GHRP-2 (Pralmorelin): synthetic peptide that triggers growth hormone release

What this is

GHRP-2 (Growth Hormone Releasing Peptide-2), also called pralmorelin or the development code KP-102, is a small synthetic peptide that makes the pituitary gland release a pulse of growth hormone. It is a six-residue peptide built around three D-amino acids and an unnatural aromatic residue (D-Ala–D-2-naphthylalanine–Ala–Trp–D-Phe–Lys with a C-terminal amide cap); the stored one-letter string DAWAFK is an approximation that does not convey the D-form residues, the non-standard β-naphthylalanine at position 2, or the amide terminus. GHRP-2 works by mimicking the body's own hunger hormone ghrelin at a single receptor (the growth hormone secretagogue receptor, GHSR-1a), and its primary established use today is as a clinical diagnostic agent — given as a one-off intravenous injection to test whether someone's pituitary can still release growth hormone on demand.

Outside that diagnostic context, GHRP-2 has been used in the bodybuilding and wellness peptide market as a "natural" GH-elevation tool, often stacked with a GHRH-class analog. It is not approved as a therapeutic drug in the United States, the EU, the UK, Canada or Australia. Its only formal pharmaceutical approval anywhere is in Japan, where it was authorised by the PMDA in October 2004 (pralmorelin / GHRP Kaken, Kaken Pharmaceutical) as an intravenous diagnostic test for growth-hormone deficiency.

History

GHRP-2 belongs to a research line that began in the late 1970s at Tulane University, where endocrinologist Cyril Bowers and chemist Frank Momany noticed that certain modified enkephalin-derived peptides released growth hormone without any of the expected opioid activity. The first published compound from that program, GHRP-6, appeared in 1984 (reviewed in Bowers, Comprehensive Physiology 1998). GHRP-2 was synthesised as a more potent successor — a hexapeptide built from D-amino acids and an unnatural naphthylalanine residue to resist proteolysis and bind the (then unknown) GH-releasing receptor more tightly.

These compounds were the puzzle that led to a real receptor discovery: Howard and colleagues cloned the growth hormone secretagogue receptor (GHSR) from human and porcine pituitary in 1996 (Howard et al., Science 1996) using GHRP-class ligands as the affinity probe. Three years later Kojima and colleagues isolated the receptor's natural ligand from the stomach and named it ghrelin (Kojima et al., Nature 1999). GHRP-2 — alongside its sister molecules — is therefore one of the synthetic peptides that triggered the discovery of an entirely new endocrine axis.

The peptide was advanced toward the clinic by Kaken Pharmaceutical in Japan (initially under the code KP-102) and was approved by the Japanese PMDA in October 2004 under the name pralmorelin (brand name GHRP Kaken) as an intravenous diagnostic test for growth-hormone deficiency. Outside Japan, Phase 2 development for GH-deficiency and short-stature indications was investigated and discontinued without market approval (Pralmorelin review, Drugs in R&D 2004).

What it does

A single dose of GHRP-2 produces a sharp, time-limited spike in circulating growth hormone, similar in shape to the pulses the body releases naturally during deep sleep. Because the pulse preserves the pituitary's own feedback control, the body does not become permanently flooded with GH — output returns to baseline within hours. Repeated dosing produces a modest, gradual rise in IGF-1, the downstream liver hormone GH is best known for.

GHRP-2 is not a GH-only signal. The same receptor (GHSR-1a) controls hunger and parts of the stress-hormone axis, so alongside the GH pulse GHRP-2 also raises ACTH and cortisol, raises prolactin, and increases appetite. In a controlled trial in seven healthy lean men, a 270-minute subcutaneous infusion of GHRP-2 (1 µg/kg/h) increased ad-libitum food intake by ~36% versus saline (Laferrère et al., JCEM 2005). The ACTH/cortisol/prolactin co-elevation profile in healthy adults was characterised head-to-head against GHRH, TRH and corticotrophin-releasing hormone (Arvat et al., Peptides 1997).

These off-target effects are the key biological difference between GHRP-2 and the more receptor-selective ipamorelin (/card/pep-00019), which produces a comparable GH pulse with much less cortisol, prolactin and appetite stimulation — and they are the main reason GHRP-2 has been displaced from most non-diagnostic community use over the past decade.

Mechanism

GHRP-2 binds the growth hormone secretagogue receptor type 1a (GHSR-1a), a G-protein-coupled receptor expressed on pituitary somatotrophs and in hypothalamic neurons. GHSR-1a was cloned in 1996 (Howard et al., Science 1996) and is the same receptor activated by the endogenous octanoylated peptide ghrelin (Kojima et al., Nature 1999). Receptor activation drives calcium influx in somatotroph cells and triggers pulsatile GH release from secretory granules; the secreted GH then stimulates hepatic IGF-1 production.

GHSR-1a signalling is not GH-specific. The receptor is widely expressed in arcuate-nucleus neurons that regulate appetite, and its activation also propagates through hypothalamic circuits that elevate corticotrophin (ACTH), and therefore cortisol, and prolactin (Arvat et al., Peptides 1997; Bowers, Comprehensive Physiology 1998). This broader signalling footprint, rather than any non-specific off-target binding, is why GHRP-2 raises cortisol and appetite alongside GH.

GHRP-2 does not suppress endogenous GHRH or ghrelin production and preserves pituitary negative feedback, which is its main pharmacological distinction from exogenous GH administration.

Evidence

• Human (diagnostic): GHRP-2 stimulation is an established pituitary provocation test. Chihara and colleagues (European Journal of Endocrinology 2007) used a 100 µg intravenous dose and defined GH cut-off values for adult GH-deficiency diagnosis (peak GH 9 µg/L for severe AGHD, 15 µg/L matching the insulin-tolerance test's 3 µg/L threshold). Subsequent published clinical literature has continued to characterise GHRP-2 as a convenient and safe alternative to insulin-tolerance testing for suspected pituitary disease (peptidelist published-research catalog, 34 PMIDs).
• Human (pharmacodynamic): The GH, ACTH, cortisol and prolactin responses in healthy adults are well-characterised (Arvat et al., Peptides 1997). The appetite-stimulating arm was confirmed in a controlled healthy-men infusion study where GHRP-2 increased food intake by ~36% versus saline (Laferrère et al., JCEM 2005).
• Therapeutic development: Phase 2 development for GH deficiency and short stature (as KP-102) was investigated through the 1990s–2000s and discontinued without market approval outside Japan (Pralmorelin review, Drugs in R&D 2004).
• Animal: Preclinical work spans rat, mouse, swine, calf and chick. It includes mechanism studies on somatotroph calcium handling, lipopolysaccharide-induced acute lung injury in rats, and a 2024 report on macrophage polarization and tendon-bone healing in a rat rotator-cuff model (peptidelist published-research catalog).
• In vitro: No dedicated in vitro receptor-pharmacology dataset is attached to this card; the mechanism is grounded in the GHSR cloning and ligand work cited above.

Known effects

• Acute GH pulse — well-characterised in human pharmacodynamic and diagnostic studies (Arvat 1997; Chihara 2007).
• IGF-1 elevation with repeat dosing — observed across the GHRP literature; magnitude depends on dose and duration.
• Appetite and food-intake increase — controlled human evidence (Laferrère 2005).
• ACTH and cortisol co-elevation — controlled human evidence (Arvat 1997); used clinically as a provocation tool in suspected Cushing's-disease workup.
• Prolactin co-elevation — controlled human evidence (Arvat 1997); modest in magnitude relative to the GH response.
• Chronic body-composition or recovery benefit — not established in controlled long-duration human trials; the case rests on the pharmacodynamic GH/IGF-1 signal rather than outcome data.

Safety signals

Factual reporting from the published literature attached to this card; this is not a personal-risk assessment.

• Cortisol and ACTH elevation is a built-in pharmacological effect of GHRP-2 at GHSR-1a (Arvat 1997). It is the basis for the peptide's use as a Cushing's-disease provocation tool and is the main reason GHRP-2 has been displaced in community use by the more selective ipamorelin.
• Prolactin elevation is similarly intrinsic (Arvat 1997). Magnitude is modest compared with TRH-induced prolactin release but is consistently measurable.
• Appetite stimulation is reliable enough to function as a primary endpoint in controlled studies (Laferrère 2005).
• Injection-site reactions, fluid retention and paraesthesia are commonly reported in the broader GH-secretagogue literature, consistent with class effects of GH/IGF-1 elevation; controlled adverse-event data specific to GHRP-2 chronic use are limited.
• Long-term safety of chronic use is not established. Human exposure data come almost entirely from acute diagnostic protocols and short pharmacodynamic studies. Chronic multi-month exposure has not been formally characterised in a controlled human trial.

Regulatory status

• Japan (PMDA): Approved October 2004 as pralmorelin (brand: GHRP Kaken, Kaken Pharmaceutical) for intravenous use as a diagnostic test for growth-hormone deficiency in adults and children over four years. This is the only formal pharmaceutical approval anywhere.
• US (FDA): Not approved for any indication. Phase 2 development for GH-deficiency indications was investigated and discontinued. Historical 503A compounding-pharmacy availability has narrowed under ongoing FDA review of peptides eligible for compounding.
• EU, UK, Canada, Australia: Not authorised as a medicine. Treated as an unapproved investigational substance; Australia's TGA classifies GH secretagogues as Schedule 4 prescription-only.
• WADA: Prohibited at all times (S2, Peptide Hormones, Growth Factors, Related Substances and Mimetics). LC-MS/MS urinary detection methods for GHRP-2 and its metabolites are validated and used routinely in WADA-accredited laboratories (Thomas et al., Drug Testing and Analysis 2010).

Myths and misconceptions

• "GHRP-2 is FDA-approved." It is not. The only approval anywhere is Japanese, as an intravenous diagnostic agent — not a therapeutic. Conflating "approved somewhere" with "approved here" is a common marketing pattern in the peptide market.
• "GHRP-2 is functionally equivalent to ipamorelin." Both activate GHSR-1a and both produce a GH pulse, but GHRP-2 also raises cortisol, prolactin and appetite at clinically relevant doses, while ipamorelin (/card/pep-00019) was specifically designed to eliminate those off-target effects (Arvat 1997 for the comparison framework).
• "GHRP-2 is undetectable in doping tests because it clears fast." Short plasma half-life does not equal undetectability. Urinary metabolites of GHRP-2 are routinely identified by LC-MS/MS in WADA-accredited laboratories.

Open questions

• Long-term safety of chronic non-diagnostic use. Most human data are from single-dose diagnostic protocols. The cumulative consequences of months of multi-daily dosing — particularly the cortisol and prolactin arm — have not been characterised in a controlled trial.
• Chronic body-composition or recovery efficacy. The "wellness" use case rests on a pharmacodynamic GH/IGF-1 signal, not on controlled outcome data; no body-composition or functional endpoint has been tested with GHRP-2 monotherapy or stack therapy in a long-duration controlled human study.
• Tendon and repair biology. A 2024 rat rotator-cuff study suggested an effect on macrophage polarization and tendon-bone healing. Whether this translates to human therapeutic use is entirely open.
• Independent replication outside the Japanese and European GHRP research programs is thin across most of the non-diagnostic claim space.

Related peptides

• Ipamorelin (/card/pep-00019) — selective GHSR-1a agonist pentapeptide; the pharmacologically "cleaner" successor that displaced GHRP-2 in most community use because it produces a comparable GH pulse with much less cortisol, prolactin and appetite stimulation.
• GHRP-6 (/card/pep-10761) — the first-generation GHRP from the same Bowers/Momany research line; stronger appetite stimulation than GHRP-2.
• Sermorelin (/card/pep-04431) — GHRH(1-29) analog; acts at the GHRH receptor rather than GHSR. Commonly paired with a GHRP-class compound on the rationale that the two pathways together produce a larger combined GH pulse than either alone.
• CJC-1295 without DAC (Modified GRF 1-29) (/card/pep-10898) and CJC-1295 with DAC (/card/pep-10826) — longer-acting GHRH analogs used in the same GHRH-plus-GHRP stacking rationale.
• Tesamorelin (/card/pep-04441) — clinically-approved GHRH analog (HIV-associated lipodystrophy); same pathway as sermorelin and the CJC-1295 analogs, with a defined therapeutic indication.
• Ghrelin (/card/pep-10760) — the endogenous octanoylated peptide whose receptor GHRP-2 was discovered to activate; the natural ligand of GHSR-1a.