Hexarelin
Also known as: GHRP-6 analog, His-D-2-methylTrp-Ala-Trp-D-Phe-Lys-NH2, Examorelin, EP23905, MF-6003
Synthetic growth hormone-releasing peptide (GHRP); Growth hormone secretagogue (GHS); GHS receptor agonist
What it is
Hexarelin is a synthetic hexapeptide (His-D-2-methylTrp-Ala-Trp-D-Phe-Lys-NH2), a non-natural superanalog of GHRP-6, that acts as a potent agonist at growth hormone secretagogue receptors (GHS-R1a) present at both the pituitary and hypothalamic levels, as well as in peripheral tissues including heart, adrenal glands, ovary, testis, lung, and skeletal muscle. It stimulates GH release via a mechanism distinct from GHRH, likely involving counteraction of somatostatinergic activity and/or partial GHRH-mediated pathways. Hexarelin also stimulates prolactin and ACTH/cortisol secretion, and its effect on the HPA axis appears to involve stimulation of arginine vasopressin (AVP) release rather than CRH. Beyond neuroendocrine effects, hexarelin exerts GH-independent cardiovascular actions via specific cardiac GHS receptors, anti-apoptotic and cytoprotective effects in cardiomyocytes (PMID 60526442 [sic: 31526442], 54), and PPARγ-activating effects through CD36. Neuroprotective properties have been demonstrated in several in vitro and animal models (PMID 36674509, 34066741, 48766237 [sic: 41766237]).
Class: Synthetic growth hormone-releasing peptide (GHRP); Growth hormone secretagogue (GHS); GHS receptor agonist
What it's studied for
- GH secretagogue / diagnostic test for GH reserve Human observational
- Hexarelin administered i.v., s.c., intranasally, and orally produced dose-dependent GH release in healthy volunteers. Biological bioavailabilities: 77% (s.c.), 4.8% (intranasal), 0.3% (oral). GH response to 1 µg/kg i.v. hexarelin was approximately 2-fold higher than 1 µg/kg GHRH. PMID 8126144 Ghigo E et al. J Clin Endocrinol Metab. 1994
- In 19 patients with possible pituitary disease, subnormal GH response to hexarelin (2 µg/kg i.v.) predicted GH deficiency on insulin tolerance test. Authors suggest hexarelin could serve as a screening test for adult GH deficiency, particularly when ITT is contraindicated. PMID 10469018 Korbonits M et al. Clin Endocrinol. 1999
- 16 weeks of twice-daily s.c. hexarelin (1.5 µg/kg) in elderly subjects caused partial, reversible attenuation of GH response. IGF-I, IGFBP-3, body composition, and bone mineral density did not change significantly; one bone formation marker (C-terminal propeptide of type I collagen) increased. PMID 9589671 Rahim A et al. J Clin Endocrinol Metab. 1998
- In prepubertal short normal children, hexarelin (2 µg/kg i.v.) GH response had limited intraindividual variability (CV ~23%). Testosterone and ethinyl estradiol, but not oxandrolone, augmented the GH response, suggesting estrogen mediation. PMID 9062497 Loche S et al. J Clin Endocrinol Metab. 1997
- Cardiovascular protection / cardiac function improvement Mixed
- Acute hexarelin (2.0 µg/kg i.v.) in patients with coronary artery disease undergoing bypass surgery significantly increased LVEF, cardiac index, and cardiac output within 10 min, lasting up to 90 min. Effects not shared by GHRH or rhGH, indicating GH-independent cardiovascular GHS receptor activation. PMID 12144941 Broglio F et al. Eur J Pharmacol. 2002
- In a murine myocardial ischemia-reperfusion model, hexarelin (0.3 mg/kg/day for 21 days, first dose immediately prior to reperfusion) significantly improved LV function, decreased interstitial collagen and TGF-β1, and reduced cardiac troponin-I and TNF-α levels. PMID 32403043 McDonald H et al. Biomed Pharmacother. 2020
- Hexarelin (200 µg/kg twice per day) in a mouse elastase-induced abdominal aortic aneurysm model decreased aortic diameter, improved elastin preservation, rescued smooth muscle cell contractile phenotype, and inhibited NLRP3 inflammasome and NF-κB signaling. PMID 34856183 Jiang B et al. Microvasc Res. 2022
- Chronic hexarelin injection (s.c. BID, 30 days) in rats with diet/vitamin D3-induced atherosclerosis suppressed plaque formation, partially reversed HDL-c/LDL-c ratio, increased vascular NO and eNOS mRNA, decreased VSMC proliferation, and reduced foam cell formation. PMID 19931584 Pang J et al. Peptides. 2010
- In anesthetized Sprague-Dawley rats, acute hexarelin evoked coronary microvascular dilation via GHS-R1a, nitric oxide, and endothelium-derived hyperpolarization. However, chronic hexarelin prior to sugen chronic hypoxia did not prevent RV hypertrophy or RV cardiomyocyte relaxation impairment in a pulmonary hypertension PMID 35126171 Waddingham MT et al. Front Physiol. 2021
- Neuroprotection (ALS model, oxidative stress, optic nerve injury) Animal studies only
- Hexarelin (1 µM) protected human neuroblastoma SH-SY5Y SOD1-G93A cells from H2O2-induced cytotoxicity by activating molecules regulating apoptosis and promoting cell survival, suggesting potential in ALS therapy. PMID 36674509 Meanti R et al. Int J Mol Sci. 2023
- In golden hamsters following optic nerve transection, single daily doses of hexarelin (25, 50, 100 µg/kg) dose-dependently increased retinal ganglion cell survival. Two daily doses of 150 µg/kg hexarelin were optimal for RGC survival. PMID 41766237 Chow KBS. Indian J Pharmacol. 2026
- Hexarelin inhibited H2O2-induced apoptosis in Neuro-2A cells by improving cell viability, reducing NO release, downregulating caspase-3/7 and Bax mRNA, inhibiting MAPK phosphorylation, and increasing p-Akt expression. PMID 34066741 Meanti R et al. Pharmaceuticals. 2021
- Metabolic disorders / diabetes / atherosclerosis (CD36-PPARγ pathway) Animal studies only
- Review summarizing hexarelin's role as a potent inducer of PPARγ through CD36 activation, with reported benefits on atherosclerosis, hepatic cholesterol biosynthesis, and fat mitochondrial biogenesis in animal models. PMID 29883404 Maréchal L et al. Int J Mol Sci. 2018
- Review: hexarelin has been reported to regulate PPARγ in macrophages and adipocytes and may exert GH-independent cardiovascular and metabolic activities relevant to diabetes and diabetic cardiomyopathy. PMID 25045704 Mosa RMH et al. Endocrine. 2015
- Organ protection (kidney, lung, pancreas) against ischemia/reperfusion and toxic injury Animal studies only
- In I/R-induced AKI rats, hexarelin pretreatment (100 µg/kg/d for 7 days) mitigated tubular necrosis, improved renal function, and inhibited apoptosis via downregulation of Caspase-3, Bax, Bad and upregulation of Bcl-2, potentially through MDM2/p53 pathway. PMID 37710348 Guan C et al. Eur J Med Res. 2023
- In a murine HCl-induced ARDS model, hexarelin (320 µg/kg i.p.) before or after challenge improved lung compliance, reduced immune cell recruitment and neutrophils in BAL, and reduced pulmonary collagen deposition at day 14. PMID 34871336 Zambelli V et al. Drug Target Insights. 2021
- Hexarelin (10 µg/kg i.p.) administered twice (4-h intervals) before or after intranasal MPTP in mice significantly reduced pulmonary histopathological damage, Caspase-3 and IL-6 expression, and improved SOD immunoreactivity. PMID 42619489 Celikoglu O et al. J Basic Clin Physiol Pharmacol. 2026
- Hexarelin attenuated MPTP-associated pancreatic injury in BALB/c mice, reducing inflammatory markers (CD11b, CD68, IL-1β, TNF-α), apoptosis (caspase-3), and β-amyloid immunoreactivity while partially preserving islet morphology and insulin immunoreactivity. PMID 42758352 Şahin M et al. J Mol Histol. 2026
- HPA axis stimulation / diagnostic use in Cushing's disease differentiation Human observational
- Randomized single-blind study: hexarelin (2 µg/kg i.v.) induced striking ACTH/cortisol responses in Cushing's disease patients but not in alcohol-induced pseudo-Cushing's syndrome, suggesting utility in differential diagnosis. PMID 10886488 Coiro V et al. J Intern Med. 2000
- Hexarelin's stimulation of HPA axis in healthy young males appears mediated by AVP, not CRH, based on combination studies with desmopressin and CRH. PMID 10404825 Korbonits M et al. J Clin Endocrinol Metab. 1999
- Sleep modulation Human observational
- In 7 young healthy male volunteers, repetitive hexarelin (4 × 50 µg at 22:00, 23:00, 24:00, 01:00 h) decreased stage 4 slow-wave sleep and EEG delta power, and increased GH, prolactin, ACTH, and cortisol. Leptin and TNF-α were unchanged. Authors hypothesize sleep impairment is due to shift in GHRH/CRH ratio in favour o PMID 15177700 Frieboes RM et al. Psychoneuroendocrinology. 2004
- Attenuation of morphine analgesic tolerance Animal studies only
- In Wistar rats, hexarelin (0.2 mg/kg) combined with morphine attenuated analgesic tolerance to morphine and enhanced antinociception in tail-flick and hot-plate tests. PMID 32893668 Baser T et al. Can J Physiol Pharmacol. 2021
- Growth velocity improvement in short stature / GH deficiency Human observational
- Review noting that in short children, an increase in height velocity has been reported during chronic GHRP treatment; GHRPs including hexarelin have shown clinical usefulness for stimulating GH secretion in some GH hyposecretory states. PMID 9186261 Ghigo E et al. Eur J Endocrinol. 1997
- Review noting potential role of GHRPs in treatment of short stature, aging, catabolic states, and dilated cardiomyopathy. PMID 9465289 Camanni F et al. Front Neuroendocrinol. 1998
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Intravenous, subcutaneous, intranasal, oral | 1 µg/kg and 2 µg/kg i.v.; 1.5 µg/kg and 3 µg/kg s.c.; 20 µg/kg intranasal; 20 mg and 40 mg oral | Single administration | human | Research PMID 8126144 |
| Subcutaneous | 1.5 µg/kg twice daily s.c. | 16 weeks | human | Research PMID 9589671 |
| Subcutaneous | 1.5 µg/kg twice daily s.c. | 16 weeks | human | Research PMID 10341859 |
| Intravenous | 2.0 µg/kg i.v. (single acute dose) | Single administration | human | Research PMID 12144941 |
| Intravenous | 2 µg/kg i.v. | Single administration | human | Research PMID 10469018 |
| Intravenous | 2 µg/kg i.v. | Single administration | human | Research PMID 10886488 |
| Intravenous | 0–1.0 µg/kg i.v. (dose-response; 0, 0.125, 0.25, 0.5, 1.0 µg/kg) | Single administration | human | Research PMID 8954038 |
| Not specified (context implies i.v. or s.c.) | 4 × 50 µg (given at 22:00, 23:00, 24:00, and 01:00 h) | Single night | human | Research PMID 15177700 |
| Intravenous | 2 µg/kg i.v. | Single administration | human | Research PMID 9062497 |
| Intravenous | 2 µg/kg i.v. | Single administration | human | Research PMID 9814463 |
| Intravenous | 1 µg/kg i.v. | Single administration | human | Research PMID 9231048 |
| Intravenous | 1 µg/kg and 2 µg/kg i.v. | Single administration | human | Research PMID 9285939 |
| Subcutaneous | 1.5 µg/kg s.c. | Single administration | human | Research PMID 10197083 |
| Intravenous; intranasal | 1 µg/kg i.v. and 20 µg/kg intranasal | Single administration | human | Research PMID 7955465 |
| Subcutaneous | Chronic hexarelin injection s.c. BID for 30 days (exact dose per injection not stated in abstract) | 30 days | animal | Research PMID 19931584 |
| Not specified in abstract | 100 µg/kg/day for 7 days before sacrifice | 7 days pretreatment | animal | Research PMID 37710348 |
| Intraperitoneal | 320 µg/kg i.p. | Single administration (before or after HCl challenge) | animal | Research PMID 34871336 |
| Not specified in abstract | 200 µg/kg twice per day | Not specified beyond study period | animal | Research PMID 34856183 |
| Not specified in abstract | 0.3 mg/kg/day for 21 days | 21 days | animal | Research PMID 32403043 |
| Intraperitoneal | 10 µg/kg i.p. twice (4-h intervals) | Single day (two doses 4 h apart) | animal | Research PMID 42619489 |
| Not specified in abstract (injection) | 25 µg/kg, 50 µg/kg, and 100 µg/kg once daily; 100 µg/kg and 150 µg/kg twice daily for 5 days | 5 days | animal | Research PMID 41766237 |
| Not specified in abstract | 0.2 mg/kg | Not specified beyond tolerance induction period | animal | Research PMID 32893668 |
| In vitro | 1 µM | 24 hours incubation | in_vitro | Research PMID 36674509 |
| In vitro | Various concentrations (specific µM values not detailed in abstract excerpt) | 24 hours | in_vitro | Research PMID 34066741 |
| In vitro | Significant responses at 3 µM; maximal effects at ~30 µM | 12–18 hours incubation | in_vitro | Research PMID 12379504 |
| subcutaneous injection | 100 mcg | 2-3x per day | Bodybuilders and biohackers seeking GH pulse stimulation and muscle gain | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 200 mcg | 2x per day | Experienced biohackers and bodybuilders seeking stronger GH pulse | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 200 mcg | 3x per day | Advanced bodybuilders running aggressive GH-stimulating protocols | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 100 mcg | 1x per day (pre-workout) | Biohackers and fitness-focused users preferring lower-frequency, longer-cycle approach | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 100 mcg | 2x per day | Biohackers concerned about Hexarelin receptor desensitization | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 200 mcg | 2x per day | Intermediate to advanced users running Hexarelin in combination with a GHRH (e.g., CJC-1295 or Mod GRF 1-29) | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 100 mcg | 1x per day (before bed) | Anti-aging biohackers and longevity-focused users seeking overnight GH pulse | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 50 mcg | 2x per day | Beginners or users sensitive to GHRP side effects (increased appetite, cortisol, prolactin) | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 200 mcg | 2x per day | Users seeking cardioprotective or cardiac recovery benefits reported in research literature | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 100 mcg | 2x per day | Post-cycle therapy (PCT) or post-steroid-cycle users seeking endogenous GH axis restoration | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
References
- [1] PMID 8126144 — Hexarelin administered i.v., s.c., intranasally, and orally produced dose-dependent GH release in healthy volunteers. Biological bioavailabilities: 77% (s.c.),
- [2] PMID 10469018 — In 19 patients with possible pituitary disease, subnormal GH response to hexarelin (2 µg/kg i.v.) predicted GH deficiency on insulin tolerance test. Authors sug
- [3] PMID 9589671 — 16 weeks of twice-daily s.c. hexarelin (1.5 µg/kg) in elderly subjects caused partial, reversible attenuation of GH response. IGF-I, IGFBP-3, body composition,
- [4] PMID 9062497 — In prepubertal short normal children, hexarelin (2 µg/kg i.v.) GH response had limited intraindividual variability (CV ~23%). Testosterone and ethinyl estradiol
- [5] PMID 12144941 — Acute hexarelin (2.0 µg/kg i.v.) in patients with coronary artery disease undergoing bypass surgery significantly increased LVEF, cardiac index, and cardiac out
- [6] PMID 32403043 — In a murine myocardial ischemia-reperfusion model, hexarelin (0.3 mg/kg/day for 21 days, first dose immediately prior to reperfusion) significantly improved LV
- [7] PMID 34856183 — Hexarelin (200 µg/kg twice per day) in a mouse elastase-induced abdominal aortic aneurysm model decreased aortic diameter, improved elastin preservation, rescue
- [8] PMID 19931584 — Chronic hexarelin injection (s.c. BID, 30 days) in rats with diet/vitamin D3-induced atherosclerosis suppressed plaque formation, partially reversed HDL-c/LDL-c
- [9] PMID 35126171 — In anesthetized Sprague-Dawley rats, acute hexarelin evoked coronary microvascular dilation via GHS-R1a, nitric oxide, and endothelium-derived hyperpolarization
- [10] PMID 36674509 — Hexarelin (1 µM) protected human neuroblastoma SH-SY5Y SOD1-G93A cells from H2O2-induced cytotoxicity by activating molecules regulating apoptosis and promoting
- [11] PMID 41766237 — In golden hamsters following optic nerve transection, single daily doses of hexarelin (25, 50, 100 µg/kg) dose-dependently increased retinal ganglion cell survi
- [12] PMID 34066741 — Hexarelin inhibited H2O2-induced apoptosis in Neuro-2A cells by improving cell viability, reducing NO release, downregulating caspase-3/7 and Bax mRNA, inhibiti
- [13] PMID 29883404 — Review summarizing hexarelin's role as a potent inducer of PPARγ through CD36 activation, with reported benefits on atherosclerosis, hepatic cholesterol biosynt
- [14] PMID 25045704 — Review: hexarelin has been reported to regulate PPARγ in macrophages and adipocytes and may exert GH-independent cardiovascular and metabolic activities relevan
- [15] PMID 37710348 — In I/R-induced AKI rats, hexarelin pretreatment (100 µg/kg/d for 7 days) mitigated tubular necrosis, improved renal function, and inhibited apoptosis via downre
- [16] PMID 34871336 — In a murine HCl-induced ARDS model, hexarelin (320 µg/kg i.p.) before or after challenge improved lung compliance, reduced immune cell recruitment and neutrophi
- [17] PMID 42619489 — Hexarelin (10 µg/kg i.p.) administered twice (4-h intervals) before or after intranasal MPTP in mice significantly reduced pulmonary histopathological damage, C
- [18] PMID 42758352 — Hexarelin attenuated MPTP-associated pancreatic injury in BALB/c mice, reducing inflammatory markers (CD11b, CD68, IL-1β, TNF-α), apoptosis (caspase-3), and β-a
- [19] PMID 10886488 — Randomized single-blind study: hexarelin (2 µg/kg i.v.) induced striking ACTH/cortisol responses in Cushing's disease patients but not in alcohol-induced pseudo
- [20] PMID 10404825 — Hexarelin's stimulation of HPA axis in healthy young males appears mediated by AVP, not CRH, based on combination studies with desmopressin and CRH.
- [21] PMID 15177700 — In 7 young healthy male volunteers, repetitive hexarelin (4 × 50 µg at 22:00, 23:00, 24:00, 01:00 h) decreased stage 4 slow-wave sleep and EEG delta power, and
- [22] PMID 32893668 — In Wistar rats, hexarelin (0.2 mg/kg) combined with morphine attenuated analgesic tolerance to morphine and enhanced antinociception in tail-flick and hot-plate
- [23] PMID 9186261 — Review noting that in short children, an increase in height velocity has been reported during chronic GHRP treatment; GHRPs including hexarelin have shown clini
- [24] PMID 9465289 — Review noting potential role of GHRPs in treatment of short stature, aging, catabolic states, and dilated cardiomyopathy.
- [25] PMID 10341859 — 1.5 µg/kg twice daily s.c. Subcutaneous (human)
- [26] PMID 8954038 — 0–1.0 µg/kg i.v. (dose-response; 0, 0.125, 0.25, 0.5, 1.0 µg/kg) Intravenous (human)
- [27] PMID 9814463 — 2 µg/kg i.v. Intravenous (human)
- [28] PMID 9231048 — 1 µg/kg i.v. Intravenous (human)
- [29] PMID 9285939 — 1 µg/kg and 2 µg/kg i.v. Intravenous (human)
- [30] PMID 10197083 — 1.5 µg/kg s.c. Subcutaneous (human)
- [31] PMID 7955465 — 1 µg/kg i.v. and 20 µg/kg intranasal Intravenous; intranasal (human)
- [32] PMID 12379504 — Significant responses at 3 µM; maximal effects at ~30 µM In vitro (in_vitro)
- [33] PMID 10790589 — in-prose reference
- [34] PMID 60526442 — in-prose reference
- [35] PMID 34221875 — in-prose reference
- [36] PMID 11578108 — in-prose reference
- [37] PMID 31991924 — in-prose reference
- [38] PMID 42395176 — in-prose reference
- [39] PMID 28400207 — in-prose reference