Humanin vs Semax

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

HumaninSemax
CategoryPeptidesPeptides
Standard DoseResearch indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established.Research indicates 200-600 mcg daily via intranasal administration (0.1% solution, 2-3 drops per nostril).
TimingNo established timing protocol. Morning dosing suggested for neuroprotective applications.Morning and early afternoon dosing (avoid evening — may cause stimulation/insomnia). Intranasal preferred for rapid CNS delivery.
Cycle DurationExperimental — no established cycle lengths.10-14 day cycles with equal rest periods. Some protocols use 3-5 day on / 2 day off patterns.
Evidence Levelanimal_plus_anecdotalmoderate_human
A

Humanin

Peptides

Mechanism

Humanin is a 24-amino acid mitochondrial-derived peptide encoded by the 16S rRNA gene of mitochondrial DNA. It binds IGFBP-3 with high affinity (via Phe-6), interfering with IGFBP-3 binding to importin-beta and suppressing IGFBP-3-mediated apoptosis. It also inhibits the pro-apoptotic protein Bax (Bcl-2 family), preventing mitochondrial outer membrane permeabilization and intrinsic apoptosis. Humanin and IGFBP-3 synergistically protect neurons from amyloid-beta-induced apoptosis, and it activates the STAT3 and ERK1/2 pathways for cytoprotection.

Standard Dosing

Research indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established.

Timing

No established timing protocol. Morning dosing suggested for neuroprotective applications.

Cycle Duration

Experimental — no established cycle lengths.

Side Effects

  • Limited data on side effects in humans
  • Theoretical: interference with normal apoptotic processes

Contraindications

  • Active cancer (anti-apoptotic effects could support tumor survival)
  • Pregnancy and breastfeeding

Best Stacking Partners

MOTS-cEpitalonSS-31
B

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

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