Semax
peptide · headlineResearch use onlyModulates neurotransmitter levels by increasing dopamine and serotonin availability
Overview
Semax is a synthetic ACTH-derived neuropeptide used for its cognitive-enhancing, neuroprotective, and antidepressant effects. Developed in Russia, it modulates neurotransmitters and neurotrophic factors like BDNF. It is used in cognitive decline, stress recovery, stroke rehabilitation, and neuropsychiatric disorders in both animal models and limited human trials.
How it works
- Modulates neurotransmitter levels by increasing dopamine and serotonin availability
- Upregulates BDNF (brain-derived neurotrophic factor), enhancing synaptic plasticity
- Exerts antioxidant effects, reducing oxidative stress and neuroinflammation
- Influences melanocortin receptors involved in cognition, emotion, and immune modulation
Dosing
0.1 mg intranasally 2–3 times daily for 10–14 days per cycle. Repeatable as needed with breaks.
Caution: In Russian clinical use, doses of 300–600 μg intranasally are reported. These regimens are not approved or validated in the U.S. or other regions without regulatory approval.
Cycling
- Used 2–3 times daily for 10–14 days. Repeat cycles every 1–3 months based on cognitive or stress recovery goals.
Side effects
- Common
- Headache, restlessness, slight BP fluctuations
Stacking & combinations
- With
N-Acetyl Selank Amidate
- Benefit
Works synergistically with Selank for anxiolytic and cognitive stability
- With
PACAP
- Benefit
Boosts neurotrophic and anti-inflammatory effects when paired with PACAP
- With
Cortexin
- Benefit
Complements Cortexin in neurodegenerative and stroke recovery protocols
Lifestyle support
- Diet
Balanced diet rich in antioxidants.
- Sleep
Quality sleep. Stress management.
- Timing
Morning intranasal dosing for focus throughout the day.
- Exercise
Regular mental stimulation and exercise.
Research studies
Studies summarized for educational purposes only. Inclusion does not imply human use; referenced research was conducted in vitro, in animal models, or in regulated clinical trials.
Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action
Shadrina M, Kolomin T, Agapova T, Agniullin Y, Shram S, Slominsky P, Lymborska S, Myasoedov N. J Mol Neurosci. 2010 May;41(1):30–35. View source ↗
This in vivo study in male Wistar rats characterized the time-course of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in three central nervous system regions — hippocampus, frontal cortex, and retina — at 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h after Semax administration. Expression levels were quantified by real-time PCR. The authors reported multidirectional, region- and time-dependent modulation of both neurotrophin genes: a transient decrease in hippocampal and retinal NGF/BDNF mRNA at 20 min, an increase in frontal cortex at the same early time point, and a significant rise in retinal BDNF expression by 90 min. These data were interpreted as evidence that Semax engages the neurotrophin system through coordinated regional transcriptional dynamics rather than a single uniform upregulation.
Researchers gave Semax to rats and measured the activity of two genes — NGF and BDNF — that produce proteins which help brain cells survive and form new connections. They looked at three brain-related regions (the memory center, the front of the brain, and the retina) at several time points. They found that Semax did not simply turn these genes "up" everywhere — instead, it shifted their activity in different directions in different regions at different times. The pattern is consistent with Semax acting as a regional signal that retunes neurotrophin production rather than a blanket booster.
Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents
Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grieb P, Rayevsky KS. Neurochem Res. 2005 Dec;30(12):1493–1500. View source ↗
This rodent study examined Semax's effect on central monoaminergic systems. Using microdialysis and tissue measurements, the authors reported that Semax administration was associated with positive modulation of the striatal serotonergic system and an enhanced striatal release of dopamine, as well as potentiation of locomotor behavior elicited by D-amphetamine. The findings linked Semax's previously documented nootropic profile to measurable changes in dopaminergic and serotonergic neurotransmission, providing a mechanistic bridge between the peptide's structural derivation from ACTH(4-10) and its observed behavioral effects in rodent models.
Scientists looked at what Semax does to two of the brain's main chemical messenger systems — dopamine and serotonin — in rats and mice. They found that Semax increased the release of dopamine in a brain region called the striatum and boosted serotonin signaling there as well. When they gave the animals amphetamine (which itself increases dopamine), Semax made the movement-related response stronger. This suggests Semax doesn't act on a single isolated target — it tunes several of the brain's chemical signaling systems at once.
Verified citations
2 · PubMed-checked- Semax peptide targets the mu opioid receptor gene to promote recovery after spinal cord injury.mechanismPMID 40692165 ↗
- The peptide semax affects immune and vascular gene expression in rat brain focal ischemia.preclinicalPMID 24661604 ↗
Reconstitution
Refrigerate at 2–8°C
Chemistry & PK
- Sequence
- Met-Glu-His-Phe-Pro-Gly-Pro
- Half Life
- Likely short (minutes in plasma); CNS effects persist longer due to gene regulation
- Degradation
- Metabolized by tissue peptidases
- Molecular Weight
- 813.93
- Molecular Formula
- C37H51N9O10S
- Tissue Specificity
- Primarily acts in the brain: hippocampus, cortex, hypothalamus
Bioavailability
- In
- High CNS bioavailability via olfactory and trigeminal nerve transport
- Oral
- Very poor due to enzymatic degradation in the GI tract
- Subq
- Not commonly used; intranasal route preferred for CNS targeting
Storage & handling
- Lyophilized
Freeze until mixing (−20°C)
- Reconstituted
Refrigerate at 2–8°C
Legal / compounding
- EU
- Not Approved
- FDA
- Not Approved
- Canada
- Not Approved
- Australia
- Not Approved
Legal status is a hard gate: non-compoundable or delisted agents cannot be filled and are blocked from protocol export. Keep 503A status current.