MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Semax Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Semax is a synthetic heptapeptide analogue of adrenocorticotropic hormone fragment ACTH(4-10), with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. Designed at the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry by Kaplan, Ashmarin and colleagues, it strips away the steroidogenic portion of native ACTH and adds a Pro-Gly-Pro stabilising tail to extend metabolic half-life. Semax binds melanocortin MC4R/MC3R receptors and produces rapid hippocampal upregulation of BDNF and its TrkB receptor within thirty minutes of intranasal dosing, alongside modulation of dopaminergic, serotonergic, and cholinergic transmission across cortex and striatum (PMID: 16252214). Russian controlled trials in acute hemispheric ischemic stroke reported reduced lesion progression and faster neurological recovery at 12-18 mg/day intranasally (PMID: 21626054). Researchers study it for attention, working memory, post-stroke recovery, optic nerve disease, and resilience under hypoxic or fatigue stress.
Reconstitute: Add 3 mL bacteriostatic water → 1.67 mg/mL concentration.
Easy measuring: At 1.67 mg/mL, 1 unit = 0.01 mL = 0.0167 mg (17 mcg) on a U-100 insulin syringe.
Storage: Lyophilized frozen; reconstituted refrigerated; avoid repeated freeze–thaw.
Half-life: Plasma terminal half-life is approximately 20-30 minutes, but BDNF/TrkB gene expression effects persist many hours per dose, supporting one to three daily intranasal administrations.
Route: Intranasal as a 0.1% or 1% solution is the registered Russian route; subcutaneous is used in research but is less potent on a per-microgram basis than intranasal.
Status: Registered in Russia since 1994 and listed on the Russian Federation List of Vital and Essential Drugs for stroke, optic nerve disease, and cognitive disorders. Not FDA, EMA, or MHRA approved.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall; avoid foaming.
Gently swirl/roll until dissolved (do not shake).
Inject slowly; wait a few seconds before withdrawing the needle.
Do not aspirate for subcutaneous injections; inject slowly and steadily[7].
Interactive Semax Syringe Calculator
Currently visualizing the 5 mg vial reconstituted with 3 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 5mg dry powder in 3mL water yields 1.67 mg/mL. To evaluate a 250mcg dose, pull to 15.0 units (15 syringe ticks).
U-100 Syringe Representation
15.0 Units (15 Ticks)
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Week | Daily Dose (mcg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 200 mcg | 12 units (0.12 mL) |
| Weeks 3–4 | 300 mcg | 18 units (0.18 mL) |
| Weeks 5–6 | 400 mcg | 24 units (0.24 mL) |
| Weeks 7–12 | 500 mcg | 30 units (0.30 mL) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
| Concentration (mcg/mL) | Pump Output (mL/actuation) | Amount per Actuation (mcg) | Actuations per mL (1 ÷ pump output) | Total Actuations in Reconstituted Volume |
|---|---|---|---|---|
| 1,667 | 0.10 | 166.7 | 10.0 | 30.0 (3.0 mL × 10) |
| 1,667 | 0.13 | 216.7 | 7.7 | 23.1 (3.0 mL × 7.7) |
| 2,500 | 0.10 | 250.0 | 10.0 | 20.0 (2.0 mL × 10) |
| 2,500 | 0.13 | 325.0 | 7.7 | 15.4 (2.0 mL × 7.7) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 5 mg vial.
Peptide Vials (Semax, 5 mg each):
- check8 weeks ≈ 5 vials
- check12 weeks ≈ 8 vials
- check16 weeks ≈ 10 vials
Insulin Syringes (U‑100):
- checkPer week: 7 syringes (1/day)
- check8 weeks: 56 syringes
- check12 weeks: 84 syringes
- check16 weeks: 112 syringes
Bacteriostatic Water (10 mL bottles): Use ~3.0 mL per vial for reconstitution.
- check8 weeks (5 vials): 15 mL → 2 × 10 mL bottles
- check12 weeks (8 vials): 24 mL → 3 × 10 mL bottles
- check16 weeks (10 vials): 30 mL → 3 × 10 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check8 weeks: 112 swabs → recommend 2 × 100‑count boxes
- check12 weeks: 168 swabs → recommend 2 × 100‑count boxes
- check16 weeks: 224 swabs → recommend 3 × 100‑count boxes
Mechanism of Action (MOA)
Semax was designed by Ashmarin and Kaplan as a metabolically stable analogue of the ACTH(4-10) sequence, which had been known since the 1960s to possess CNS activity stripped of corticosteroid release. Adding Pro-Gly-Pro to the C-terminus extends in vivo half-life from minutes (native ACTH(4-10)) to hours, while preserving the pharmacophore that engages melanocortin receptors. Intranasal delivery is the dominant route in both clinical and research use because the peptide is absorbed across the olfactory and respiratory mucosa and reaches the central nervous system via olfactory and trigeminal nerve pathways, with cerebrospinal fluid concentrations measurable within minutes. Bioavailability is several-fold higher intranasally than by subcutaneous injection, and intranasal Semax is more potent in learning tasks than the same dose administered intraperitoneally. Pharmacologically, Semax binds with modest affinity at melanocortin receptors (MC4R/MC3R) and produces downstream activation of trophic, anti-inflammatory, and antioxidant pathways. Within 30 minutes of a single intranasal dose, Semax upregulates BDNF mRNA and protein in the hippocampus along with its TrkB receptor, providing a molecular substrate for cognitive enhancement [2]. Dolotov and colleagues showed that Semax dose-dependently increases secreted BDNF in cultured rat basal forebrain neurons. Beyond neurotrophin induction, Semax modulates the cholinergic, dopaminergic, and serotonergic systems: it elevates dopamine and serotonin metabolite ratios in striatum and frontal cortex and potentiates acetylcholine release in the hippocampus, mechanisms thought to underlie its attention- and memory-enhancing effects [1]. Semax also exerts neuroprotective actions independent of trophic signaling: it inhibits enkephalinase activity, prolonging endogenous opioid signaling; it suppresses pro-inflammatory cytokines IL-6 and TNF-alpha in ischemic tissue; and it shifts microglial polarization toward anti-inflammatory phenotypes. In stroke models, Semax limits infarct volume, reduces apoptosis in the penumbra, and accelerates functional recovery. Clinically, intranasal Semax at 600–1500 mcg in healthy volunteers improves attention, short-term memory, operator performance under fatigue, and resistance to hypoxic stress over 20–24 hours per dose [4]. Higher doses (3000–18000 mcg/day) are used in acute stroke and severe cognitive disorders, divided across 2–3 nasal administrations. The peptide does not cross the placenta in measurable quantities and does not produce HPA axis stimulation, having been deliberately separated from the steroidogenic portion of ACTH. Clearance is rapid (terminal half-life roughly 20–30 minutes), but gene-expression effects on BDNF/TrkB persist for many hours after a single dose, supporting clinical regimens of one to three daily intranasal administrations.
Clinical Trial Efficacy Highlights
- starIn a placebo-controlled trial conducted by the Gusev group, 30 patients with acute hemispheric ischemic stroke received intranasal Semax 12 mg/day (moderate stroke) or 18 mg/day (severe stroke) for 5–10 days alongside standard therapy. Treated patients showed faster recovery of neurological function and reduced lesion progression on CT compared to 80 matched controls receiving standard therapy alone [3].
- starKaplan and colleagues reported that intranasal Semax at 250–1000 mcg in healthy adult volunteers produced sustained improvement in attention, short-term memory, and operator work efficiency lasting 20–24 hours after a single dose, with maximal effect at approximately 16 mcg/kg [1].
- starDolotov, Eremin and colleagues demonstrated that Semax dose-dependently upregulates BDNF and TrkB mRNA in rat hippocampus within 30 minutes of intranasal dosing, with effects sustained for at least 4 hours — a direct molecular correlate of cognitive enhancement [2].
- starLevitskaya and Kamensky reviewed 15 years of Semax research showing nootropic activity across multiple animal models (active avoidance, water maze, passive avoidance) and clinical populations, with consistent improvements in learning, memory consolidation, and attention [4].
- starIn acute ischemic stroke patients, Semax produced measurable shifts in inflammatory mediators: upregulation of IL-10 and reductions in IL-8 and C-reactive protein, consistent with an anti-inflammatory neuroprotective mechanism beyond direct trophic effects.
- starPediatric and adult studies of Semax in attention deficit and minimal cerebral dysfunction reported improvements in concentration, behavioral measures, and EEG normalization at intranasal doses of 200–600 mcg/day over 30-day courses.
- starSemax has been studied in optic nerve atrophy and glaucomatous optic neuropathy with reports of improved visual acuity and visual field expansion at intranasal doses of 600–900 mcg/day for 10-day courses, supporting CNS-wide neuroprotective utility.
- starAnimal studies of chronic Semax administration showed no evidence of tolerance, dependence, or withdrawal, and the peptide does not stimulate the HPA axis despite its ACTH-derived parent structure, distinguishing it from corticotropin-like cognitive enhancers [1].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningSemax is well tolerated at clinical and research doses; the most frequent adverse effect is transient nasal irritation, sneezing, or rhinorrhea at the site of intranasal application, typically resolving within minutes.
- warningMild headache may occur, particularly at higher cumulative daily doses (above 1500 mcg) or with concurrent stimulant use; it usually responds to dose reduction or adequate hydration.
- warningIncreased alertness can produce difficulty initiating sleep if Semax is administered late in the day; dosing earlier in the morning and at midday is the conservative practice in research protocols.
- warningUnlike classical psychostimulants, Semax has not been associated with abuse liability, tolerance, dependence, or withdrawal in animal models or in Russian clinical experience spanning 30 years.
- warningRare reports describe transient blood pressure elevations at supraphysiologic doses; cardiovascular monitoring is reasonable in patients with uncontrolled hypertension, particularly when high stroke-protocol doses are used.
- warningSemax does not stimulate cortisol release despite its derivation from ACTH(4-10), but the small theoretical risk of melanocortin-mediated effects on appetite, sexual function, or skin pigmentation warrants monitoring in long-term users.
- warningSafety in pregnancy and lactation has not been established; use during pregnancy and breastfeeding is not recommended absent controlled human data.
- warningDrug interactions are poorly characterized; concurrent use with MAO inhibitors, dopaminergic agonists, or other CNS stimulants should be approached cautiously given Semax's monoaminergic effects.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Semax dosage?expand_more
Standard research dosing is 600–1500 mcg/day intranasally, divided across one to three administrations. Russian stroke protocols use 12,000–18,000 mcg/day for 5–10 days. Most cognitive enhancement use lies between 300–900 mcg administered in the morning and early afternoon.
How is Semax administered?expand_more
Semax is administered intranasally, typically as a 0.1% or 1% saline solution delivering 50–500 mcg per drop or spray. The intranasal route achieves higher CNS bioavailability than subcutaneous injection and is the route used in all Russian clinical protocols.
Can Semax be stacked?expand_more
Semax is frequently stacked with Selank for combined cognitive and anxiolytic effect, with the two peptides administered at least 10 minutes apart to avoid nasal absorption interference. Combination use is supported by anecdotal and small observational data rather than randomized trials.
What are the side effects of Semax?expand_more
Most users tolerate Semax well; transient nasal irritation and occasional headache are the most common complaints. Insomnia can occur if dosed late in the day. No tolerance, dependence, or withdrawal syndrome has been documented in 30 years of Russian clinical use.
Is Semax FDA approved?expand_more
No. Semax is a registered prescription drug in Russia (since 1994) on the Russian List of Vital and Essential Medicines for stroke and cognitive disorders, but it is not approved by the FDA, EMA, or MHRA. In the United States and European Union, Semax is sold only as a research chemical.
Academic References & Study Citations
Kaplan AY, Kochetova AG, Nezavibathko VN, Rjasina TV, Ashmarin IP. Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neurosci Res Commun. 1996;19(2):115-123. View Scientific Paper →
Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54-60. View Scientific Paper →
Gusev EI, Skvortsova VI, Miasoedov NF, et al. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. View Scientific Paper →
Levitskaya NG, Kamensky AA. The nootropic and analgesic effects of Semax given via different routes. Neurosci Behav Physiol. 2012;42(8):811-815. View Scientific Paper →
Ashmarin IP, Nezavibatko VN, Levitskaya NG, Koshelev VB, Kamensky AA. Design and study of peptide nootropic analog of ACTH(4-10): 15 years experience. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997;47(2):420-30. View Scientific Paper →
Shevchenko KV, Nagaev IY, Andreeva LA, et al. Kinetics of Semax penetration into the brain and blood of rats after intranasal administration. Bioorg Khim. 2006;32(1):64-70. View Scientific Paper →
Medvedeva EV, Dmitrieva VG, Povarova OV, et al. The peptide Semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia. Genes (Basel). 2017;8(3):109. View Scientific Paper →
Stavchansky VV, Tvorogova TV, Botsina AY, et al. The effect of Semax and its C-terminal fragment PGP on the expression of VEGF family genes and their receptors in experimental focal ischemia of the rat brain. J Mol Neurosci. 2011;45(2):177-85. View Scientific Paper →
Asmarin IP, Kaplan AY, Kuznetsova IL, et al. The nootropic adrenocorticotropin analogue 4-10 Semax (15 years experience in development and study). Zh Vyssh Nerv Deiat. 1997;47:419-425. View Scientific Paper →
Vyunova TV, Andreeva LA, Shevchenko KV, Myasoedov NF. Peptide-based anxiolytics: the molecular aspects of heptapeptide selank biological activity. Protein Pept Lett. 2018;25(10):914-923. View Scientific Paper →