GHRP-2 is a synthetic peptide (a short chain of amino acids) from the family of “growth-hormone-releasing peptides” developed in the 1980s and 1990s by Cyril Bowers's team at Tulane University. It acts as a mimic of ghrelin — the hunger hormone from the stomach — and prompts the pituitary to release growth hormone (GH for short). Unlike most “research peptides”, GHRP-2 has a fair amount of human data: it has been given to healthy volunteers, to children with GH deficiency and to patients in Japan, where under the name pralmorelin it was validated as a diagnostic test. The evidence, however, mostly describes what happens to hormones during the few hours after a dose, not whether long-term use gives anyone a lasting benefit. Below we explain in plain terms what is genuinely known — including the inconvenient findings: rises in cortisol, prolactin and appetite.
What GHRP-2 is
The GHRP family began with GHRP-6, the first hexapeptide that selectively released growth hormone. GHRP-1 and GHRP-2 followed. According to Bowers's 1993 overview, all three had already been given to humans by then, and each successive one released GH more effectively than the last; all of them worked more strongly than the natural GH-releasing hormone (GHRH) and — surprisingly at the time — were also active after oral administration. In Japan GHRP-2 was developed under the code KP-102 and the name pralmorelin.
How it works — the ghrelin switch
GHRP-2 is an agonist (an “activator”) of the ghrelin receptor — a switch on cells that, in humans, is naturally flipped by the hormone ghrelin. Ghrelin does two things: it stimulates growth-hormone secretion and it turns on appetite. GHRP-2 mimics both. It acts both in the pituitary (the small gland beneath the brain that secretes GH) and in the hypothalamus (the part of the brain that controls the pituitary). The result is a short, strong GH pulse — larger than after GHRH alone in human studies, and larger after a higher dose than after a lower one (Arvat et al., 1997). The same switch, however, also sits in the hunger centres and in the stress system, which is where the effects described below come from.
Structure and origin
GHRP-2 is a very short peptide: a handful of amino acids, some of them in the unnatural, “mirror-image” D form, and one — naphthylalanine — that does not occur in human proteins at all. Such elements protect the molecule from rapid breakdown by enzymes, so it survives in the body long enough to act. The Turin group describes GHRP-2 and hexarelin as “super-analogues” of GHRP-6: compounds from the same family with a deliberately reinforced structure. It is not a natural molecule.
What was studied — cells and animals
Animal studies mainly explained where the rise in the stress hormone comes from. In conscious rats, intravenous GHRP-2 (KP-102) raised the level of ACTH — the pituitary hormone that tells the adrenal glands to secrete cortisol. Yet it did not act directly on cultured pituitary cells, and a blocker of CRF (the hypothalamic “corticotropin-releasing factor”) almost abolished the effect. The conclusion of Hirotani's team (2005): GHRP-2 activates the stress axis through the hypothalamus, mainly by releasing CRF. The rise in cortisol is therefore not an accidental impurity but part of the mechanism of action.
Human data — growth hormone and the diagnostic test
This is the strongest part of the literature. In six young adults a single intravenous dose of GHRP-2 produced a strong GH pulse, larger than after GHRH and increasing with dose (Arvat et al., 1997). The diagnostic application was built on this property: if a healthy pituitary answers with a large pulse and a damaged one with a small pulse, growth-hormone deficiency can be told apart that way. The Japanese KP-102 group (Chihara et al., 2007) tested this in 77 healthy people and 58 patients with severe GH deficiency: after an intravenous dose of 100 µg the GH peak averaged 1.4 µg/l in patients and 84.6 µg/l in healthy subjects, the test was reproducible, and a cut-off of 15 µg/l identified the deficiency with high reliability. This is the only use of GHRP-2 backed by formal clinical validation — and it is a single-dose, diagnostic use, not a treatment.
The only longer study of GHRP-2 given with therapeutic intent is the work of Mericq et al. (1998): six children with GH deficiency received subcutaneous GHRP-2 for eight months, at three increasing doses, each for two months. Overnight GH secretion rose with the dose, but the effect of each injection was brief and had almost vanished later in the night. Levels of IGF-I and IGFBP-3 — the “lasting footprint” of growth-hormone action — did not increase. Growth velocity was higher during treatment than before or after it, and no adverse effects were recorded.
Human data — appetite
Because GHRP-2 mimics ghrelin, researchers checked whether it increases eating as ghrelin does. In the study by Laferrère et al. (2005), seven lean, healthy men received a 270-minute subcutaneous infusion of GHRP-2 or saline, followed by an “eat as much as you like” buffet meal. During GHRP-2 they ate on average 35.9% more — every one of them, without exception — while the composition of the meal did not change. In a subsequent double-blind, randomised study (Laferrère et al., 2006) of 19 people, including 9 with obesity, the lower dose increased intake by 10.2% and the higher dose by 33.5% — so the effect was dose-dependent, and obesity did not alter it. This is a well-documented fact: GHRP-2 increases the amount of food people eat.
Human data — cortisol, prolactin and sleep
GHRP-2 is not selective. In the study by Arvat et al. (1997) it raised, in healthy adults, not only GH but also prolactin, ACTH and cortisol. The rise in prolactin was smaller than after TRH (the hormone that releases it “on demand”), but the rise in ACTH and cortisol was similar to that after hCRH — the human hormone that doctors use precisely to stimulate the stress axis in an adrenal test. In short: one dose of GHRP-2 activates the stress axis to a degree comparable with a diagnostic test.
The effect on sleep was examined in one study. Moreno-Reyes et al. (1998) gave seven young men, at night after the third REM period, an intravenous dose of GHRP-2 or placebo. After the peptide there was a brief rise in prolactin and a GH pulse at the upper limit of normal, but sleep did not change — in particular there was no increase in deep sleep (which usually lengthens after GHRH). The only observation was a statistically non-significant tendency towards more wakefulness during the first hour after the injection. The claim that GHRP-2 “improves sleep” therefore has no support in the research; nothing is known about the effect of weeks of use on sleep.
Safety and the limits of the evidence
GHRP-2 is not an approved medicine for treating any disease. The only documented human use is a single-dose diagnostic test. All the studies described above concern single doses or short observation periods in a handful to a dozen or so people; the longest lasted eight months in six children under medical supervision. Practically nothing is known about the safety of many months of use in adults. What is known is that every dose raises cortisol, prolactin and appetite — and chronically elevated cortisol is not harmless to the body. We deliberately give no methods of use and no doses.
The wider context — the GHRP family
GHRP-2 belongs to the group of compounds acting on the ghrelin switch, alongside GHRP-6 (the oldest and the strongest appetite stimulator), hexarelin (with an equally strong GH pulse but a response that fades over time) and ipamorelin, which was created later precisely so as not to touch cortisol and prolactin. A separate group are the GHRH analogues such as CJC-1295, which act on a different switch — in studies the two groups were given together because their effects add up. In the literature the whole GHRP family functions as research and diagnostic tools, not as medicines.
Summary
GHRP-2 is a synthetic ghrelin mimic from the GHRP family with a well-described action in humans: a single dose gives a strong, short growth-hormone pulse while at the same time raising ACTH, cortisol and prolactin and increasing food intake by about a third. Its only validated use is a single-dose diagnostic test for GH deficiency; the only longer study (eight months in six children) showed no rise in IGF-I. Evidence of benefit from long-term use in adults does not exist, whereas evidence of side effects after every dose does.
Sources
- Laferrère B, Hart AB, Bowers CY. Obese subjects respond to the stimulatory effect of the ghrelin agonist growth hormone-releasing peptide-2 on food intake. Obesity (Silver Spring). 2006;14(6):1056–1063. PMID: 16861611. DOI: 10.1038/oby.2006.121. pubmed.ncbi.nlm.nih.gov/16861611
- Moreno-Reyes R, Kerkhofs M, L'Hermite-Balériaux M, et al. Evidence against a role for the growth hormone-releasing peptide axis in human slow-wave sleep regulation. American Journal of Physiology. 1998;274(5):E779–E784. PMID: 9612233. DOI: 10.1152/ajpendo.1998.274.5.E779. pubmed.ncbi.nlm.nih.gov/9612233
- Chihara K, Shimatsu A, Hizuka N, et al.; KP-102 Study Group. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. European Journal of Endocrinology. 2007;157(1):19–27. PMID: 17609397. DOI: 10.1530/EJE-07-0066. pubmed.ncbi.nlm.nih.gov/17609397
- Laferrère B, Abraham C, Russell CD, Bowers CY. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. Journal of Clinical Endocrinology and Metabolism. 2005;90(2):611–614. PMID: 15699539. DOI: 10.1210/jc.2004-1719. pubmed.ncbi.nlm.nih.gov/15699539
- Arvat E, di Vito L, Maccagno B, et al. Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH. Peptides. 1997;18(6):885–891. PMID: 9285939. DOI: 10.1016/s0196-9781(97)00016-8. pubmed.ncbi.nlm.nih.gov/9285939
- Mericq V, Cassorla F, Salazar T, et al. Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children. Journal of Clinical Endocrinology and Metabolism. 1998;83(7):2355–2360. PMID: 9661608. DOI: 10.1210/jcem.83.7.4969. pubmed.ncbi.nlm.nih.gov/9661608
- Hirotani C, Oki Y, Ukai K, et al. ACTH releasing activity of KP-102 (GHRP-2) in rats is mediated mainly by release of CRF. Naunyn-Schmiedeberg's Archives of Pharmacology. 2005;371(1):54–60. PMID: 15645295. DOI: 10.1007/s00210-004-1009-3. pubmed.ncbi.nlm.nih.gov/15645295
- Bowers CY. GH releasing peptides--structure and kinetics. Journal of Pediatric Endocrinology. 1993;6(1):21–31. PMID: 8374685. DOI: 10.1515/jpem.1993.6.1.21. pubmed.ncbi.nlm.nih.gov/8374685
For in-vitro laboratory research only. It is not a human medicine and is not for treatment.