Hexarelin
Hexarelin (Examorelin)
Synthetic hexapeptide GH secretagogue that produces rapid, dose-dependent GH release via GHS-R1a activation. The most potent acute GHRP but also raises ACTH, cortisol, and prolactin. Unique among GHRPs for GH-independent cardioprotective activity via a distinct cardiac receptor (CD36), demonstrated in animal models. Human evidence limited to small endocrine physiology studies; no modern clinical outcome trials exist (PMID 7957536, PMID 9430449, PMID 11238504, PMID 12486113).
Last updated: 2026-03-10
Safety Summary
Across small human studies, hexarelin repeatedly raised ACTH, cortisol, and prolactin alongside GH stimulation (PMID 9430449, PMID 11238504, DOI 10.1007/BF03350297). In the 16-week chronic study, repeated dosing caused partial but reversible reduction in GH responsiveness without significant changes in IGF-1, lean mass, fat mass, or bone mineral density (PMID 9589671). Review material notes shorter stage 4 sleep after hexarelin (PMC5632578 via). Some users report flushing and water retention but these are not systematically documented in clinical studies.
Known Side Effects
common
common
common
uncommon
uncommon
uncommon
Who Should NOT Use This
WADA section S2 prohibits growth hormone secretagogues and specifically lists examorelin among GHRPs prohibited at all times.
GHS-R binding sites were found in human breast carcinomas, with highest binding in well-differentiated tumors (PMID 11297611). While in-vitro data showed anti-proliferative effects, the interaction between hexarelin and tumor GHS receptors warrants caution. Theoretical concern, not established by clinical data.
Hexarelin reliably elevates prolactin in human studies (PMID 11238504, DOI 10.1007/BF03350297). Caution is warranted in patients with baseline prolactin elevation, though no clinical interaction data exist.
Hexarelin acutely alters all four analytes in human studies and can confound endocrine testing (PMID 7957536, PMID 9430449, PMID 11238504).
Talk to Your Doctor
Before considering Hexarelin, 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: [1-19]
Evidence Assessment
Tier 3 is appropriate because the source set contains multiple small human studies (N=7 to N=16), but all are endocrine physiology studies rather than large therapeutic outcome trials. Human evidence includes: a 12-man IV dose-response trial (PMID 7957536), two 7-subject hormone interaction studies (PMID 9430449, PMID 11238504), a 16-week chronic-dosing study with body composition endpoints (PMID 9589671), a 16-subject comparison in anorexia nervosa versus controls (DOI 10.1007/BF03350297), and peripheral binding characterization (PMID 11061542). What is missing are modern randomized therapeutic trials, large safety datasets, and any human cardiovascular outcome data. The extensive preclinical cardiovascular literature does not elevate the tier because no human cardiac trials exist.
1Growth hormone-releasing activity of hexarelin in humans. A dose-response study.PMID 7957536
Imbimbo et al. - European Journal of Clinical Pharmacology (1994) - Double-blind placebo-controlled dose-escalation (human) - 12 healthy adult men
Single IV doses of 0.5, 1, and 2 mcg/kg increased GH dose-dependently, with Cmax values of 26.9, 52.3, and 55.0 ng/mL vs 3.9 ng/mL placebo, peaking at approximately 30 minutes. ED50 0.50-0.64 mcg/kg. Calculated half-life approximately 55 minutes.
Limitations: Healthy men only, acute IV dosing only, endocrine endpoints rather than clinical outcomes.
2Hexarelin, a synthetic growth-hormone releasing peptide, shows no interaction with corticotropin-releasing hormone and vasopressin on adrenocorticotropin and cortisol secretion in humans.PMID 9430449
Arvat et al. - Neuroendocrinology (1997) - Human endocrine interaction study - 7 healthy young volunteers
IV hexarelin 2 mcg/kg increased ACTH peak to 26.3 vs 15.8 pg/mL and cortisol peak to 145.0 vs 131.7 mcg/L. GH rose to 55.7 vs 2.7 mcg/L. No synergistic interaction with CRH or vasopressin on ACTH/cortisol, suggesting an independent ACTH-releasing mechanism.
Limitations: Very small sample, acute challenge design, biomarker outcomes only.
3Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone.PMID 11238504
Arvat et al. - The Journal of Clinical Endocrinology and Metabolism (2001) - Human crossover endocrine comparison study - 7 healthy young men; 6 also completed combination testing
Hexarelin 1 mcg/kg IV produced GH Cmax 68.4 mcg/L (AUC 1546.9 mcg/L.h), higher than GHRH but lower than ghrelin. Hexarelin also increased prolactin, ACTH, and cortisol. Ghrelin + hexarelin showed no added interaction; ghrelin + GHRH was synergistic.
Limitations: Small male-only sample, acute endocrine outcomes, limited combination arm.
4Growth hormone status during long-term hexarelin therapy.PMID 9589671
Rahim et al. - The Journal of Clinical Endocrinology and Metabolism (1998) - Prospective repeated-dose human study - Adult cohort (exact N not stated in abstract)
Twice-daily SC hexarelin at 1.5 mcg/kg for 16 weeks reduced GH AUC from 19.1 to 10.5 mcg/L.h by week 16, with recovery to 19.4 mcg/L.h after 4 weeks off drug. IGF-I, IGFBP-3, total body fat, lean mass, and bone mineral density were unchanged.
Limitations: Sample size not specified in abstract. Chronic clinical efficacy limited by desensitization.
5Hexarelin is a stronger GH-releasing peptide than GHRH in normal cycling women but not in anorexia nervosa.
Giusti et al. - Journal of Endocrinological Investigation (1997) - Human comparative physiology study - 9 women with anorexia nervosa in recovery phase + 7 normal cycling women
In controls, IV hexarelin produced higher GH peak than GHRH and caused persistent prolactin release. In women recovering from anorexia nervosa, hexarelin GH response was blunted relative to controls.
Limitations: Small mixed population, endocrine outcomes only, anorexia recovery physiology limits generalizability.
6Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat.PMID 8921832
Torsello et al. - European Journal of Endocrinology (1996) - Animal mechanistic study (rat) - Infant and adult rat models
Three non-mutually-exclusive mechanisms proposed: (1) minor direct pituitary action, (2) indirect GHRH-release-dependent action in adults, (3) action through unknown hypothalamic factor synergizing with GHRH. Hexarelin outperformed GHRH in intact adult rats.
Limitations: Rat model, mechanistic design, high experimental doses.
7Growth hormone secretagogue binding sites in peripheral human tissues.PMID 11061542
Papotti M et al. - The Journal of Clinical Endocrinology and Metabolism (2000) - Human tissue radioligand binding study - Multiple human tissue types from surgical specimens
Highest GHS binding in myocardium, followed by adrenal, gonads, arteries, lung, liver, skeletal muscle, kidney, pituitary, thyroid, adipose tissue. Novel receptor subtype, specific for peptidyl GHS, identified in heart and endocrine tissues distinct from GHS-R1a.
Limitations: In vitro binding study on excised tissue. Functional significance of peripheral binding not established in this study.
8Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.PMID 12486113
Bhatt R et al. - The Journal of Cell Biology (2003) - In vitro (primary cardiomyocytes and endothelial cells) - Primary adult and H9c2 cardiomyocytes, endothelial cells
Ghrelin, des-acyl ghrelin, and hexarelin all inhibited apoptosis in cardiomyocytes and endothelial cells via ERK1/2 and Akt activation. H9c2 cardiomyocytes did not express GHS-R1a, indicating a novel receptor (later identified as CD36). Effect independent of GH release and ghrelin acylation.
Limitations: In vitro study. Novel receptor identity confirmed in later work. Translational relevance to human cardiac disease not established.
9Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans.PMID 11600590
Broglio F et al. - The Journal of Clinical Endocrinology and Metabolism (2001) - Human endocrine comparison study - 11 normal young volunteers
Ghrelin induced prompt glucose increase, marked GH release, and decreased insulin. Hexarelin induced strong GH release (DeltaAUC 4156.8 mcg/L.h) slightly lower than ghrelin but did not modify glucose or insulin levels.
Limitations: Small sample, acute challenge, biomarker outcomes only.
10Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines.PMID 11297611
Cassoni P et al. - The Journal of Clinical Endocrinology and Metabolism (2001) - In vitro study (human breast cancer tissue and cell lines) - Multiple breast carcinoma types; MCF7, T47D, MDA-MB231 cell lines
Specific GHS binding sites found in breast carcinomas, highest in well-differentiated (G1) tumors. Hexarelin and other GHS caused significant inhibition of cell proliferation. Cells did not express GHS-R1a mRNA, indicating a novel receptor type.
Limitations: In vitro only. Novel receptor not identified. Anti-proliferative effect may not translate in vivo.
11Growth hormone in obesity.PMID 10193871
Scacchi M et al. - International Journal of Obesity (1999) - Review (with human data on hexarelin) - Review of multiple studies
GHRP-6 and hexarelin elicit greater GH responses than GHRH in obese patients, though still lower than in lean subjects. Combined GHRH+GHRP is the most powerful GH stimulus in obesity.
Limitations: Review article; hexarelin data from referenced studies, not original.
12Effects of hexarelin on retinal ganglion cell survival after optic nerve transection.PMID 41766237
Not specified in abstract - Not specified in abstract (2025) - Animal study (rat) - Rat optic nerve transection model
Hexarelin dose-dependently promoted retinal ganglion cell survival up to 109.2% of control at optimal concentration after optic nerve transection.
Limitations: Animal study only. Single disease model.
13Hexarelin targets neuroinflammatory pathways to preserve cardiac morphology and function in a mouse model of myocardial ischemia-reperfusion.
McDonald H et al. - Biomedicine and Pharmacotherapy (2020) - Animal study (mouse) - Mice with myocardial ischemia-reperfusion
Hexarelin decreased TGF-beta1 expression and myofibroblast differentiation post-MI. Works via vagal enhancement and cholinergic anti-inflammatory pathway activation.
Limitations: Animal study. Single oral dose. Translational relevance unclear.
14Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury.
Zambelli V et al. - Drug Target Insights (2021) - Animal study (mouse) - Mouse ARDS model
Hexarelin improved respiratory compliance, reduced protein levels, prevented neutrophil infiltration, attenuated fibrosis in ARDS model. Mechanism involves RAAS interference.
Limitations: Animal study only. Single disease model. No human pulmonary data.
15Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.
Guan C et al. - European Journal of Medical Research (2023) - Animal/computational study - Ischemic AKI model
Hexarelin interacted with MDM2 to inhibit p53, reducing cell death in ischemic AKI. Separate from GH pathway.
Limitations: Animal study with computational docking. Novel mechanism needs validation.
16Protective Effects of Hexarelin and JMV2894 in a Human Neuroblastoma Cell Line Expressing the SOD1-G93A Mutated Protein.
Meanti R et al. - International Journal of Molecular Sciences (2023) - In vitro study (human neuroblastoma cells) - SOD1-G93A expressing neuroblastoma cells
Hexarelin significantly decreased DNA damage markers compared to H2O2-treated cells. Protected against oxidative injury in ALS-associated mutant cells.
Limitations: In vitro only. Single-gene mutation model.
17Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats.
Baser T et al. - Canadian Journal of Physiology and Pharmacology (2021) - Animal study (rat) - Rats with morphine-induced tolerance
Co-administration of hexarelin (0.2 mg/kg) with morphine reduced morphine tolerance development and enhanced pain relief.
Limitations: Animal study. Single hexarelin dose tested.
18Identification of alexamorelin consumption biomarkers using human hepatocyte incubations and high-resolution mass spectrometry.PMID 40465419
Pobee E et al. - Journal of Analytical Toxicology (2025) - In vitro (human hepatocytes) - Pooled human hepatocytes from 10 donors
Alexamorelin is metabolized to hexarelin via C-terminal cleavage. Relevant for anti-doping: hexarelin detection is not specific to alexamorelin consumption.
Limitations: In vitro hepatocyte study. Anti-doping relevance only.
19Hexarelin promotes retinal ganglion cell survival and visual function recovery after optic nerve crush.PMID 29627764
Not specified - European Journal of Pharmacology (2018) - Animal study (rat) - Rat optic nerve crush model
Hexarelin promoted RGC survival and improved visual function recovery after optic nerve injury.
Limitations: Animal study only.