Side-by-side · Research reference

IpamorelinvsPE 22-28

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

APhase 1HUMAN-REVIEWED21/57 cited

BAnimal-StrongHUMAN-REVIEWED16/47 cited

Ipamorelin

Selective GHRP · Ghrelin Mimetic

200–300 mcgPer doseRaun 1998

Phase 1Evidence levelRaun 1998 Sigalos 2018

~2 hrHalf-lifeRaun 1998

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

Ipamorelin

PE 22-28

Primary target

Ghrelin receptor (GHS-R1a) on anterior pituitaryRaun 1998

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

Pathway

GHS-R1a binding → Gαq/11 → ↑intracellular Ca²⁺ → GH vesicle exocytosisRaun 1998 Bowers 1991

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

Downstream effect

GH pulse amplification, IGF-1 elevation, recovery and lipolytic effectsBowers 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 — pulsatile pattern preserved; somatostatin feedback activeBowers 2002

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

Origin

Pentapeptide H-Aib-His-D-2-Nal-D-Phe-Lys-NH₂; rationally designed for ghrelin-receptor selectivityRaun 1998

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 short-term studies

Not reported in animal studies

02Dosage Protocols

Parameter

Ipamorelin

PE 22-28

Standard dose

200–300 mcg per injectionRaun 1998

Anecdotal community range; clinical doses 1–3 mg IV in trials.

—

Frequency

1–3× per day

Once daily pre-sleep is most common; twice or thrice for advanced users.

Once daily

Sustained antidepressant effect over 7+ days.

Lower / starter dose

100 mcg per dose

—

Evidence basis

Phase 1 + clinical practiceRaun 1998 Sigalos 2018

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

Duration

8–12 weeks on / 4 weeks off (anecdotal)

GHS-R desensitisation reported with continuous dosing.

—

Reconstitution

Bacteriostatic water; typical 2 mL per 5 mg vial

—

Timing

Pre-sleep + fasted preferred; 30 min away from food

—

Half-life

~2 hoursRaun 1998

Longer than GHRP-6 (15 min); shorter than CJC-1295-DAC (~8 days).

—

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

Ipamorelin

PE 22-28

Cortisol elevation

Negligible vs other GHRPsRaun 1998

—

Prolactin elevation

NegligibleRaun 1998

—

Hunger

Mild appetite increase via ghrelin-receptor crosstalk

—

Injection site reaction

Mild irritation possible

—

GH excess (overdose)

Joint pain, edema, insulin resistance

—

IGF-1 elevation

Dose-dependent; monitor with chronic high-dose use

—

Cancer risk

Theoretical via GH/IGF-1 axis; 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

Ipamorelin

·Active malignancy or cancer history
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

PE 22-28

·Human use — no clinical safety data available

Relative Contraindications

Ipamorelin

·Untreated diabetes
·Severe insulin resistance
·Concurrent corticosteroid use (theoretical desensitisation)

PE 22-28

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

05Administration Protocol

Parameter

Ipamorelin

PE 22-28

1. Reconstitution

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL. Roll gently. Solution should be clear.

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

Subcutaneous, abdomen or thigh. Rotate sites. Pinch fat for shallow SQ delivery.

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 optimal — aligns with natural GH pulse. Some protocols add a morning fasted dose.

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, protected from light. Reconstituted: refrigerate 2–8 °C, use within 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.

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06Stack Synergy

Ipamorelin

+ Tesamorelin

Strong

View Tesamorelin →

Ipamorelin (GHRP) + tesamorelin (GHRH analogue) is the textbook dual-axis GH stack. They activate two distinct pituitary receptors — the ghrelin receptor and the GHRH receptor — producing a synergistic GH pulse larger than either alone. Ipamorelin's selectivity (no cortisol/prolactin spike) makes it the ideal GHRP partner for long-term protocols.

Ipamorelin: 200–300 mcg SQ · pre-sleep
Tesamorelin: 2 mg SQ · same injection · pre-sleep
Primary benefit: Maximal GH pulsatility, fat loss, recovery, sleep depth

Raun 1998 Bowers 2002

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

CJC-1295 (no DAC) is a short-acting GHRH analogue. Combined with ipamorelin (GHRP), the pulse is amplified across both receptor systems with timing similar to native physiology. Without the DAC modification, the stack maintains sharp peaks rather than the sustained elevation seen with CJC-1295-DAC + ipamorelin.

Ipamorelin: 200–300 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation matching physiological pattern

Teichman 2006 Ionescu 2006

PE 22-28

— no documented stacks