Side-by-side · Research reference
SemaxvsSS-31
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AHuman-MechanisticDraft12/39 cited
BPhase 3Reviewed9/43 cited
Semax
Cognitive enhancer · Russian Pharma
Intranasal · 2–3×/day during cognitive demand
SS-31
Cardiolipin-binding · Mitochondrial protective
SQ · Abdomen · Once daily
01Mechanism of Action
Parameter
Semax
SS-31
Primary target
BDNF / NGF expression + monoamine modulationKaplan 2017
Cardiolipin in inner mitochondrial membraneSzeto 2014
Pathway
↑ BDNF + NGF synthesis + 5-HT modulation → neuroplasticity + anxiolysis + cognitive enhancementKaplan 2017
Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014Szilagyi 2009
Downstream effect
Improved memory + attention; reduced anxiety; neuroprotection in ischemiaKaplan 2017
Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014
Feedback intact?
—
—
Origin
Synthetic 7-AA peptide derived from ACTH(4-7) with C-terminal Pro-Gly-Pro stabilising tailKaplan 2017
Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014
Antibody development
—
—
02Dosage Protocols
Parameter
Semax
SS-31
Standard dose
200–600 mcg / dose intranasalKaplan 2017
40 mg / day SQ (clinical trials)Szeto 2014
Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.
Frequency
2–3× per day during cognitive demand
Once daily
Lower / starter dose
100 mcg / dose
5 mg / day (anecdotal)
Evidence basis
Human-mechanistic + Russian clinicalKaplan 2017
Multiple Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014Szilagyi 2009
Duration
10–14 day cycles, repeated PRN
Indefinite for mitochondrial disease; cycled for healthspan use
Reconstitution
Pre-formulated nasal spray (commercial); research vial: bacteriostatic water
Bacteriostatic water
Timing
Morning + early afternoon
Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress
Half-life
Short plasma; CNS effect lasts ~3–6 hr
~3 h plasma; tissue uptake longer
04Side Effects & Safety
Parameter
Semax
SS-31
Nasal irritation
Mild burning or congestion (transient)
—
Sleep disruption
Late-day dosing may interfere with sleep
—
Headache
Uncommon, transient
Reported in some Phase 3 trials
Long-term safety
Limited Western RCT data
Phase 3 data over 24+ months; no major safety signalsSzeto 2014
Pregnancy / OB
Avoid
Avoid — insufficient data
Injection site reaction
—
Erythema, mild pruritus
GI symptoms
—
Nausea (uncommon)
Cardiovascular
—
Cardio-protective in studies; no signal of harm
Absolute Contraindications
Semax
- ·Pregnancy / breastfeeding
SS-31
- ·Pregnancy / breastfeeding
- ·Hypersensitivity to peptide
Relative Contraindications
Semax
- ·Active psychiatric instability
- ·Concurrent strong stimulants
SS-31
- ·None established
05Administration Protocol
Parameter
Semax
SS-31
1. Form
Pre-formulated nasal spray (commercial) or research vial reconstituted with bacteriostatic water.
Add bacteriostatic water per label. Light-protected handling.
2. Administration
Intranasal — 2–3 sprays per nostril per dose. Tilt head slightly back.
SQ — abdomen or thigh. Rotate sites.
3. Timing
Morning + early afternoon. Avoid evening (sleep disruption).
Morning fasted; pre-workout for exercise-augmented mitochondrial stress.
4. Storage
Refrigerate after reconstitution; light-protected.
Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.
5. Caveat
Cycle on/off to avoid neurochemical adaptation.
29–31G, 4–8 mm insulin syringe.
06Stack Synergy
Semax
+ Selank
ModerateSemax (cognitive enhancer, BDNF/NGF) and Selank (anxiolytic + immune) form the canonical Russian "neuro stack" — both intranasal peptide bioregulators with complementary axes. Semax for cognitive demand; Selank for stress mitigation.
- Semax
- 200–600 mcg intranasal · morning + afternoon
- Selank
- 150–300 mcg intranasal · midday + early evening
- Primary benefit
- Cognitive enhancement + stress mitigation
SS-31
+ MOTS-c
ModerateSS-31 and MOTS-c address mitochondrial decline through complementary axes. SS-31 protects existing mitochondrial structure (cardiolipin binding, cristae stabilisation). MOTS-c upregulates AMPK/PGC-1α, triggering biogenesis of new mitochondria. Together they pair preservation with renewal — anecdotally favoured in healthspan and post-cardio-event recovery protocols.
- SS-31
- 5–10 mg SQ · daily morning
- MOTS-c
- 5 mg SQ · 2× per week pre-workout
- Primary benefit
- Mitochondrial preservation + biogenesis