Skip to content

Cognitive & Neuroprotective

Semax

Russian ACTH-derived nasal peptide that raises BDNF; studied for stroke recovery and focus, with small human trials.

RestrictedEvidence level 3 of 5: Limited human dataAlso: Met-Glu-His-Phe-Pro-Gly-Pro, ACTH(4-7)-PGP, N-acetyl Semax (variant)

Overview

Semax is a seven-amino-acid peptide built from the 4–7 fragment of adrenocorticotropic hormone (ACTH) plus a stabilizing Pro-Gly-Pro tail. It keeps ACTH's brain-related effects but has no meaningful effect on cortisol. Developed in Russia, it is approved there as a nasal spray for ischemic stroke, transient ischemic attacks and cognitive disorders. Studies show it rapidly increases BDNF and its receptor TrkB in the hippocampus, modulates dopamine and serotonin signaling and protects neurons under ischemic stress. Small clinical trials report improved motor and cognitive recovery after stroke and better attention under stress. The evidence is encouraging but limited by small sample sizes and limited independent replication, so it remains an investigational therapy in the U.S.

Classification
Synthetic heptapeptide (ACTH 4–10 analog without hormonal activity)
Route
Intranasal (subcutaneous less common)
Half-life
Minutes in plasma; CNS effects persist up to ~24 hours

Mechanism of action

Primary targetMelanocortin-related CNS signaling; BDNF/TrkB upregulation
  1. Intranasal deliveryRapid nose-to-brain transport; detectable CNS effects within minutes.
  2. BDNF and TrkB riseHippocampal and cortical BDNF expression increases within hours.
  3. Dopamine/serotonin modulationEnhances dopaminergic and serotonergic tone tied to motivation and attention.
  4. Ischemic neuroprotectionDampens excitotoxic and inflammatory gene programs after ischemia.
  5. Plasticity and recoverySupports synaptic plasticity, aiding cognitive and motor recovery.
Downstream effects
  • Post-stroke recovery
  • Attention and memory
  • Stress resilience

Researched for

  • Ischemic stroke recovery
  • Cognitive impairment
  • Attention / ADHD
  • Optic nerve disease
  • Stress-related cognitive fatigue

Research notes

  • Gusev et al. reported improved neurological recovery in acute ischemic stroke with intranasal Semax in Russian trials.
  • Dolotov et al. (2006) showed rapid BDNF and TrkB upregulation in rat hippocampus.
  • FDA advisory committee voted 8–5 (July 2026) to recommend Semax for the 503A bulks list; FDA staff had recommended against.
  • No large, randomized, placebo-controlled trials outside Russia.

Reported side effects

  • Nasal irritation
  • Headache
  • Irritability or overstimulation at higher doses
  • Insomnia if dosed late

Contraindications & cautions

  • Mania or hypomania
  • Acute psychosis
  • Uncontrolled hypertension (relative)
  • Pregnancy and breastfeeding

Lab monitoring

  • CBC, CMP
  • Liver enzymes
  • Thyroid panel (TSH, free T4)
  • Vitamin B12, folate, vitamin D
  • Baseline cognitive assessment

Dosing and pricing for Semax

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

Ready to take control of your health?

Start with a 60-minute physician evaluation, virtually in seven states or in person in Reston, Virginia.

Request a consultation 703-400-5314

Cash-pay. HSA and FSA accepted. Monday–Friday, 10 AM – 2 PM (virtual and in person).