tuneTypical Dose
200–600 mcg/day intranasal (0.1% solution, 2–3 drops per nostril, 2–3x daily)
Peptide
Semax
ACTH(4-10) peptide analogue
Evidence TierCWADA NOT PROHIBITED
watchEffect Window
Weeks to months in post-stroke observational periods
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Semax is a synthetic peptide derived from an ACTH fragment used in some regions for neurologic recovery. It is used for cognitive and neuroprotective claims, with evidence concentrated in regional studies.
Regional clinical studies suggest improved outcomes after stroke and improvements in some cognitive measures, with proposed neurotrophic and antioxidant mechanisms. Some users report reduced fatigue and improved attention. Minority research explores anxiety reduction and optic nerve protection in experimental settings. Broader validation is limited by few large modern randomized trials and heterogeneous study designs.
Potential neuroprotective and neurotrophic pathway modulation in ischemic models, with limited human translation.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Post-stroke recovery signal (Barthel/motor outcome) with limited clinical evidence.
- Neurotrophic and anti-inflammatory support signals in preclinical ischemia models.
Secondary Outcomes
- Not established for healthy users or broad nootropic outcomes.
Safety
Contraindications and Interactions
Contraindications
- Pregnancy or lactation
- Unstable psychiatric or neurologic disease
- Uncontrolled endocrine, liver, kidney, or severe cardiovascular disease
Side effects
- Insufficient standardized evidence for frequent adverse profile. Injection/local irritation and mild effects reported in legacy use
Interactions
- Not well characterized
Avoid if
- Pregnancy
- Childhood
- Poor-quality/illicit sourcing
Evidence
Study-level References
semax-SRC-001Clinical trial (ischemic stroke)
Sourceopen_in_newhttps://pubmed.ncbi.nlm.nih.gov/29798983/ doi:10.17116/jnevro20181183261-68
Population: Adults after ischemic stroke (n=110)
Dose protocol: Semax regimen used in stroke protocol. 10-day treatment segments reported.
Key findings: Directional improvement in motor and BDNF outcomes was observed in treatment group in reported trial.
Notes: Single trial, older local publication context, limited replication.
Paper content
Directional improvement in motor and BDNF outcomes was observed in treatment group in reported trial.
semax-SRC-002Animal preclinical study (ischemic model)
Sourceopen_in_newhttps://pubmed.ncbi.nlm.nih.gov/19633950/ doi:10.1007/s10571-009-9432-0
Population: Rats with induced cerebral ischemia
Dose protocol: Semax treatment after ischemic injury in controlled preclinical design
Key findings: Increased neurotrophic signaling and reduced injury markers compared with controls.
Notes: Mechanistic support only. Does not establish human dosing or effectiveness.
Paper content
Increased neurotrophic signaling and reduced injury markers compared with controls.
semax-SRC-003Animal preclinical study
Sourceopen_in_newhttps://pubmed.ncbi.nlm.nih.gov/34201112/
Population: Rodent ischemia model
Dose protocol: ACTH-derived peptide treatment in acute stroke model
Key findings: Neuroinflammatory marker suppression and improved receptor signaling were observed.
Notes: Useful for mechanism confidence only.
Paper content
Neuroinflammatory marker suppression and improved receptor signaling were observed.
semax-SRC-004In vitro mechanistic study using artificial membrane models.
Sourceopen_in_newSciacca MFM, Naletova I, Giuffrida ML, Attanasio F. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models. ACS Chem Neurosci. 2022;13(4):486-496. doi:10.1021/acschemneuro.1c00707. PMID:35080861.
Population: In vitro model systems using amyloid-beta peptide and artificial membrane preparations.
Dose protocol: Semax applied to copper-complexed amyloid-beta in artificial membrane systems
Key findings: Semax prevented Abeta-Cu2+ complex formation and inhibited fibrillogenesis, showing anti-aggregating properties in the presence of copper ions.
Notes: In vitro mechanistic data only. Relevance to neurodegeneration in humans is speculative.
Paper content
This in vitro study examined whether Semax could influence amyloid-beta aggregation in the context of copper binding, a process implicated in Alzheimer's disease pathology. Using spectrofluorometric, calorimetric, and cellular assays, the researchers found that Semax prevented formation of Abeta-Cu2+ complexes and exhibited anti-aggregating and protective properties, especially in the presence of copper ions. The peptide disrupted the fibrillogenesis pathway and reduced oligomeric species formation. This is mechanistic evidence only and does not establish any clinical utility for Semax in neurodegeneration. No human data are available for this application.
semax-SRC-005Preclinical animal study using RNA sequencing.
Sourceopen_in_newFilippenkov IB, Stavchansky VV, Denisova AE, et al. Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes (Basel). 2020;11(6):681. doi:10.3390/genes11060681. PMID:32580520.
Population: Rat model of cerebral ischemia-reperfusion injury.
Dose protocol: Semax administered after cerebral ischemia-reperfusion in rats, analyzed by RNA sequencing
Key findings: Identified 394 differentially expressed genes. Semax suppressed inflammatory gene expression and activated neurotransmission-related genes after ischemic injury.
Notes: Transcriptome-level mechanistic support for neuroprotection. Preclinical only.
Paper content
This preclinical study used RNA sequencing to characterize gene expression changes induced by Semax peptide after cerebral ischemia-reperfusion in rats. Treatment with Semax produced 394 differentially expressed genes (greater than 1.5-fold change). The peptide suppressed expression of genes related to inflammatory processes and activated expression of genes involved in neurotransmission, contrasting with the expression pattern seen in untreated ischemia-reperfusion injury. This provides transcriptome-level mechanistic evidence supporting Semax's neuroprotective properties in stroke models but does not establish human clinical efficacy.