Growth Hormone
Pentapeptide GHRP
A selective growth hormone secretagogue studied for clean GH pulses without prolactin or cortisol elevation.
Ipamorelin is a pentapeptide ghrelin mimetic that triggers growth hormone release with a cleaner side-effect profile than older GHRPs. Often combined with CJC-1295 in research protocols. Studied for body composition and sleep quality.
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Evidence level
Preclinical only
A pentapeptide ghrelin receptor agonist that triggers pulsatile growth hormone release with notably less prolactin, cortisol, and ACTH stimulation than older GHRPs. Most evidence is preclinical and from short pharmacokinetic studies.
Mechanism
Activates the ghrelin receptor to release GH from the pituitary.
Researched benefits
Selective GH secretagogue
In healthy volunteer PK studies, ipamorelin produces GH pulses comparable to GHRP-6 and GHRP-2 but without the parallel rise in prolactin, ACTH, or cortisol seen with the older compounds. The selectivity comes from clean GHS-R1a agonism without off-target activity.
Synergy with GHRH analogs
Co-administration with CJC-1295 (or sermorelin) produces larger GH pulses than either agent alone — the two mechanisms (releasing somatotrophs vs amplifying release) are complementary. This is the most common research stack.
Body composition changes (preclinical)
Rodent studies show modest increases in lean mass and bone growth with chronic administration. Effects are consistent with elevated IGF-1 from sustained GH pulses.
Sleep architecture
GH is normally pulsed during slow-wave sleep. Anecdotal and small-cohort reports describe improved deep-sleep duration with evening dosing, consistent with reinforcing the natural overnight GH pulse.
Risks & cautions
IGF-1 elevation
Sustained use raises IGF-1. Supraphysiologic IGF-1 is associated theoretically with proliferative effects; the long-term clinical significance at typical research doses is unknown.
Appetite increase
Ghrelin receptor agonism modestly increases hunger in some users. Effect is usually mild and tolerable but can be counterproductive for fat-loss goals.
Water retention and joint discomfort
Classic GH-related side effects: mild edema, carpal-tunnel-like paresthesias, and joint stiffness can appear at higher doses, particularly when stacked with CJC-1295.
Limited long-term human data
Original development as a treatment for postoperative ileus was discontinued. There are no large long-term safety trials in healthy adults.
Dosing
100–300 mcg subcutaneously, 1–3 times daily, often timed pre-sleep and/or post-workout. Typically run in 8–12 week cycles.
Vial sizes
2mg / 5mg
Half-life
~2 hours
Route
subcutaneous
Reconstitute with bacteriostatic water; refrigerate. Half-life is ~2 hours, so multiple daily doses are required to maintain pulses. Inject on an empty stomach — postprandial somatostatin blunts the GH response.
Contraindications
In depth
Ipamorelin was developed by Novo Nordisk in the late 1990s as part of a search for a clean growth hormone secretagogue — older GHRPs (GHRP-2, GHRP-6, hexarelin) released GH effectively but also raised prolactin, ACTH, and cortisol, which limited their clinical utility.
The compound is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) and acts as an agonist at the ghrelin/growth hormone secretagogue receptor (GHS-R1a). Its claim to fame is receptor selectivity: it triggers somatotroph GH release without the off-target activation that drives prolactin and HPA-axis effects in the older peptides.
Clinical development for postoperative ileus and short bowel syndrome was discontinued, so ipamorelin never reached approval. It persists in the research-peptide market as a popular GH-secretagogue, almost always paired with a GHRH analog.
Ipamorelin binds GHS-R1a on pituitary somatotrophs and on hypothalamic neurons. Downstream:
Because it preserves pulsatility and respects negative feedback, ipamorelin is considered "physiologic" in a way that exogenous rhGH is not.
The human dataset is thin but real:
There are no large long-term trials in healthy adults using ipamorelin for body composition or longevity goals.
Robust. Rodent studies replicated GH release, IGF-1 elevation, bone growth, and modest lean-mass effects across multiple labs. Selectivity vs prolactin/ACTH was confirmed in dog and primate models.
The canonical research stack is ipamorelin + CJC-1295 (with or without DAC). The mechanistic rationale is solid — GHRH amplifies the pulse that ipamorelin triggers. Both have short half-lives without DAC, so 2–3× daily dosing is typical.
Other common stacks:
Avoid stacking with anything that raises cortisol or prolactin if the goal is to preserve ipamorelin's clean profile.
References
