissolved) or sublingually (held under the tongue for 60–90 seconds). Some users prefer sublingual for faster absorption and higher bioavailability. No injection is required for any compound in this cognitive stack.

Is Selank addictive like benzodiazepines?

No. Unlike benzodiazepines (which bind directly to GABA-A receptors and produce tolerance, dependence, and withdrawal), Selank modulates GABAergic activity indirectly through allosteric mechanisms and enkephalin stabilization. No dependence, tolerance, or withdrawal symptoms have been reported in the clinical or research literature. This is one of Selank’s key advantages over traditional anxiolytic medications. However, as with any compound, use responsibly and cycle as recommended.

How does this stack compare to racetams or other synthetic nootropics?

Peptide nootropics (Semax, Selank, Dihexa) work through neurotrophic and neuromodulatory mechanisms—they promote brain health and plasticity rather than simply boosting neurotransmitter levels. Racetams (piracetam, aniracetam) primarily modulate AMPA and acetylcholine receptors. The mechanisms are complementary, and some researchers combine peptide and racetam nootropics. Peptide nootropics generally have stronger evidence for neuroprotection and long-term brain health, while racetams may provide more immediate cognitive stimulation.

Can I use this stack long-term for brain health?

Semax and Selank have been used as prescription medications in Russia for extended periods, suggesting reasonable long-term tolerability. Cycling (2–4 weeks on, 1–2 weeks off) is recommended to maintain receptor sensitivity and prevent adaptation. Dihexa has less long-term safety data—conservative cycling (4–8 weeks on, 2–4 weeks off) is prudent. For ongoing brain health support, many users cycle these peptides throughout the year, maintaining baseline supplementation with more conventional nootropics (omega-3s, lion’s mane) during off periods.

Will this stack help with age-related cognitive decline?

The mechanisms targeted by this stack—BDNF upregulation (Semax), stress reduction (Selank), and synaptogenesis (Dihexa)—are directly relevant to age-related cognitive decline. BDNF levels decrease with age, stress accumulates, and synaptic density diminishes. Dihexa in particular was studied for its ability to restore cognitive function in models of age-related memory impairment, showing promising results. However, human clinical trials specifically for age-related decline are lacking. This stack should complement (not replace) lifestyle factors known to support cognitive aging: exercise, sleep, social engagement, and nutrition.

The Cognitive Stack: Semax + Selank + Dihexa

Last updated: 2026-02-20

The Semax, Selank, and Dihexa cognitive enhancement stack combines three neuropeptides that target different aspects of brain function: neurotrophic factor production, anxiolysis and emotional regulation, and synaptogenesis. This multi-pathway approach addresses cognitive performance from multiple angles—focus, memory formation, neuroprotection, and stress resilience—rather than relying on a single mechanism.

Semax is a synthetic heptapeptide analog of ACTH(4–10) developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It upregulates brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), supporting neuronal health and plasticity.^[1] Selank is a synthetic heptapeptide analog of tuftsin with anxiolytic and nootropic properties, acting primarily through GABAergic modulation and enkephalin stabilization.^[2] Dihexa is a potent hexapeptide that activates the hepatocyte growth factor (HGF)/c-Met receptor system to promote synaptogenesis—the formation of new synaptic connections.^[3]

This guide details the evidence behind each compound, the synergy rationale, a complete dosing protocol, expected timeline, and safety information. All information is for educational purposes only. Consult a qualified healthcare professional before beginning any peptide protocol.

Compounds in This Stack

Semax

BDNF/NGF upregulation, neuroprotection, cognitive enhancement

Full Guide →

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic analog of the adrenocorticotropic hormone fragment ACTH(4–10), developed in Russia and approved there as a prescription nootropic and neuroprotective agent. It has been prescribed in Russia since 2011 for conditions including stroke, cognitive disorders, and optic nerve disease.^[1]

Mechanism in this stack: Semax serves as the primary neurotrophic agent. It upregulates BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor)—two key proteins that support neuronal survival, growth, differentiation, and synaptic plasticity. BDNF is often called "fertilizer for the brain" because it promotes the growth and maintenance of neural circuits involved in learning and memory. Semax also modulates dopaminergic and serotonergic neurotransmission, contributing to improved focus, motivation, and mood.

Parameter	Detail
Research Dosage	200–600 mcg per day (intranasal)
Administration	Intranasal spray (1–2 drops per nostril)
Frequency	2–3 times daily
Onset	Effects noticeable within minutes to hours (intranasal)
Regulatory Status	Approved prescription drug in Russia; research compound elsewhere

Selank

Anxiolytic, GABAergic modulation, emotional regulation, nootropic

Full Guide →

Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic heptapeptide analog of the immunomodulatory peptide tuftsin, developed at the same Russian institute as Semax. It is approved in Russia as a prescription anxiolytic and nootropic agent. Selank modulates GABAergic neurotransmission and stabilizes enkephalins (endogenous opioid peptides), producing anxiolytic effects without the sedation, cognitive impairment, or dependence associated with benzodiazepines.^[2]

Mechanism in this stack: Selank serves as the anxiolytic and emotional regulation component. Anxiety and stress are among the most significant cognitive performance degraders—elevated cortisol and sympathetic activation impair working memory, executive function, and learning. By modulating GABA-A receptor activity and stabilizing enkephalin concentrations, Selank reduces anxiety and improves stress resilience, creating a calm yet focused mental state optimal for cognitive performance. It also has independent nootropic effects, including enhanced memory consolidation.

Parameter	Detail
Research Dosage	250–500 mcg per day (intranasal)
Administration	Intranasal spray (1–2 drops per nostril)
Frequency	2–3 times daily
Onset	Anxiolytic effects within 15–30 minutes (intranasal)
Dependence Risk	No dependence or withdrawal reported (unlike benzodiazepines)

Dihexa

Synaptogenesis, HGF/c-Met activation, memory and learning enhancement

Full Guide →

Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a synthetic hexapeptide derived from angiotensin IV that was identified by Dr. Joseph Harding and colleagues at Washington State University. In preclinical studies, Dihexa demonstrated extraordinary potency—it was approximately 10 million times more potent than BDNF at promoting synaptogenesis, making it one of the most potent pro-cognitive compounds ever characterized.^[3]

Mechanism in this stack: Dihexa activates the hepatocyte growth factor (HGF)/c-Met receptor system in the brain. HGF/c-Met signaling promotes synaptogenesis (formation of new synaptic connections), dendritic spine growth, and neuronal survival. This mechanism is distinct from the BDNF/NGF pathway activated by Semax and the GABA pathway modulated by Selank, making Dihexa a true complement to the other two compounds. In animal models, Dihexa restored cognitive function in rats with scopolamine-induced memory impairment and enhanced learning in aged animals.

Parameter	Detail
Research Dosage	10–20 mg per day (oral/sublingual)
Administration	Oral, sublingual, or topical (crosses blood-brain barrier)
Frequency	Once daily
Oral Bioavailability	Orally active (modified peptide resists degradation)
Key Research	McCoy et al. 2013: 10 million times more potent than BDNF

How They Work Together

The Semax, Selank, and Dihexa cognitive stack creates a comprehensive nootropic environment by targeting three distinct and complementary aspects of brain function: neurotrophic support, emotional regulation, and synaptic connectivity.

Three Pathways to Cognitive Enhancement

Semax → Neurotrophic support (BDNF/NGF): Upregulates the growth factors that maintain neuronal health, promote plasticity, and support learning and memory. Also modulates dopamine and serotonin for improved focus and mood.^[1]
Selank → Anxiolysis and emotional regulation (GABA/enkephalins): Reduces anxiety and stress that impair cognitive performance, creating an optimal emotional state for focus and memory formation.^[2]
Dihexa → Synaptogenesis (HGF/c-Met): Promotes the formation of new synaptic connections, enhancing the brain’s structural capacity for learning, memory storage, and information processing.^[3]

The BDNF + HGF Synergy

Semax and Dihexa activate two different but complementary neurotrophic pathways. Semax upregulates BDNF, which strengthens existing synapses and supports long-term potentiation (LTP)—the cellular mechanism of memory formation. Dihexa activates HGF/c-Met signaling, which promotes the growth of new dendritic spines and synaptic connections. Together, they both strengthen existing neural circuits (Semax) and build new ones (Dihexa), creating a more robust and interconnected neural network.

Stress Removal + Growth Signal

Selank’s anxiolytic effects serve a critical synergistic function. Chronic stress and elevated cortisol actively suppress BDNF production and inhibit synaptogenesis. By reducing anxiety and modulating the stress response, Selank removes a biological barrier that would otherwise limit the effectiveness of Semax and Dihexa. In essence, Selank creates the neurochemical environment in which Semax and Dihexa can exert their maximum effects.

Non-Overlapping Administration Routes

A practical advantage of this stack is that Semax and Selank are administered intranasally (providing rapid brain access through the olfactory pathway), while Dihexa is taken orally or sublingually. This eliminates any injection requirement and makes the protocol highly convenient for daily use. The nasal route also bypasses the blood-brain barrier for Semax and Selank, enabling lower effective doses.

Researching peptides? We did the hard part.

Get our free Peptide Starter Kit — the 5 most researched compounds, simplified into one actionable guide.

Protocol & Dosage Schedule

Dosage Schedule

Compound	Dosage	Route	Timing
Semax	200–300 mcg per dose (2–3x/day)	Intranasal spray	Morning + early afternoon (+ optional midday)
Selank	250–500 mcg per dose (2–3x/day)	Intranasal spray	Morning + early afternoon (+ optional as needed)
Dihexa	10–20 mg per day	Oral or sublingual	Morning, with or without food

Cycle Length

Semax and Selank are typically cycled in 2–4 week blocks with 1–2 week breaks, though some protocols extend to 8 weeks continuous use. In Russia, prescribed Semax courses are typically 10–14 days. Dihexa cycling data is limited due to its relatively recent discovery, but 4–8 week cycles with 2–4 week breaks are a common approach. A conservative protocol runs all three for 4 weeks on / 2 weeks off.

Timing & Administration

Semax timing: Administer intranasally 1–2 drops per nostril, 2–3 times daily. The first dose should be in the morning, with subsequent doses spaced 4–6 hours apart. Avoid dosing in the evening as Semax’s dopaminergic effects may interfere with sleep. Clear nostrils before administration for optimal absorption.

Selank timing: Administer intranasally 1–2 drops per nostril, 2–3 times daily, at the same times as Semax. Selank and Semax can be administered sequentially (wait 5–10 minutes between each) or at the same time in separate nostrils if using separate spray bottles. Selank can also be used as-needed for acute anxiety or stress situations.

Dihexa timing: Take orally or sublingually once daily in the morning. Sublingual administration (held under the tongue for 60–90 seconds) may provide faster absorption and higher bioavailability than swallowing. Can be taken with or without food.

Sample daily schedule:

7:00 AM – Dihexa 10–20 mg (oral/sublingual)
7:15 AM – Semax 200–300 mcg intranasal + Selank 250–500 mcg intranasal
12:00 PM – Semax 200–300 mcg intranasal + Selank 250–500 mcg intranasal (optional midday dose)
4:00 PM – Selank 250 mcg intranasal (optional, as needed for afternoon stress/anxiety)
No evening dosing of Semax (avoid sleep disruption)

What to Expect

Cognitive enhancement from this stack includes both acute effects (noticeable within days) and cumulative neuroplastic effects (building over weeks). Semax and Selank produce rapid subjective improvements, while Dihexa’s synaptogenic effects build more gradually as new synaptic connections form.

Timeframe	Expected Observations
Days 1–3	Improved mental clarity and focus from Semax. Reduced anxiety and improved stress tolerance from Selank. Subtle increase in motivation and verbal fluency. Enhanced color perception and sensory acuity (commonly reported with Semax).
Week 1–2	Sustained improvement in focus duration and working memory. Noticeably improved mood stability and reduced reactivity to stress. Better reading comprehension and information retention. Enhanced creative thinking and problem-solving. Dihexa’s synaptogenic effects beginning.
Weeks 3–4	Cumulative neuroplastic improvements becoming apparent. Improved long-term memory formation and recall. Enhanced learning speed for new skills and information. Improved social cognition and verbal communication. Greater cognitive endurance during demanding mental tasks.
Weeks 5–8	Peak cognitive enhancement effects. Robust improvements in memory, focus, and executive function. Enhanced stress resilience and emotional regulation. Improved productivity and cognitive throughput. Assessment point for cycle continuation or break.

Safety & Contraindications

Known Side Effects

Semax reported side effects:

Mild nasal irritation or dryness (intranasal route)
Mild headache (usually resolves within the first few days)
Increased irritability at higher doses (reduce dose if this occurs)
Insomnia if dosed too late in the day
Generally well-tolerated; approved as a prescription drug in Russia with extensive safety data^[1]

Selank reported side effects:

Mild nasal irritation (intranasal route)
Drowsiness at higher doses (reduce dose or use earlier in the day)
Mild fatigue (uncommon)
No dependence, tolerance, or withdrawal symptoms reported (a significant advantage over benzodiazepines)^[2]

Dihexa reported side effects:

Limited human safety data (primarily preclinical research)
Theoretical concern: HGF/c-Met pathway is involved in cell proliferation and has been implicated in some cancers—though the doses used for cognitive enhancement are far below those associated with oncogenic signaling in the literature
Headache and gastrointestinal discomfort reported anecdotally
Long-term effects in humans are unknown^[3]

Contraindications and Cautions

Cancer history: Dihexa activates HGF/c-Met, a pathway that can promote cell proliferation. While cognitive-enhancement doses are very low, individuals with active cancer or a history of c-Met-driven tumors should avoid Dihexa.
Psychiatric conditions: Semax modulates dopamine, which may be problematic for individuals with bipolar disorder, schizophrenia, or other dopamine-sensitive conditions. Selank modulates GABA, which may interact with psychiatric medications. Consult a psychiatrist before combining with psychotropic medications.
Blood pressure: Semax is derived from ACTH, which can theoretically affect adrenal function. Monitor blood pressure, especially at higher doses.
Pregnancy and breastfeeding: No safety data for any of these compounds during pregnancy or lactation. Avoid use entirely.
Seizure disorders: Modulation of GABAergic systems (Selank) requires caution in individuals with epilepsy or seizure history.

Important Drug Interactions

Selank may potentiate the effects of benzodiazepines, alcohol, and other CNS depressants
Semax may interact with stimulants (caffeine, amphetamines) due to dopaminergic effects
Dihexa has no well-characterized drug interactions due to limited clinical data

Important: Semax and Selank are approved prescription drugs in Russia but are classified as research compounds in most other countries. Dihexa is a research compound with very limited human data. This information is for educational purposes only. Always consult a qualified healthcare professional before beginning any peptide protocol.

Frequently Asked Questions

References

Dolotov OV, Karpenko EA, Inozemtseva LS, et al.. Semax, an analogue of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research, 2006.
Zozulya AA, Gabaeva MV, Sokolov OY, Surkina ID, Kost NV. Personality, coping style, and constitutional neuroimmunology. Journal of Immunotoxicology, 2008.
McCoy AT, Benoist CC, Wright JW, et al.. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. Journal of Pharmacology and Experimental Therapeutics, 2013.
Levitskaya NG, Sebentsova EA, Andreeva LA, et al.. The neuroprotective effects of Semax in conditions modeling clinical applications. Doklady Biological Sciences, 2004.

Researching peptides? We did the hard part.

Get our free Peptide Starter Kit — the 5 most researched compounds, simplified into one actionable guide.

Individual Compound Guides

Semax Selank Dihexa

Peptides Insider Editorial Team

Our content is reviewed for accuracy and grounded in peer-reviewed research where available. We do not provide medical advice. Always consult a qualified healthcare professional.