library.onepin.app/semax Peptide Education Library
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OnePin Peptide Library · Cognitive & Mood

Cognitive & Mood Synthetic heptapeptide Not FDA-approved · investigational

Semax

Semax Acetate

Synthetic heptapeptideACTH(4-10) analog with Pro-Gly-Pro extensionBDNF/TrkB pathway activatorNootropic / cognitive enhancer

Semax is a synthetic heptapeptide derived from ACTH(4-10), the biologically active fragment of adrenocorticotropic hormone, with a stabilizing Pro-Gly-Pro C-terminal extension that protects against enzymatic degradation. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, Semax has been approved in Russia and Ukraine as a prescription medication for cognitive enhancement, neuroprotection, and stroke recovery. It exerts nootropic effects primarily through upregulation of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling, without the adrenal-stimulating effects of full-length ACTH. Semax is stimulating and is best administered in the morning to avoid sleep disruption.

Quick Start
Route
Nasal spray or Subcutaneous (SubQ) injection
Start low
200-600 mcg daily
Frequency
Daily, morning only
Timing
No fasting required. Morning dosing due to stimulating effects. Avoid late-day or evening.

Intranasal: Any time of day. Cognitive effects peak 15-30 minutes after dosing. SubQ: Same timing. No fasting required. Multiple daily doses for sustained effect.

Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first
Quick Start
Conservative start
200-600 mcg daily · Nasal spray or Subcutaneous (SubQ) injection · Daily, morning only
Lowest starting point. Hold about a week to assess tolerance before stepping up.
200-600 mcg daily
Daily, morning only
Standard
Nootropic Stimulation
200-500 mcg · SubQ · Daily
human study · Asmarin et al. 1997 (Zh Vyssh Nerv Deiat Im I P Pavlova 47(2):420-30)
200-500 mcg
Daily
Reconstitution CalculatorU-100
050100u
Draw to
units
01

How it works

Semax activates melanocortin receptors (MC3R, MC4R) in the brain, triggering downstream signaling that upregulates BDNF expression and TrkB receptor activation in the hippocampus and cortex. BDNF is the primary neurotrophin supporting neuronal survival, differentiation, and synaptic plasticity (the cellular basis of learning and memory). Semax also modulates serotonergic and dopaminergic neurotransmission, increases expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF), and enhances cerebral blood flow. The Pro-Gly-Pro C-terminal modification protects against DPP-IV and aminopeptidase degradation, extending the effective half-life. Critically, Semax does NOT stimulate the adrenal cortex at standard doses (unlike full-length ACTH), meaning no cortisol elevation.

Semax activates melanocortin receptors (MC3R, MC4R) in the brain, triggering downstream signaling that upregulates BDNF expression and TrkB receptor activation in the hippocampus and cortex. BDNF is the primary neurotrophin supporting neuronal survival, differentiation, and synaptic plasticity (the cellular basis of learning and memory). Semax also modulates serotonergic and dopaminergic neurotransmission, increases expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF), and enhances cerebral blood flow. The Pro-Gly-Pro C-terminal modification protects against DPP-IV and aminopeptidase degradation, extending the effective half-life. Critically, Semax does NOT stimulate the adrenal cortex at standard doses (unlike full-length ACTH), meaning no cortisol elevation.

02

What to expect

Early
Days 1–7

Days 1-3: Many users report noticeable cognitive effects within the first few days. Improved focus, verbal fluency, and mental energy. Stimulating nature becomes apparent. If sleep is disrupted, dose is too late in the day.

Mid
Weeks 2–4

Weeks 1-4: Consistent cognitive enhancement. BDNF upregulation effects compound over time. Memory and learning capacity improve. Mood stabilization. Best effects typically reported at 2-4 weeks.

Later
Weeks 4–12

Weeks 4-8: Sustained neuroplasticity benefits. Some users report the effects plateau, which is one reason for cycling. The 4-8 week cycle allows receptor sensitivity to reset.

03

Evidence

HumanPresent
AnimalStrong
In-vitroPresent
1999Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic stroke · Gusev EI, Skvortsova VI, Miasoedov NF et al, Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova ↗peer reviewed
2001Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study) · Skvortsova VI, Raevskii KS, Kovalenko AV et al, Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova ↗peer reviewed
2014The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis · Medvedeva EV, Dmitrieva VG, Povarova OV et al, BMC Genomics ↗peer reviewed
2018The efficacy of semax in the treatment of patients at different stages of cerebral ischemia · Asanova LM, Hahn DM, Pak L et al, Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova ↗peer reviewed
04

The honest take

Cognitive enhancement

Strongest claim. Approved in Russia for this purpose. Published human data supports improved attention, memory, and processing in both healthy and impaired populations.

Stroke neuroprotection
Supported

Russian clinical studies show improved outcomes in acute ischemic stroke when Semax is administered alongside standard care. Mechanism (BDNF, cerebral blood flow) is well-supported.

BDNF upregulation
Supported

Confirmed in multiple animal and human studies. BDNF increase is dose-dependent and well-characterized. This is the primary mechanism of cognitive benefits.

05

Interactions & stacking

What's safe to combine, and what belongs in a separate pin.

Safe & synergistic

BPC-157Non-overlapping (cognitive vs tissue repair)
GHK-CuNon-overlapping mechanisms
GHKNon-overlapping mechanisms
AOD-9604Non-overlapping (cognitive vs metabolic)

Keep separate

CJC-1295 with DACDAC maleimide reactivity concern.
06

Side effects & safety

Commonly reported

  • Overstimulation if dosed too high or too late in the day
  • Sleep disruption if administered in the afternoon or evening
  • Mild headache (usually resolves within first few days)
  • Slight appetite changes

Less common & notes

  • Anxiety or irritability at higher doses (reduce dose).
  • Hair loss has been reported anecdotally with prolonged use (mechanism unclear, possibly related to melanocortin receptor effects).
  • Nasal irritation if using intranasal route.
  • Semax does NOT elevate cortisol at standard doses despite being derived from ACTH.
  • Long-term safety data from Russian clinical use is available but may not meet Western standards.
07

Pharmacokinetics

Illustrative plasma concentration · 24 h
Half-life
0.5h
Peak · Tmax
0.33h
Elimination
2.5h
Activity
6-12 hours (BDNF upregulation and cognitive effects outlast plasma presence; cumulative with daily dosing)

Storage. Store unreconstituted vials frozen (-20C) or refrigerated (2-8C). After reconstitution with BAC water, refrigerate at 2-8C. Stable for 28 days. Pro-Gly-Pro C-terminal modification enhances stability against enzymatic degradation. Protect from light.

08

Regulatory status

Approved as a prescription medication in Russia and Ukraine for cognitive disorders, stroke recovery, and neuroprotection. Not FDA-approved in the United States. Available as a research peptide. WADA status: Not specifically listed but may fall under S0 Non-Approved Substances for competitive athletes.

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Go deeper

The guide & community

The complete Semax walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

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