GHRP-6
Growth Hormone-Releasing Peptide-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2)
GHRP-6 is a synthetic hexapeptide ghrelin mimetic that stimulates pulsatile GH release via the GHS-R1a receptor, with multiple small human endocrine studies (Borges et al. 1997, PMID 9274702; Popovic et al. 2000, PMID 11030292; Oliveira et al. 2003, PMID 12809173) and extensive preclinical cytoprotection data, but no FDA-approved therapeutic indication.
Last updated: 2026-03-10
Safety Summary
The side-effect picture is led by appetite stimulation and endocrine spillover rather than serious toxicity. A 12-participant dose-escalation study reported 23 adverse events (6 different event types) with no serious adverse events. Other human summaries reported hunger, heat sensation, nausea, transient facial flushing, and sleepiness. FDA's 503B compounding-risk discussion specifically cites potential cortisol effects and increased blood glucose due to decreased insulin sensitivity. In the 25-person Borges study, no acute changes in IGF-I or glucose were observed in controls (PMID 9274702). GHRP-6 is considered the most appetite-stimulating peptide in the GHRP family due to strong ghrelin receptor agonism, distinguishing it from GHRP-2 and ipamorelin. Cortisol and prolactin elevations are generally described as transient (PMC5632578). In diabetic rat models, GHRP-6 combined with insulin potentiated weight gain and visceral fat accumulation.
Known Side Effects
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regulatory concern
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regulatory concern
Who Should NOT Use This
FDA's 503B risk summary specifically cites possible increased blood glucose due to decreased insulin sensitivity. In diabetic rat models, GHRP-6 combined with insulin potentiated weight gain and visceral fat accumulation.
GHRP-6 significantly increased ACTH (from 15.5 to 45.1 pmol/L) and cortisol (from 583.0 to 1013.4 nmol/L) in 10 patients with Cushing's disease (PMID 12809173). Use may exacerbate existing HPA-axis dysfunction.
Standard precaution for all GH secretagogues. GH and IGF-1 elevation may theoretically promote tumor growth. No GHRP-6-specific oncology data in source set but standard pharmacological caution applies.
Talk to Your Doctor
Before considering GHRP-6, 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: [1-11]
Evidence Assessment
Tier 3. The source set contains multiple human studies totaling approximately 300 subjects: a 25-person endocrine challenge study in hypercortisolism and controls (PMID 9274702, Borges et al.). a 10-patient Cushing's disease ACTH/cortisol study (PMID 12809173, Oliveira et al.). a 250-participant multicenter diagnostic study published in The Lancet establishing GHRH+GHRP-6 as a GH deficiency test (PMID 11030292, Popovic et al.). and a 12-volunteer dose-escalation safety study with pharmacokinetic characterization. However, the strongest human evidence is physiological or diagnostic rather than therapeutic. No Phase 2 therapeutic efficacy trials, Phase 3 RCTs, or FDA-approved indications exist. ClinicalTrials.gov searches returned no matching studies. The preclinical evidence base is extensive with multiple animal models across organ systems.
1GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adultsPMID 11030292
Popovic V, Leal A, Micic D, Koppeschaar HPF, Torres E, Paramo C, Obradovic S, Dieguez C, Casanueva FF - The Lancet (2000) - Human multicenter diagnostic study - 250 adults (125 with pituitary disease, 125 healthy controls)
GHRH+GHRP-6 test produced no side effects and was not affected by age, sex, or adiposity. Mean GH peak was 59.2 mcg/L for controls and 4.1 mcg/L for GH-deficient patients. A cutoff of 15.0 mcg/L accurately distinguished healthy from GH-deficient adults. The test was proposed as a convenient, safe, and reliable alternative to the insulin tolerance test.
Limitations: Diagnostic test validation study, not a therapeutic efficacy trial. Uses the combination of GHRH+GHRP-6, not GHRP-6 alone.
2Different effects of growth hormone releasing peptide (GHRP-6) and GH-releasing hormone on GH release in endogenous and exogenous hypercortisolismPMID 9274702
Borges MH, DiNinno FB, Lengyel AM - Clinical Endocrinology (1997) - Human endocrine challenge study - 25 adults (6 endogenous hypercortisolism, 9 exogenous glucocorticoid excess, 10 healthy controls)
GHRP-6 preserved GH responses in exogenous hypercortisolism where GHRH responses were blunted. Combined GHRH+GHRP-6 produced peak GH of 77.4 mcg/L in controls vs 24.9 mcg/L for GHRH alone. No changes in plasma IGF-I and glucose were observed. GHRP-6 and GHRH stimulate GH release by different mechanisms.
Limitations: Small physiological challenge study; acute endocrine endpoints only; not a therapeutic trial.
3GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's disease: comparison with DDAVPPMID 12809173
Oliveira JHA, Vieira JGH, Abucham J, Lengyel AMJ - Journal of Endocrinological Investigation (2003) - Human endocrine challenge study - 10 patients with active Cushing's disease (8 female, 2 male)
GHRP-6 (2 mcg/kg IV) significantly increased ACTH from 15.5 to 45.1 pmol/L and cortisol from 583.0 to 1013.4 nmol/L. Responses were similar to DDAVP. Positive correlation between peak cortisol after GHRP-6 and DDAVP (r=0.87, p=0.001). Suggests both peptides may act by similar mechanisms at hypothalamic or pituitary level.
Limitations: Disease-specific endocrine provocation study; very small sample; does not establish therapeutic benefit.
4Growth Hormone Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the WoundsPMID 27200188
Berlanga-Acosta J et al. - BioMed Research International (2016) - Animal wound-healing study - Rat full-thickness wound model (10 rats per group, two experiments) plus rabbit ear hypertrophic scar model (four experiments)
Topical GHRP-6 (400 mcg/mL CMC gel) significantly accelerated rat wound closure, reduced inflammatory cell infiltration, and downregulated profibrogenic cytokines (TGF-beta1, PDGF-B, CTGF). In rabbits, GHRP-6 prevented hypertrophic scar formation in 90.5% of treated wounds via PPARgamma upregulation. No interference with wound angiogenesis.
Limitations: Animal-only study from CIGB (developer group). Topical formulation-specific. GHRP-6 did not revert consolidated hypertrophic scars.
5Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failure
Cibrian D, Berlanga J, Guevara L et al. - Clinical Science (2006) - Animal ischemia-reperfusion study - Rats (n=6-12 per group depending on protocol) plus IEC-6 and HT29 cell experiments
Prophylactic GHRP-6 (400 mcg/kg IP, 1 hour before ischemia) reduced biochemical and histological injury in liver, lung, intestine, and kidney by approximately 50-85%. Combined GHRP-6 plus EGF produced additive protection.
Limitations: Prophylactic animal model with short follow-up. Developer-associated authorship (CIGB). Not directly translatable to chronic human use.
6Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms
Berlanga-Acosta J et al. - Frontiers in Pharmacology (2024) - Animal cardiotoxicity study - 36 male Wistar rats (12 per group)
GHRP-6 (400 mcg/kg IP, twice daily, 52 days) preserved left ventricular function, reduced morbidity and mortality, protected kidney, lung, liver, and intestinal tissues, improved redox balance, and shifted myocardial Bcl-2/Bax toward survival during doxorubicin cardiotoxicity.
Limitations: Animal-only. Developer-associated authorship (CIGB). Prophylactic design during chemotherapy rather than rescue treatment.
7Growth hormone-releasing peptide 6 (GHRP-6) hydrogel for acute kidney injury therapy via metabolic regulationPMID 41327290
Zhao X et al. - Journal of Nanobiotechnology (2025) - Animal plus in vitro formulation study - C57BL/6 mice (n=3-10 depending on endpoint) plus HK-2 and primary TEC experiments
Self-assembling GHRP-6 hydrogel delivered via intrarenal injection reduced tubular necrosis, serum creatinine, BUN, Kim-1, and later fibrosis markers. Metabolomics linked benefit to higher spermidine, L-glutamine, and acetyl-CoA plus mTOR/P70 activation in TECs.
Limitations: Formulation-specific mouse study with invasive intrarenal delivery route. Authors acknowledge translation limits. Chinese research group (not CIGB).
8Growth hormone releasing peptide-6 (GHRP-6) ameliorates acute lung injury and its subsequent evolvement to interstitial fibrosisPMID 41534456
Wang L, Berlanga-Acosta J, Yu H, Garcia-Ojalvo A, Jiang T, Li N, Zhang Z, Guillen-Nieto G, Jiang B - International Immunopharmacology (2026) - Animal lung-injury study - C57BL/6 mice (LPS and ZYM/PAF models)
GHRP-6 subcutaneous administration reduced neutrophilic alveolitis, improved lung compliance and alveolar-capillary permeability, lowered IL-1beta serum levels in acute models, and preserved lung parenchyma with meager collagen accumulation in 28-day chronic follow-up.
Limitations: Animal-only. Joint CIGB (Cuba) and Shanghai Institute of Materia Medica (Chinese Academy of Sciences) authorship. January 2026, no independent replication.
9Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective EffectsPMID 28469491
Berlanga-Acosta J, Abreu-Cruz A, Herrera DGB, Mendoza-Mari Y, Rodriguez-Ulloa A, Garcia-Ojalvo A, Falcon-Cama V, Hernandez-Bernal F, Beichen Q, Guillen-Nieto G - Clinical Medicine Insights: Cardiology (2017) - Review - Review of preclinical and clinical literature on GHRP family
Comprehensive review of GHRP pharmacology including GHS-R1a and CD36 receptor binding, cardioprotective and cytoprotective effects across organ systems. Describes broad safety profile of GHRPs but notes erratic clinical development. Reviews cardiac ischemia-reperfusion protection, multi-organ failure prevention, and anti-fibrotic properties.
Limitations: Review from the primary GHRP research group (CIGB, Cuba). Many primary studies reviewed are from the same group.
10Growth hormone-releasing peptide 6 dose-dependently stimulates food intake and hypothalamic c-fos expression in micePMID 26915318
Not established (Chinese-language paper, English abstract) - Not established (2016) - Animal appetite study - NMRI mice
GHRP-6 (1, 10, or 100 nmol IP) increased food intake in a dose-dependent manner and induced c-fos activation in arcuate, paraventricular, dorsomedial, and ventromedial hypothalamic nuclei. C-fos peaked at approximately 1 hour and food intake peaked around 3 hours.
Limitations: Animal-only Chinese-language paper represented by English abstract. No direct human appetite quantification.
11Growth Hormone-Releasing Peptides: Investigation of Their Secondary Structure, Thermal Stability, and Model Membrane Interactions
Kralik F et al. - Chirality (2026) - In vitro / structural chemistry - 8 GHRPs analyzed
Systematic ECD analysis confirmed GHRP-6 sequence as His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 with MW 873.0 Da. Characterized secondary structure and membrane interactions. References WADA 2025 Prohibited List for GHRP classification.
Limitations: Structural chemistry study providing analytical characterization rather than pharmacological data.