Side-by-side · Research reference

GHRP-2vsPE 22-28

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 2HUMAN-REVIEWED15/42 cited

BAnimal-StrongHUMAN-REVIEWED16/47 cited

GHRP-2

Hexapeptide GHRP · Phase 2 (clinical diagnostic)

100–300 mcgPer doseBowers 1990

Phase 2Evidence levelBowers 1990 Sigalos 2018

~30 minHalf-lifeMalagón 1999

SQ · Multiple sites · 1–3×/day

PE 22-28

TREK-1 Antagonist · Pre-Clinical

0.12 nMTREK-1 IC50Djillani 2017

7 AAPeptide lengthDjillani 2017

AnimalEvidence stage

IP · SQ · Once Daily (animal models)Djillani 2017 Pietri 2019

01Mechanism of Action

Parameter

GHRP-2

PE 22-28

Primary target

Ghrelin receptor (GHS-R1a) on anterior pituitaryBowers 1990

TREK-1 two-pore-domain potassium channelDjillani 2017 Ma 2020

Pathway

GHS-R1a → Gαq → Ca²⁺ → GH vesicle exocytosisBowers 2002

TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity

Downstream effect

Strong GH pulse + IGF-1 elevation; appetite increase via ghrelin agonismBowers 2002

Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017 Cong 2023 Wu 2021

Feedback intact?

Yes, with somatostatin feedback active

N/A — direct ion channel blockade; not receptor-mediated endocrine axis

Origin

Synthetic hexapeptide; developed by Bowers/Tulane group in the 1980sBowers 1990

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 2017 Mazella 2018

Antibody development

—

Not reported in animal studies

02Dosage Protocols

Parameter

GHRP-2

PE 22-28

Standard dose

100–300 mcg per injectionBowers 1990

—

Frequency

1–3× per day

Once daily

Sustained antidepressant effect over 7+ days.

Lower / starter dose

50 mcg per dose

—

Evidence basis

Phase 2 + clinical diagnostic useBowers 1990

Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017 Qi 2018 Wu 2021

Duration

8–12 weeks on / 4 off (anecdotal)

—

Reconstitution

Bacteriostatic water

—

Timing

Pre-sleep + fasted preferred

—

Half-life

~30 minMalagón 1999

—

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

Duration (animal)

—

7–28 days testedQi 2018 Pietri 2019

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

GHRP-2

PE 22-28

Cortisol elevation

Mild but measurableBowers 1990

—

Prolactin elevation

Mild but measurable

—

Hunger

Strong appetite increase

—

Injection site reaction

Mild erythema

—

IGF-1 elevation

Strong; monitor with chronic high-dose use

—

Cancer risk

Contraindicated in active malignancy

—

Pregnancy / OB

Avoid

—

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

GHRP-2

·Active malignancy
·Pregnancy / breastfeeding

PE 22-28

·Human use — no clinical safety data available

Relative Contraindications

GHRP-2

·Untreated diabetes

PE 22-28

·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)

05Administration Protocol

Parameter

GHRP-2

PE 22-28

1. Reconstitution

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL.

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 — abdomen or thigh. 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

Pre-sleep + fasted preferred.

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 ≤30 days.

Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.

5. Needle

29–31G, 4–8 mm insulin syringe.

—

06Stack Synergy

GHRP-2

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

GHRP-2 + CJC-1295-no-DAC is a higher-amplitude alternative to the ipamorelin + CJC-1295 stack. GHRP-2 produces a stronger pulse but with cortisol + prolactin signal — choose when maximum GH amplitude is the goal and the side-effect tolerance is acceptable.

GHRP-2: 100–200 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: High-amplitude GH pulse, body composition

Bowers 1990 Teichman 2006

PE 22-28

— no documented stacks