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Apex Research Reference
SEMAX
ACTH(4-7)PGP — Neuroprotective Cognitive Enhancer & BDNF Upregulator
NOOTROPIC NEUROPROTECTION COGNITIVE BDNF STROKE APPROVED (RUSSIA)
01 / IDENTITY

Compound Profile

7
AMINO ACIDS
~0.86
kDa MW
NASAL
ROUTE (DESIGNED)
~2–4h
HALF-LIFE
SEQUENCE
Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP)
CLASSIFICATION
ACTH(4-7) fragment with C-terminal Pro-Gly-Pro extension. ACTH(4-7) = Met-Glu-His-Phe = the portion of adrenocorticotropic hormone responsible for its CNS effects, without the cortisol-stimulating activity. Semax has ZERO effect on cortisol or adrenal function.
MECHANISM
Multiple CNS targets: stimulates BDNF, NGF (nerve growth factor), and NT-3 (neurotrophin-3) expression. Enhances dopamine and serotonin turnover. Activates melanocortin receptors (MC4R) in the CNS. Potent neuroprotective via anti-apoptotic signaling. Improves cerebral blood flow via NO-dependent mechanisms.
DEVELOPER
Institute of Molecular Genetics, Russian Academy of Sciences. N.F. Myasoedov and colleagues, 1980s. Sister compound to Selank — both are Russian neuropeptide drugs with similar development history.
REGULATORY STATUS
Approved drug in Russia for stroke recovery, cognitive impairment, peptic ulcer, and optic nerve disease. Available as prescription nasal spray in Russia since 1990s. Research compound in Western markets.
VIAL SIZE
10mg lyophilized powder
02 / RESEARCH HISTORY

Development Timeline

1960s–1970s
Hans Selye and colleagues establish that ACTH has CNS effects independent of its adrenal (cortisol-stimulating) function. The short ACTH(4–10) fragment maintains cognitive effects of the full hormone. Research direction: isolate the cognitive-enhancing fragment and develop it as a standalone CNS drug.
1982–1990
N.F. Myasoedov at IMGR synthesizes Semax — ACTH(4-7) with Pro-Gly-Pro extension. The extension stabilizes the molecule (prevents rapid degradation) and enhances CNS penetration. Crucially: Semax has NO adrenocorticotropic activity — zero cortisol stimulation, zero adrenal effects. Animal studies show dramatic cognitive enhancement, neuroprotection, and enhanced learning.
1991–2002
Human clinical trials in Russia. Indications: stroke rehabilitation, ischemic brain disease, optic nerve atrophy, attention deficit states. Semax dramatically accelerates neurological recovery post-stroke — reduces cognitive deficit by 50%+ in ischemic stroke patients when administered within 24 hours. Approved as prescription drug in Russia.
2007–2014
BDNF upregulation mechanism confirmed — Semax increases BDNF expression by 1.5–2× in hippocampus and prefrontal cortex. This discovery elevates Semax's importance from a symptom-treating drug to a true neuroplasticity-promoting agent. Also shown to increase NGF and NT-3. Validated by multiple independent research groups.
2015–present
International biohacking community adopts Semax as premier cognitive enhancement tool. Intranasal formulation dominates user preference — faster onset, convenient, high bioavailability via olfactory pathway. Semax + Selank combination becomes the standard Russian nootropic protocol exported globally.
03 / BENEFITS

Primary Effects

01
Cognitive Enhancement — Focus, Processing Speed, Memory
Semax produces some of the most consistent and pronounced cognitive enhancement of any nootropic peptide. Users report dramatic improvements in focus, processing speed, and working memory within 20–30 minutes of intranasal administration. Unlike stimulants, there is no crash, jitteriness, or cardiovascular side effects. The enhancement feels "clean" — more like natural optimal performance than pharmacological stimulation.
02
BDNF & Neurotrophin Upregulation
Semax increases BDNF by 1.5–2× and also upregulates NGF and NT-3 — the complete neurotrophin triad. Together these drive: formation of new synaptic connections, neuronal survival and growth, myelin maintenance, and long-term memory consolidation. This is the molecular foundation for Semax's neuroprotective and learning-enhancement properties.
03
Neuroprotection — Stroke & Brain Injury Recovery
Clinically proven in Russia for ischemic stroke rehabilitation. Semax administered within 24 hours of stroke dramatically reduces infarct expansion and accelerates neurological recovery. Mechanism: anti-apoptotic signaling, improved cerebral blood flow, BDNF-driven neuroplasticity that helps the brain remap around damaged areas. Also studied for traumatic brain injury and optic nerve damage.
04
Dopaminergic Enhancement — Motivation & Drive
Semax stimulates dopamine turnover in the prefrontal cortex and striatum. This produces improved motivation, goal-directed behavior, and reward processing — without the addiction risk of direct dopamine agonists (because Semax works on synthesis/release, not receptor agonism). Relevant for ADHD-like symptoms, low motivation, and anhedonia.
05
Mood Elevation & Stress Resilience
Serotonin turnover enhancement + BDNF upregulation + dopamine optimization creates a comprehensive antidepressant-like effect. Semax elevates mood without euphoria or blunting — users report greater emotional resilience and reduced reactivity to stressors. Complements Selank's direct anxiolytic action in the standard combination protocol.
06
Optic Nerve & Visual System Protection
Unique indication: Semax is approved in Russia for optic nerve atrophy and glaucoma-related visual decline. BDNF is critical for retinal ganglion cell survival (the cells that form the optic nerve). Semax's neurotrophin upregulation protects these cells from degeneration. Eye drop formulation used in Russian ophthalmology.
04 / RECONSTITUTION

Preparation Protocol — Nasal Spray

⟶ DESIGNED ROUTE: INTRANASAL
Semax was developed by the Russian Academy of Sciences as a nasal spray — that's the route every Russian clinical trial used, and the route the FDA-equivalent approval covers in Russia. Intranasal delivery crosses the blood-brain barrier directly through the olfactory nerve, giving 5–15 min onset. Injection is possible but objectively worse for a brain-targeted peptide.
// 10MG VIAL — NASAL SPRAY RECONSTITUTION
10,000 mcg ÷ 6 mL BAC water = 1,667 mcg/mL = 167 mcg per spray
Add 6 mL bacteriostatic water → transfer to a sterile 10mL nasal spray bottle (0.1 mL per pump).
DOSE LEVEL SPRAYS TOTAL MCG NOTE
LOW1 spray 1 pump 167 mcg Sensitive users · intro dose
STANDARD2 sprays 1 per nostril 334 mcg Daily cognitive enhancement — the Russian clinical standard
HIGH4 sprays 2 per nostril 668 mcg Intensive cognitive work · Semax 0.1% equivalent
Priming the pump: Before first use, prime by spraying 3–4 pumps into a tissue (not your nose) to clear air from the dip tube. First time: nothing → nothing → fine mist. Only sprays that come out as a fine mist count toward your dose. Alternate nostrils day-to-day to reduce local irritation.
Injection option (rare): Some users reconstitute for subcutaneous injection using 3mL BAC water (33.3 mcg/unit). Subcutaneous works but is objectively slower-onset for brain effects than intranasal. Only useful if nasal irritation is a problem.
🧊
RECONSTITUTED SHELF LIFE
21 days after mixing
Short nootropic peptide. 21-day cap.
Storage: 2–8°C (fridge) · Protected from light · Do NOT freeze
Preload syringes/cartridges to minimize vial disturbance
Storage: Lyophilized — refrigerate (36–46°F / 2–8°C). Reconstituted: refrigerate, use within 30 days. If using intranasal spray: refrigerate the spray bottle between uses. Semax is moderately stable once reconstituted.
05 / DOSING PROTOCOL

Administration Guide

PROTOCOL DOSE TIMING DURATION CONTEXT
COGNITIVE 2 sprays · 334 mcg Morning fasted 5 days on / 2 off Daily focus, processing speed, productivity
LEARNING 3–4 sprays · 500–668 mcg AM before study session 4–8 weeks Accelerated learning, skill acquisition
RECOVERY 2 sprays · 334 mcg 2×/day 4–8 weeks Post-concussion, neurological recovery, burnout
STACK AM 2 sprays · 334 mcg AM (with Selank PM) Ongoing Full-day cognitive/mood optimization
Timing is important: Semax has a stimulating quality — avoid evening dosing if sleep is a priority. Morning or early afternoon is ideal. Some users experience mild insomnia if taken after 3 PM.
06 / TIMING

Administration Timing

PREFERRED WINDOW
Morning fasted — onset within 5–15 min (IN) or 20–30 min (SC). Cognitive effects peak at 30–60 min and persist 4–6 hours. Stack with morning coffee for synergistic alertness (different mechanisms).
INTRANASAL ONSET
5–15 minutes via olfactory pathway. Faster and often more subjectively potent than SC for cognitive effects. This is the preferred route for most users.
CYCLING
5 days on / 2 days off (weekdays on, weekends off) is the most common protocol. Prevents receptor downregulation. 4–8 week cycles with 1–2 weeks off also effective. The off-period BDNF effects persist weeks after cessation.
SEMAX + SELANK SYNERGY
Semax (AM, stimulating, dopaminergic) + Selank (PM, anxiolytic, serotonergic/GABAergic) = 24-hour cognitive optimization stack. The two peptides complement rather than compete — different receptor profiles and timing.
07 / BIOMARKERS

Monitoring Panel

// NEUROLOGICAL FUNCTION
MARKERTESTCLINICAL RANGEOPTIMAL ON SEMAX
BDNF (Serum)Neuroplasticity Marker Specialty lab (LabCorp) CLIN8–32 ng/mL OPT20+ ng/mL — Semax produces 1.5–2× upregulation above baseline
NGF (Nerve Growth Factor)Neurotrophin Specialty lab (serum or CSF) CLIN0.5–20 pg/mL (serum) OPTElevated above baseline (Semax increases NGF expression)
Cognitive BatteryProcessing Speed & Working Memory CNS Vital Signs or Cambridge Brain Sciences CLINAge-normalized percentile OPT>75th percentile; improving trend on cycle
// ADRENAL / HPA SAFETY (CONFIRM NO CORTISOL EFFECT)
MARKERTESTCLINICAL RANGEEXPECTED ON SEMAX
AM CortisolHPA Axis AM serum (8 AM) CLIN6–23 mcg/dL NOTENO CHANGE expected — Semax has zero adrenocorticotropic activity
ACTHAdrenocorticotropic Hormone Plasma ACTH CLIN7–63 pg/mL (AM) NOTENO CHANGE — confirms Semax acts on ACTH cognitive fragment, not pituitary ACTH pathway
// SUBJECTIVE TRACKING
MARKERMETHODBASELINETARGET
PHQ-9 Depression ScreenValidated Scale Self-report questionnaire BASEPre-cycle score OPTReduction in score over 2–4 weeks; 0–4 = minimal
Daily Energy RatingSelf-Report Scale 1–10 self-rating (morning) BASEPre-cycle average OPT>7/10 consistently; notable improvement within 3–7 days
08 / CYCLE PROTOCOL

Recommended Cycle

4–8
WEEKS ACTIVE
5 on/2 off
WEEKLY SCHEDULE
1–2
WEEKS OFF
AM
DOSE TIME
Standard Cycle: 2 sprays (334 mcg) intranasal, AM fasted, Monday–Friday. Run 4–6 weeks, then 1–2 weeks off. Within 3–7 days of starting, most users notice significantly improved focus and cognitive clarity. By week 2–3, BDNF-driven neuroplasticity benefits accumulate (better learning retention, mood improvement).
Intensive Protocol (Learning/High-Demand Period): 4 sprays (~668 mcg) intranasal AM during 4–6 week intensive study/work period. Higher dose amplifies BDNF response and cognitive enhancement. Take 1–2 weeks off after intensive cycle to allow neurotrophin levels to normalize.
Complete Russian Nootropic Stack: AM: Semax 2 sprays (334 mcg) intranasal — activating, focusing, dopaminergic
PM: Selank 2 sprays (334 mcg) intranasal — calming, anxiolytic, serotonergic
Both: BDNF upregulation from complementary mechanisms
Result: clear-headed focus during the day, calm and restorative evenings, progressive neuroplasticity building over weeks.
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Research Compound Notice: Semax is an approved prescription drug in Russia with 30+ years of clinical use and extensive safety data from Russian clinical trials. It has not been approved by the FDA. The compound has an excellent safety profile — no serious adverse effects documented across decades of Russian clinical practice. No reported dependence, withdrawal, or cognitive impairment. Mild temporary headache and nasal irritation (intranasal) are the most commonly reported side effects. Avoid evening dosing to prevent sleep disruption. Consult a healthcare provider.
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