Semax vs SS-31 (Elamipretide)

Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.

SemaxSS-31 (Elamipretide)
CategoryPeptidesPeptides
Standard DoseResearch indicates 200-600 mcg daily via intranasal administration (0.1% solution, 2-3 drops per nostril).Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.
TimingMorning and early afternoon dosing (avoid evening — may cause stimulation/insomnia). Intranasal preferred for rapid CNS delivery.Morning dosing preferred. No food timing restrictions.
Cycle Duration10-14 day cycles with equal rest periods. Some protocols use 3-5 day on / 2 day off patterns.Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.
Evidence Levelmoderate_humanEmerging (Phase 2/3 trials)
A

Semax

Peptides

Mechanism

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analog of the ACTH(4-10) fragment that rapidly upregulates brain-derived neurotrophic factor (BDNF) and its signaling receptor TrkB in the hippocampus (1.4-fold BDNF protein increase, 3-fold exon III BDNF mRNA increase). It activates dopaminergic and serotonergic brain systems, enhances neurotrophin gene expression (BDNF, NGF), and modulates intracellular calcium dynamics in brain neurons. Semax lacks ACTH's corticotropic activity, acting purely as a nootropic/neuroprotective agent.

Standard Dosing

Research indicates 200-600 mcg daily via intranasal administration (0.1% solution, 2-3 drops per nostril).

Timing

Morning and early afternoon dosing (avoid evening — may cause stimulation/insomnia). Intranasal preferred for rapid CNS delivery.

Cycle Duration

10-14 day cycles with equal rest periods. Some protocols use 3-5 day on / 2 day off patterns.

Side Effects

  • Nasal irritation (intranasal route)
  • Mild headache
  • Stimulation/insomnia if dosed late
  • Irritability at high doses
  • Hair loss (anecdotal at high doses)

Contraindications

  • Seizure disorders
  • Acute psychosis or mania
  • Pregnancy and breastfeeding
  • Severe hypertension

Best Stacking Partners

SelankP21Noopept

Mechanism

SS-31 (D-Arg-Dmt-Lys-Phe-NH2, also known as elamipretide/Bendavia) is a cell-permeable tetrapeptide that localizes to the inner mitochondrial membrane and binds cardiolipin via electrostatic interactions. This stabilizes cardiolipin against oxidative damage, preserving cristae integrity, reducing ROS production, and maintaining mitochondrial ATP production. SS-31 interacts with proteins in two functional groups: oxidative phosphorylation complexes and 2-oxoglutarate metabolic enzymes — all known cardiolipin binders. It restores mitochondrial function without acting as a direct antioxidant.

Standard Dosing

Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.

Timing

Morning dosing preferred. No food timing restrictions.

Cycle Duration

Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.

Side Effects

  • Injection site reactions
  • Headache
  • Diarrhea (in clinical trials)
  • Nausea

Contraindications

  • Pregnancy and breastfeeding
  • Severe renal impairment (peptide clearance concern)
  • Not commercially available
  • Clinical trial participants only

Best Stacking Partners

MOTS-cHumaninEpitalon

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