GHRP-2
Growth Hormone Releasing Peptide-2 (Pralmorelin; D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2)
Synthetic hexapeptide ghrelin receptor (GHS-R1a) agonist that potently stimulates GH release, approved in Japan as a diagnostic agent for GH deficiency (PMID 17609397), and studied for appetite stimulation in cachexia and anorexia nervosa (PMID 26401470, PMID 19009643, PMID 15699539).
Last updated: 2026-03-10
Safety Summary
The most reproducible effect in human studies is increased appetite/food intake: all 7 healthy men ate significantly more during GHRP-2 infusion (35.9% increase, P=0.004; PMID 15699539), and 7 of 10 GH-deficient children reported increased appetite during oral treatment (PMID 14513874). Formal adverse-event reporting in clinical studies was favorable: no side effects reported in the 7-subject feeding study (PMID 15699539), intranasal therapy described as well tolerated in pediatric study (PMID 9390009), and no obvious side effects in the 1-year anorexia nervosa case (PMID 26401470). A 30-day continuous SC infusion and 12-month oral administration in children also reported no adverse effects (as referenced in PMID 15699539). GHRPs as a class mildly stimulate cortisol and prolactin, with effects described as modest and transient (PMID 9186261). The FDA Category 2 listing cites reports of serious adverse events including increased insulin requirement, death of critically ill study subjects, infection, and pancreatitis -- though causality was not established (FDA Category 2 list). GH secretagogues as a class raise concern for decreased insulin sensitivity (PMID 28400207). Regulatory analysts cite cortisol and prolactin elevation as concerns for continued Category 2 classification (Tavily: bhrcenter.com). Community reports (not peer-reviewed) include: elevated resting heart rate (~100 BPM post-injection), significant hunger within 30 minutes, water retention, sleep disruption during initial weeks, and skin improvements. Users note GHRP-2 produces less appetite stimulation than GHRP-6 but more than ipamorelin. Long-term safety data in humans are limited (Tavily: online communities.com, mypeptidematch.com, kilobio.com).
Known Side Effects
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Who Should NOT Use This
GH and IGF-1 elevation may promote tumor progression. GH/IGF-1 axis has documented roles in cancer biology (PMID 19589948, PMID 18436706). GHRP-2 stimulates GH release from acromegalic tumor cells in vitro (PMID 9688350).
FDA Category 2 listing notes increased insulin requirement in patients receiving GHRP-2 (FDA Category 2 list). GH secretagogues as a class may decrease insulin sensitivity (PMID 28400207).
FDA Category 2 listing notes deaths among critically ill study subjects receiving GHRP-2, though causality not established (FDA Category 2 list).
GHRP-2 stimulates GH release from acromegalic tumor cells in vitro -- all 7 tumors responded (PMID 9688350). GHRPs maintain GH-releasing effect in somatotrope hypersecretory states (PMID 9186261).
Talk to Your Doctor
Before considering GHRP-2, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-23]
Evidence Assessment
Tier 3. GHRP-2 has been studied in multiple small human studies across different indications: diagnostic GHD testing in adults (N=135 across two studies; PMID 17609397, PMID 23079545), a randomized crossover feeding study in healthy men (N=7; PMID 15699539), oral administration in GH-deficient children (N=10, 12 months; PMID 14513874), intranasal in short-stature children (N=15, up to 24 months; PMID 9390009), estradiol interaction in postmenopausal women (N=24 RCT; PMID 24114435), and a single-patient anorexia nervosa case (PMID 26401470). While approved in Japan as a diagnostic agent, there are no large Phase 3 RCTs for therapeutic indications. No current ClinicalTrials.gov registrations were found in the collected source data. The evidence base consists of Phase 2-equivalent or smaller human studies.
1On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone.PMID 6714155
Bowers CY et al. - Endocrinology (1984) - animal study/in vitro - Multiple animal species (rats, monkeys, lambs, calves, chicks)
First description of the GHRP class. The synthetic hexapeptide specifically released GH in a dose-related manner without concomitant release of LH, FSH, TSH, or PRL. Active across multiple species and routes. GH levels rose within 2 min of IV injection, peaked at 10-20 min. Chronic SC administration increased body weight gain in immature rats without desensitization.
Limitations: Describes the GHRP-6 precursor peptide, not GHRP-2 specifically. Animal data only.
2Mechanisms of action of a second generation growth hormone-releasing peptide (Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2) in rat anterior pituitary cells.PMID 8095015
Akman MS et al. - Endocrinology (1993) - in vitro - Rat pituitary cell cultures
GHRP-1 (structurally related to GHRP-2) releases GH via a Ca2+-dependent, cAMP-independent mechanism, distinct from GHRH. Effects inhibited by somatostatin and nifedipine. GHRP-1-stimulated GH release was additive with cAMP-elevating agents and PKC activators, confirming a separate signaling pathway.
Limitations: Studies GHRP-1 specifically, not GHRP-2, though the mechanism is considered representative of the GHRP class. In vitro rat pituitary cells only.
3Growth hormone-releasing peptides.PMID 9186261
Ghigo E et al. - European Journal of Endocrinology (1997) - review - N/A (comprehensive review)
GHRPs act via specific receptors distinct from GHRH-R. GH-releasing effect is dose-related via IV, SC, intranasal, and oral routes. Partial desensitization with continuous infusion, less with intermittent. Prolonged administration increases IGF-1. Synergistic with GHRH. GHRPs mildly stimulate ACTH, cortisol, and prolactin. GHRP-2 noted as available for human studies.
Limitations: Review article summarizing existing literature as of 1997.
4Mechanisms of action of growth hormone-releasing peptide-2 in bovine pituitary cells.PMID 9331879
Roh SG et al. - Journal of Animal Science (1997) - in vitro (bovine) - Bovine anterior pituitary primary cell cultures
GHRP-2 (10^-13 to 10^-7 M) dose-dependently increased GH secretion. Additive with GRF. Inhibited by somatostatin and nifedipine. Additive with PKC activator and forskolin.
Limitations: In vitro bovine pituitary cells; species-specific differences possible.
5Treatment effects of intranasal growth hormone releasing peptide-2 in children with short stature.PMID 9390009
Pihoker C et al. - The Journal of Endocrinology (1997) - open-label clinical study - N=15 children (6 continued to 18-24 months)
Intranasal GHRP-2 (5-15 mcg/kg, 2-3x daily) increased height velocity from 3.7 +/- 0.2 cm/year to 6.1 +/- 0.3 cm/year at 6 months. No significant changes in IGF-1 or IGFBP-3. GHBP rose significantly from 439 +/- 63 to 688 +/- 48 pmol/L. Treatment well tolerated.
Limitations: Open-label, no placebo control. Small sample (N=15, only 6 long-term). Mixed GHD and idiopathic short stature.
6Effect of GHRP-2 and GHRH on the cAMP levels and GH release from cultured acromegalic tumours.PMID 9688350
Chen C et al. - Journal of Neuroendocrinology (1998) - in vitro (human tissue) - 7 human acromegalic tumors
GHRP-2 stimulated GH from all 7 tumors; GHRH from only 4 of 7. GHRP-2 acts primarily via PKC pathway; GHRH via cAMP/PKA. Confirms separate receptor/signaling mechanisms on human somatotrophs.
Limitations: In vitro using acromegalic (pathological) tissue. Small sample of 7 tumors.
7Changes in appetite and body weight in response to long-term oral administration of the ghrelin agonist GHRP-2 in growth hormone deficient children.PMID 14513874
Mericq V et al. - Journal of Pediatric Endocrinology & Metabolism (2003) - open-label clinical study - N=10 prepubertal GH-deficient children
Oral GHRP-2 (900 mcg/kg b.i.d.) for 12 months. 7/10 reported significant appetite increase during first 6 months (transient). BMI SDS showed tendency to increase but not statistically significant.
Limitations: Small sample (N=10). Open-label, no placebo control. Appetite/BMI were secondary endpoints.
8Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.PMID 15232612
Dixit VD et al. - The Journal of Clinical Investigation (2004) - in vitro/animal study - Human T lymphocytes and monocytes in vitro; murine endotoxemia model
GHS-R and ghrelin expressed in human T cells and monocytes. Ghrelin inhibits proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) via GHS-R. First report of ghrelin coupling metabolic axis to immune system.
Limitations: Uses ghrelin directly, not GHRP-2. In vitro human cells plus animal model.
9Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.PMID 15699539
Laferrere B et al. - Journal of Clinical Endocrinology and Metabolism (2005) - randomized double-blind placebo-controlled crossover - N=7 lean healthy males
SC GHRP-2 infusion (1 mcg/kg/h for 270 min) increased food intake by 35.9 +/- 10.9% vs. saline (P=0.004). GH AUC rose from 412 to 5550 mcg/L/240 min. Transient cortisol increase. No adverse side effects reported. Also references 30-day continuous SC infusion and 12-month oral administration as safe.
Limitations: Very small sample (N=7). All lean healthy males. Acute/single-session design.
10A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.PMID 17609397
Chihara K et al. - European Journal of Endocrinology (2007) - diagnostic validation study - N=135 (77 healthy + 58 GHD patients)
100 mcg IV GHRP-2 produced peak GH within 60 min. GH not affected by gender; slightly lower in elderly/adipose but not enough to influence diagnosis. Peak GH: patients 1.36 +/- 2.60 mcg/L vs. healthy 84.6 +/- 60.9 mcg/L (P<0.001). Cutoff 15 mcg/L for GHD. Favorable reproducibility.
Limitations: Single-center. Japanese population.
11Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice.PMID 19009643
Perboni S et al. - World Journal of Gastroenterology (2008) - animal study - N=33 tumor-bearing mice + 10 controls
5-FU + GHRP-2 significantly increased cumulative food intake vs. 5-FU alone at 6 hours (P=0.0096). Median survival longer with 5-FU+GHRP-2 vs. 5-FU alone (18 vs. 15.5 days, P=0.7 NS). First demonstration GHRP-2 improves appetite during cytotoxic chemotherapy in tumor-bearing mice.
Limitations: Animal model. Survival difference not significant. Small groups.
12The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: a comparison.PMID 23079545
Kinoshita Y et al. - Endocrine Journal (2013) - diagnostic comparison study - N=71 pre-operative adults with pituitary tumors
GHRP-2 test: median peak GH 28.88 mcg/L. For severe AGHD (ITT peak GH <=1.8 mcg/L): GHRP-2 sensitivity 81.3%, specificity 94.5%. ARG sensitivity 93.8%, specificity 85.5%. Both acceptable alternatives to ITT.
Limitations: Japanese population only. Pre-operative patients only.
13Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone and somatostatin in postmenopausal women.PMID 24114435
Norman C et al. - European Journal of Endocrinology (2014) - RCT (double-blind, randomized, prospective) - N=24 healthy postmenopausal women
E2 augmented mean 13-h GH concentrations (P=0.023) and GHRH-induced pulsatile GH secretion (P=0.0085). E2 concentrations positively correlated with GH secretion during GHRP-2 infusion (P=0.022). BMI negatively correlated with GH secretion during GHRH and combined GHRH/GHRP.
Limitations: Small sample (N=24). Postmenopausal women only.
14One-year intranasal application of growth hormone releasing peptide-2 improves body weight and hypoglycemia in a severely emaciated anorexia nervosa patient.PMID 26401470
Haruta I et al. - Journal of Cachexia, Sarcopenia and Muscle (2015) - case report - N=1
Intranasal GHRP-2 before every meal for 1 year. Body weight increased from 21.1 to 27.8 kg (6.7 kg gain in 14 months). Increased hunger, food intake; improved hypoglycemia, fatigability, muscle strength. No obvious side effects.
Limitations: Single case report (N=1). No control. 20-year disease history.
15Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks with Growth Retardation.
Hu R et al. - PLoS One (2016) - animal study (yaks) - N=20 yaks (5 per group)
GHRP-2 significantly increased average daily gain. Enhanced myofiber diameter and area. Increased serum GH and IGF-1. Upregulated PI3K/Akt/mTOR pathway in muscle.
Limitations: Animal study. Small sample (N=5 per group).
16Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors.PMID 9092793
McKee KK et al. - Molecular Endocrinology (1997) - molecular biology - N/A (receptor cloning/characterization)
Isolation and characterization of rat GHS-R cDNA. Expression specifically in pituitary and hypothalamus. High affinity binding. Establishes the molecular identity of the GHRP target receptor.
Limitations: Rat receptor characterization. Molecular study, not clinical.
17Ghrelin.PMID 26042199
Muller TD et al. - Molecular Metabolism (2015) - review - N/A (comprehensive review)
Major review of ghrelin biology 15 years after discovery. Ghrelin has pleiotropic central and peripheral actions: GH secretion, appetite regulation, gut motility, gastric acid secretion, sleep/wake rhythm, reward seeking, taste sensation, glucose metabolism.
Limitations: Review focused on endogenous ghrelin, not GHRP-2 specifically.
18The Safety and Efficacy of Growth Hormone Secretagogues.PMID 28400207
Sigalos JT, Pastuszak AW - Sexual Medicine Reviews (2018) - review - N/A (systematic review of GHS studies)
GHSs promote pulsatile GH release subject to negative feedback. May improve growth velocity, appetite, lean mass, sleep. Well tolerated with some concern for blood glucose increases and decreased insulin sensitivity.
Limitations: Covers GHS class broadly, not GHRP-2 specifically.
19The CD36-PPARgamma Pathway in Metabolic Disorders.PMID 29883404
Marechal L et al. - International Journal of Molecular Sciences (2018) - review - N/A
GHRPs (primarily hexarelin) activate PPARgamma through CD36 scavenger receptor. Benefits on atherosclerosis, hepatic cholesterol biosynthesis, and fat mitochondrial biogenesis.
Limitations: Primarily about hexarelin and CD36, not GHRP-2 directly.
20From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation.PMID 28134808
Howick K et al. - International Journal of Molecular Sciences (2017) - review - N/A
Reviews ghrelin receptor (GHSR-1a) as therapeutic target for appetite modulation. Discusses complexity of receptor signaling, heterodimerization, and biased ligand interactions.
Limitations: Review focused on ghrelin receptor broadly.
21Growth Hormone-Releasing Peptides: Investigation of Their Secondary Structure, Thermal Stability, and Model Membrane Interactions.
Kralik F et al. - PMC (journal not specified) (2026) - biophysical characterization - N/A (structural study of GHRP-1 through GHRP-6, Ipamorelin, Anamorelin)
Characterized UV, ECD, and VCD spectra of GHRPs including GHRP-2. Notes GHRPs on WADA 2025 Prohibited Substances List (S2.2.4). Methods for identification/quantification developed for anti-doping.
Limitations: Biophysical characterization, not clinical.
22Diagnosis and treatment of adult growth hormone deficiency (aGHD) resulting from brain injury -- role of aGHD.PMID 19110756
Arita K et al. - Brain and Nerve (Shinkei kenkyu no shinpo) (2008) - review - N/A
States GHRP-2 test cutoff of 9 ng/mL for aGHD. Notes test is currently available only in Japan. Describes it as a safe and quick method.
Limitations: Japanese-language review.
23Therapeutic Potential of Targeting the Ghrelin Pathway.PMID 28398233
Collden G et al. - International Journal of Molecular Sciences (2017) - review - N/A
Reviews therapeutic potential of ghrelin pathway for anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, inflammatory disorders, metabolic syndrome.
Limitations: Discusses ghrelin pathway broadly.