GHRP-1

What is GHRP-1?

GHRP-1 (Ala-His-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2, also designated KP 101) is a synthetic growth hormone-releasing heptapeptide from the research program of Cyril Y. Bowers at Tulane University and Frank A. Momany, who together developed the GHRP class by systematically optimizing the structure of Met-enkephalin. The most important thing to understand about GHRP-1 is that its number is misleading. It is not the first GHRP. The prototype of the class was the hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, first reported by Bowers, Momany, Reynolds and Hong in Endocrinology in 1984 (PMID 6714155) and later renamed GHRP-6. GHRP-1 came afterwards: the literature that introduces it calls it a second-generation compound, with Akman and colleagues titling their 1993 Endocrinology paper 'Mechanisms of action of a second generation growth hormone-releasing peptide' (PMID 8095015), and Wu and colleagues in 1994 describing it as 'a newly synthesized GHRP (GHRP-1 or KP 101)' explicitly compared against 'the original growth hormone-releasing peptide (GHRP-6)' (PMID 8049717). GHRP-1 is an early-1990s analog of GHRP-6, not its ancestor. The program's own starting point is often misdated too. The commonly repeated 1981 Endocrinology paper (PMID 6109621) is real and is a genuine milestone in the series, but it describes neither GHRP-1 nor GHRP-6 — its most active compound was the pentapeptide Tyr-D-Trp-Ala-Trp-D-Phe-NH2. And the Met-enkephalin observation that launched the whole effort cannot predate Met-enkephalin's own discovery in late 1975. GHRP-1 releases growth hormone through what was later identified as the ghrelin receptor GHSR1a, cloned as an orphan receptor by Howard, Feighner, Cully and colleagues at Merck in 1996 (Science, PMID 8688086); its endogenous ligand ghrelin was identified three years later by Kojima, Kangawa and colleagues (Nature 1999, PMID 10604470). GHRP-1 itself was tested clinically just once in any depth — an intravenous bolus study in children and adolescents (Laron 1993, PMID 8279223) — and characterized for an unusual thyroid effect (Kraiem 1995, PMID 7627332). It was quickly passed over for GHRP-2, hexarelin, ipamorelin and the orally active MK-677 (ibutamoren). It has no current therapeutic role and is rarely stocked even in research-chemical channels; today it survives mainly in anti-doping analytical chemistry.

What GHRP-1 Is Investigated For

GHRP-1 is a pharmacology-reference topic rather than a contemporary research or consumer peptide, and the single most common claim about it — that it was the first GHRP — is wrong. The prototype of the class was the hexapeptide that became GHRP-6, reported by Bowers, Momany, Reynolds and Hong in Endocrinology in 1984 (PMID 6714155). GHRP-1 is a later analog: the papers that introduce it call it 'a second generation growth hormone-releasing peptide' (Akman et al., Endocrinology 1993, PMID 8095015) and 'a newly synthesized GHRP (GHRP-1 or KP 101)' compared against 'the original growth hormone-releasing peptide (GHRP-6)' (Wu et al., J Neuroendocrinol 1994, PMID 8049717). The numbering reflects a naming scheme, not the order of discovery. Human experience with GHRP-1 amounts to essentially one study. Laron and colleagues gave it as a 1 mcg/kg intravenous bolus — not intranasally — to 15 short but healthy children and adolescents plus eight juvenile patients with pituitary insufficiency (Acta Endocrinol 1993, PMID 8279223). All the healthy children responded with a progressive rise in plasma GH peaking at 15 to 30 minutes, significantly greater in pubertal than prepubertal subjects. The result that gets least often repeated is the most informative: six of the hypopituitary patients had no response to either GHRP-1 or GHRH. The study also recorded a significant rise in free thyroxine and a fall in TSH, which is in-vivo corroboration of the one genuinely distinctive thing about this molecule. That distinctive finding is Kraiem's (Carmel Medical Center, Haifa; Eur J Endocrinol 1995, PMID 7627332): GHRP-1, but not GHRH, inhibited TSH-stimulated thyroid hormone secretion and cAMP formation in cultured human thyroid follicles, dose-dependently. Note that Bowers and Laron are co-authors, so this is not independent of the GHRP-1 program. The class's lasting scientific legacy is real but belongs to the GHRPs collectively, not to GHRP-1: the synthetic GHRPs were the molecular bait that led Howard and colleagues at Merck to clone the orphan receptor GHS-R in 1996 (Science, PMID 8688086), and Kojima, Kangawa and colleagues to identify its endogenous ligand ghrelin in 1999 (Nature, PMID 10604470) — receptor first, hormone second. GHRP-1 itself has no FDA approval, no clinical use, and almost no vendor presence. It does, however, persist in one modern niche the page previously ignored: anti-doping analytical chemistry, where its urinary metabolites have been characterized (PMID 25869809) and it is named by name on the WADA Prohibited List.

History & Discovery

GHRP-1 belongs to the synthetic growth hormone-releasing peptide series built by Cyril Y. Bowers at Tulane University School of Medicine and Frank A. Momany, but its place in that series is almost universally misreported, so it is worth setting out in order. The work began from an anomaly. Bowers observed that Met-enkephalin and its synthetic analogs stimulated growth hormone release from pituitary cells — an effect classical opioid pharmacology did not predict, and one that pointed to a separate, non-opioid activity embedded in the enkephalin scaffold. Met-enkephalin itself was only identified in December 1975, by Hughes, Smith and Kosterlitz (Nature, PMID 1207728), so the GHRP program necessarily starts after that date rather than in the early 1970s. Bowers and Momany then ran iterative cycles of conformational modeling, synthesis and bioassay to amplify GH-releasing potency while stripping away opioid binding. The 1981 Endocrinology paper (PMID 6109621) documents that campaign, and it is a genuine landmark — but its most active compound was the pentapeptide Tyr-D-Trp-Ala-Trp-D-Phe-NH2, roughly a thousand-fold more active than the enkephalin analogs they started from. It describes neither GHRP-6 nor GHRP-1. The prototype of the class arrived three years later. Bowers, Momany, Reynolds and Hong reported the hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in Endocrinology in 1984 (PMID 6714155), describing a compound that released GH in a dose-related way without concomitant LH, FSH, TSH or prolactin release, active from 1 to 10 ng/ml in vitro, active across rats, monkeys, lambs and calves, and active intravenously, subcutaneously or intraperitoneally. That molecule became GHRP-6. GHRP-1 (Ala-His-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2, also designated KP 101) came after it, in the early 1990s. The papers introducing it say so plainly: Akman and colleagues titled their 1993 Endocrinology study 'Mechanisms of action of a second generation growth hormone-releasing peptide' (PMID 8095015), and Wu and colleagues in 1994 described 'a newly synthesized GHRP (GHRP-1 or KP 101)' explicitly benchmarked against 'the original growth hormone-releasing peptide (GHRP-6)' (PMID 8049717). Whatever the numbering suggests, GHRP-1 is a second-generation analog of GHRP-6, not its predecessor. Clinical interest was brief. Laron and colleagues gave GHRP-1 as a 1 mcg/kg intravenous bolus to 15 short but healthy children and adolescents and eight juvenile patients with pituitary insufficiency (Acta Endocrinol Copenh 1993, PMID 8279223). All the healthy children responded with a progressive GH rise peaking at 15 to 30 minutes, greater in pubertal than prepubertal subjects; six of the hypopituitary patients responded to neither GHRP-1 nor GHRH, and the study also recorded rising free thyroxine and falling TSH. Kraiem and colleagues at Carmel Medical Center in Haifa then found that GHRP-1, unlike GHRH, dose-dependently inhibited TSH-stimulated thyroid hormone secretion and cAMP formation in cultured human thyroid follicles (Eur J Endocrinol 1995, PMID 7627332) — the one pharmacological property that still distinguishes this molecule, and consistent with what Laron had seen in vivo. The class's larger legacy is not GHRP-1's to claim, though GHRP-1 was part of it. The synthetic GHRPs were the molecular bait that let Howard, Feighner and colleagues at Merck Research Laboratories clone the orphan growth hormone secretagogue receptor in 1996 (Science, PMID 8688086). Three years later Kojima, Hosoda, Date, Nakazato, Matsuo and Kangawa identified its endogenous ligand (Nature 1999, PMID 10604470): ghrelin, a 28-amino-acid peptide from gastric X/A-like cells carrying an unusual octanoyl modification on serine-3. Receptor first, hormone second — a sequence worth getting right, since a receptor cannot be identified as the ghrelin receptor before ghrelin is known to exist. The ghrelin system went on to reshape the physiology of appetite, gastric motility, glucose metabolism and GH regulation. GHRP-1 itself was passed over quickly. GHRP-2 became the workhorse research secretagogue and reached a Japanese diagnostic approval; GHRP-6 acquired the most research-channel presence; hexarelin offered greater potency; ipamorelin offered selectivity for GH over ACTH and cortisol in the original swine studies; and MK-677 (ibutamoren), developed at Merck after the receptor was cloned, offered oral activity. GHRP-1 has no approval anywhere and almost no vendor presence. Its one continuing modern thread is analytical: anti-doping laboratories have characterized its urinary metabolites (PMID 25869809), mapped its receptor structure-activity relationship alongside the rest of the class (PMID 26811125), included it in routine multi-peptide urine screens (PMID 26578461), and used its scaffold to build fluorine-18 PET probes for imaging the ghrelin receptor (PMID 30282322).

How It Works

GHRP-1 is a synthetic growth hormone-boosting peptide from the research program of Cyril Bowers at Tulane and Frank Momany, who started with Met-enkephalin (a small natural opioid peptide) and reshaped it until it strongly stimulated growth hormone release with little opioid activity. Despite the number 1, it is not the first of its family — it was made in the early 1990s, after the prototype that became GHRP-6, and the papers introducing it call it a second-generation compound. GHRP-1 works by binding the ghrelin receptor (GHSR1a) on pituitary cells, which then release growth hormone. The GHRP family as a whole led scientists to the ghrelin receptor in 1996 and then to ghrelin itself in 1999 — one of the most consequential hormone discoveries of the past thirty years. GHRP-1 was outclassed by its siblings and is mostly a reference point today.

GHRP-1 (Ala-His-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2) is a synthetic heptapeptide structurally derived from systematic optimization of Met-enkephalin. Bowers and Momany's design strategy was driven by the observation that Met-enkephalin and its analogs produced GH-releasing activity in pituitary cell cultures — an observation that cannot predate Met-enkephalin's own identification in late 1975 — and the optimization aim was to enhance GH-releasing potency while reducing opioid receptor binding. The 1981 Endocrinology paper (PMID 6109621) captures the series mid-flight, with the pentapeptide Tyr-D-Trp-Ala-Trp-D-Phe-NH2 as its most active compound. The prototype hexapeptide GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) followed in 1984 (PMID 6714155), and GHRP-1 after that, described on arrival as a second-generation analog (PMID 8095015). The wider family includes GHRP-2 (D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2), which became the most-used research GH secretagogue, and hexarelin (His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2). All share a small (6-7 residue) peptide backbone with C-terminal lysinamide and the central Trp-D-Phe pharmacophore that drives ghrelin-receptor binding. GHRP-1 acts at the growth hormone secretagogue receptor (GHSR1a, also known as the ghrelin receptor), a class A G-protein-coupled receptor encoded by the GHSR gene on human chromosome 3q26.31. GHSR1a was cloned and characterized as an orphan receptor in 1996 by Howard, Feighner, and colleagues at Merck Research Laboratories (Science, PMID 8688086), identified specifically by its responsiveness to the synthetic GHRP class — the GHRPs were the molecular bait that led to receptor identification. The endogenous ligand of GHSR1a was identified three years later in 1999 by Kojima, Kangawa, Hosoda, and Matsuo at the National Cardiovascular Center in Osaka (Nature, PMID 10604470) as ghrelin, a 28-amino-acid peptide produced by gastric X/A-like cells with a unique octanoyl modification on serine-3. The receptor couples primarily to Gq/11 with phospholipase C activation and intracellular calcium mobilization, and to Gs/cAMP secondarily, producing growth hormone release in pituitary somatotrophs. GHRP-1 (like other GHRPs) drives this signaling and produces dose-dependent GH release in vivo. The pharmacology of GHRP-1 includes the standard GH secretagogue effects: pituitary GH release with downstream IGF-1 elevation, modest cortisol and prolactin elevations through pituitary GHSR1a expression, and central effects on appetite and gastric motility through hypothalamic and brainstem GHSR1a. Kraiem's 1995 Eur J Endocrinol paper (PMID 7627332) identified an unusual additional pharmacology specific to GHRP-1: dose-dependent inhibition of TSH-stimulated thyroid hormone secretion and cAMP formation in cultured human thyroid follicles, an effect GHRH did not produce at concentrations up to 1200 mcg/l. The authors placed the action downstream of cAMP formation without excluding an additional pre-cAMP site; whether it is GHSR1a-mediated was not established, and describing it as receptor-independent goes beyond what the paper shows. Laron's in-vivo observation of rising free thyroxine and falling TSH after intravenous GHRP-1 (PMID 8279223) is consistent with a real thyroid effect. It has not been characterized in modern research. Note that Bowers and Laron are co-authors on the Kraiem paper, so these are findings from within the GHRP-1 program rather than independent replication. The only human administration of GHRP-1 described in any detail was intravenous: a 1 mcg/kg bolus in children and adolescents (Laron 1993, PMID 8279223), producing a progressive GH rise that peaked at 15 to 30 minutes. The frequently repeated claim that GHRP-1's historical route was intranasal appears to conflate two separate things — the 1991 Japanese intranasal study (PMID 1915110) administered GHRP-6, not GHRP-1, and Laron's own intranasal work was with hexarelin. The one genuine intranasal GHRP-1 human exposure in the literature is far more recent: a 2015 anti-doping study that characterized six urinary metabolites after nasal administration, with the parent peptide undetectable and the GHRP-1 (2-4) free acid measurable out to 27 hours (PMID 25869809). The broader class has been developed across routes — subcutaneous and IV for GHRP-2 and hexarelin, oral for MK-677/ibutamoren. GHRP-1 is now of mainly historical interest. Its place in the timeline matters as part of the foundational pharmacology that led to the ghrelin receptor and ghrelin itself, but its potency is lower than GHRP-2 and hexarelin, its receptor selectivity is similar to other GHRPs (no special advantage over ipamorelin's GH-selective profile), and it does not have an oral formulation comparable to MK-677. Modern GH secretagogue research and clinical interest is focused on the validated and currently-available molecules.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about GHRP-1:

• 01Whether GHRP-1's distinctive thyroid pharmacology (inhibition of TSH-stimulated thyroid hormone secretion, identified by Kraiem 1995) is mechanistically discrete from other GHRP class members and clinically meaningful — not characterized in modern research.
• 02Whether GHRP-1 has any specific advantage over the better-characterized members of the GHRP series (GHRP-2, ipamorelin, hexarelin, MK-677) — the lack of a clear advantage is the principal reason GHRP-1 was not advanced into clinical development.
• 03What the long-term safety profile of any GHRP-class agent (including GHRP-1) is in chronic dosing — modern long-term safety data for the class is limited even for the more-studied members (MK-677, ipamorelin). For GHRP-1 specifically there is no repeat-dose human exposure data at all: the entire human record is single-dose.
• 04Whether GHRP-1's thyroid effect is a class property or specific to this molecule has never been tested head-to-head. Kraiem 1995 showed GHRP-1 but not GHRH inhibits TSH-stimulated thyroid hormone secretion, and Laron 1993 saw free thyroxine rise and TSH fall in vivo, but no study has run GHRP-1 against GHRP-2, GHRP-6 or hexarelin on the same thyroid endpoint.
• 05Whether the GH secretagogue class will eventually find a clinical indication beyond the few niche uses (cachexia, post-operative ileus, diagnostic GH stimulation testing) where it has been characterized, given the dominance of recombinant GH (somatropin) and GHRH analogs (sermorelin, tesamorelin) in current clinical practice.

Forms & Administration

GHRP-1 is not formulated or approved as a therapeutic in any jurisdiction. The only substantive human study used a single 1 mcg/kg intravenous bolus (Laron 1993); an intranasal route has been used in human anti-doping metabolism work (PMID 25869809) but never in a therapeutic study. There is no current FDA-approved pen, vial, or formulation, and the molecule is not commonly available even in research-chemical peptide vendor catalogs that stock GHRP-2, GHRP-6, hexarelin, and ipamorelin. Anyone seeking growth hormone secretagogue therapy should engage with currently-available options under medical supervision: GHRH analogs (sermorelin, tesamorelin) for medical indications, the ghrelin receptor agonists ipamorelin (research-channel) or MK-677/ibutamoren (research-channel small molecule), or recombinant human growth hormone (somatropin) for medically-validated indications.

Common Questions

Who GHRP-1 Is NOT For

Drug & Supplement Interactions

There is no validated human drug-interaction profile for GHRP-1 because no clinical product is in current use. Theoretical interactions extrapolate from the GH secretagogue class. Concurrent use with other GH secretagogues (GHRP-2, GHRP-6, hexarelin, ipamorelin, MK-677), GHRH analogs (sermorelin, tesamorelin), or somatropin would produce additive GH and IGF-1 elevations with theoretical concerns about insulin resistance, fluid retention, and edema. Concurrent use with corticosteroids would compound cortisol elevation and could exacerbate hypercortisolism. Concurrent use with insulin or insulin secretagogues in diabetic patients could worsen insulin resistance. The unusual thyroid pharmacology identified by Kraiem 1995 (inhibition of TSH-stimulated thyroid hormone secretion) raises a theoretical concern in patients on thyroid hormone replacement, though the clinical relevance is unknown. None of these interactions has been characterized in controlled human studies for GHRP-1.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions