Side-by-side · Research reference
GHK-CuvsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AHuman-MechanisticHUMAN-REVIEWED8/47 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
GHK-Cu
Tripeptide · Skin / Hair / Wound Healing
SQ or topical · Local · Daily or 2-3×/week
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
GHK-Cu
PE 22-28
Primary target
Copper-dependent enzymes (lysyl oxidase, SOD); regulator of >4000 human genesPickart 2018
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
Cu(II) delivery via GHK chelation → ↑collagen / elastin / GAG synthesis; ↓inflammatory cytokines; ↑hair follicle growth-factor signalingPickart 2018
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Skin firmness + texture improvement, accelerated wound healing, hair regrowth, anti-inflammatory actionPickart 2018Zink 2003
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
Replaces declining endogenous levels
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Endogenous tripeptide first isolated from human plasma; declines from ~200 ng/mL at age 20 to ~80 ng/mL at age 60Pickart 2018
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
—
Not reported in animal studies
02Dosage Protocols
Parameter
GHK-Cu
PE 22-28
Standard SQ dose
1–2 mg / dayPickart 2018
Anecdotal injectable range; topical creams use 0.1–2% solutions.
—
Topical concentration
0.1–2.0% in serum / cream
—
Frequency
Daily or 2–3× per week (SQ)
Once daily
Sustained antidepressant effect over 7+ days.
Lower / starter dose
0.5 mg / day SQ
—
Evidence basis
Human-mechanistic + topical clinical studiesPickart 2018
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Duration
8–12 weeks for visible skin / hair effect
—
Reconstitution
Bacteriostatic water; light-protected
—
Timing
No specific time; evening preferred for topicals
—
Half-life
Hours (estimated; rapid tissue uptake)
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
04Side Effects & Safety
Parameter
GHK-Cu
PE 22-28
Injection site reaction
Erythema, mild pruritus (common)
—
Topical irritation
Mild redness, transient stinging
—
Copper accumulation
Theoretical with very high chronic doses
—
Allergic reaction
Rare hypersensitivity to copper
—
Pregnancy / OB
Avoid topical and SQ — insufficient data
—
Wilson disease
Contraindicated
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
GHK-Cu
- ·Wilson disease (copper-overload disorder)
- ·Pregnancy / breastfeeding
- ·Known copper hypersensitivity
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
GHK-Cu
- ·Hemochromatosis (copper-iron crosstalk theoretical)
- ·Concurrent copper-chelator therapy
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
GHK-Cu
PE 22-28
1. Reconstitution
Add 1–2 mL bacteriostatic water to a 50 mg vial → 25–50 mg/mL. Use within 30 days, refrigerated.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Injection site
SQ — local to the area of interest (face, scalp) for skin / hair indications. Rotate sites.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Timing
Anytime; evening preferred. Topical: apply to clean dry skin.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Storage
Lyophilised: room temp, light-protected. Reconstituted: refrigerate, light-protected, ≤30 days.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
5. Needle
30–31G, short (4–6 mm) for shallow SQ. Topical: clean fingertips, no needle.
—
06Stack Synergy
GHK-Cu
+ BPC-157
ModerateGHK-Cu drives ECM remodelling and copper-dependent enzymes; BPC-157 upregulates VEGFR2 angiogenesis and fibroblast migration. The pathways are non-overlapping and complementary — together they accelerate wound healing more than either alone in anecdotal protocols.
- GHK-Cu
- 1–2 mg SQ · daily near wound
- BPC-157
- 250–500 mcg SQ · daily near wound
- Primary benefit
- Combined ECM rebuilding + angiogenesis for tissue repair
PE 22-28
— no documented stacks