Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-24. ← Back to Evidence Library

Hexarelin

examorelin (INN) · His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂ · GHRP-hexarelin

Status: Approved for Adam Greene by Dr. Nova Reyes, 2026-10-24

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

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1. What it is and what people claim it does

Hexarelin (international nonproprietary name examorelin) is a synthetic hexapeptide created in the early 1990s by replacing the D-tryptophan at position 2 of GHRP-6 with a methylated D-2-methyl-tryptophan residue. It belongs to the growth-hormone-releasing peptide (GHRP) family and acts primarily on two targets:

1. The ghrelin / growth hormone secretagogue receptor (GHS-R1a) in the hypothalamus and pituitary gland, triggering an acute surge of growth hormone (GH). ^{R2, R3}
2. A non-GH cardiac receptor (identified in preclinical work as the scavenger receptor CD36) on heart muscle and blood-vessel cells, which researchers in Turin, Italy investigated around 1999–2002 for short-term effects on heart contractility. ^R6–R9

Online peptide vendors and bodybuilding forums market hexarelin vials as the "strongest GHRP" for muscle growth, fat loss, tendon repair, and "cardioprotection," while recommending short cycles because its pituitary effect wears down quickly. Pharmacia & Upjohn and Europeptides studied examorelin in small human endocrine and acute cardiac trials in the 1990s and early 2000s, then abandoned clinical development without seeking approval anywhere in the world.

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2. What the human evidence actually shows

The Open Peptide Project's reading: Limited for single-dose pituitary GH stimulation, Very limited for multi-week adult IGF-1/body composition, acute hospital IV cardiac ejection-fraction changes, and pediatric short stature, and No human data for gray-market muscle building, fat loss, or injury recovery.

Indication	Route studied	Evidence rating	Summary of human studies
Acute pituitary GH release / endocrine testing	IV, subcutaneous, intranasal, oral	Limited	Multiple small human crossover studies (6 to 19 volunteers) confirm potent single-dose GH release accompanied by rises in prolactin, ACTH, and cortisol. R2–R5
Adult IGF-1, lean mass, fat mass, and bone density	Subcutaneous injection	Very limited	1 randomized dose-comparison study in 24 healthy older adults found that repeated subcutaneous dosing blunted GH release by ~43–55%, failed to significantly raise serum IGF-1 or IGFBP-3, and produced zero change in fat mass, lean body mass, or bone mineral density. R1
Acute left-ventricular ejection fraction (LVEF)	Acute hospital IV bolus	Very limited	4 small acute IV studies (7 healthy men, 7 GH-deficient adults, 13 cardiomyopathy patients, and 24 coronary-bypass patients) found a transient 15–90 minute rise in LVEF in healthy, GH-deficient, and ischemic heart patients, no improvement in dilated cardiomyopathy, and no multi-week trials. R6–R9
Pediatric short stature	Intranasal spray	Very limited	1 unblinded single-arm pilot in 7 short prepubertal children showed >50% attenuation of the acute GH response within the first week, alongside higher IGF-1 and growth velocity vs the prior year without a control group. R10
Muscle building, fat loss, or tissue healing in athletes/adults	Subcutaneous injection	No human data	No human trials show muscle hypertrophy, strength gain, fat loss, or tendon healing.

Pituitary growth-hormone release, receptor desensitization, and the negative adult body-composition trial

In acute human pharmacology studies led by Ezio Ghigo's group at the University of Turin and Márta Korbonits's group in London, a single IV, subcutaneous, intranasal, or high oral dose of hexarelin triggered a rapid, dose-dependent spike in blood growth hormone peaking within 30 to 60 minutes—substantially larger than a maximal dose of endogenous growth-hormone-releasing hormone (GHRH). ^{R2, R3, R5}

However, human trials revealed two major limitations that directly contradict gray-market bodybuilding claims:

• Rapid pituitary desensitization (tachyphylaxis): When healthy volunteers received a continuous hospital hexarelin infusion, a second dose at the end of the infusion barely released any growth hormone at all (homologous desensitization, meaning the receptor stops responding to repeated doses of the same trigger). ^R4 Even with intermittent dosing, the pituitary response blunts substantially.
• No increase in IGF-1 and no change in lean mass or fat mass in older adults (Rahim, O'Neill & Shalet, 1998): In the pivotal multi-month human study of subcutaneous hexarelin, 24 healthy elderly adults were randomized to two subcutaneous dosing frequencies over a multi-month treatment course followed by a washout period. Peak GH Area Under the Curve dropped significantly after the first month (43% to 55% attenuation compared with the start of treatment) and returned completely to baseline after stopping. Crucially, serum IGF-1 and IGFBP-3 did not change significantly at any point during the study, and neither lean body mass, fat mass, nor bone mineral density changed. ^R1 That illustrates why a brief daily GH spike after an injection is a biomarker change, not an automatic increase in circulating IGF-1 or muscle mass.

Acute cardiac ejection-fraction studies (single hospital IV doses)

Between 1999 and 2002, Turin researchers published four small acute human studies testing whether a single slow intravenous injection of hexarelin altered left-ventricular ejection fraction (LVEF, the percentage of blood pumped out of the left ventricle with each beat) over 60 to 90 minutes:

• Healthy men (Bisi et al., 1999a) and GH-deficient adults (Bisi et al., 1999b): In 7 healthy male volunteers studied with radionuclide angiography, an acute IV bolus of hexarelin transiently raised LVEF from 64.7% ± 1.6% to 70.7% ± 3.0% at 30 minutes (p < 0.02) without changing heart rate or mean blood pressure. ^R6 In 7 adults with severe GH deficiency, the same acute IV bolus raised LVEF from 54.0% ± 2.7% to 63.3% ± 2.5% (p < 0.01) even though their pituitary GH response was negligible, indicating a direct non-GH vascular or myocardial effect. ^R7
• Ischemic vs dilated cardiomyopathy (Imazio et al., 2002): In 13 men with severe heart failure (baseline LVEF < 30%), acute IV hexarelin transiently raised LVEF in the 5 patients with ischemic cardiomyopathy (from 21.6% ± 4.1% to 25.0% ± 5.0%, p < 0.02), but produced no change at all in the 8 patients with dilated cardiomyopathy (22.0% vs 22.8%). ^R8
• Coronary artery bypass surgery (Broglio et al., 2002): In 24 men undergoing coronary bypass surgery who were randomized intraoperatively to acute IV hexarelin, recombinant human GH, or saline (8 per group), hexarelin acutely increased LVEF (from 52.5% to 60.4%), cardiac index, and pulmonary capillary wedge pressure while decreasing systemic vascular resistance for 15–60 minutes; neither recombinant GH nor saline changed cardiac function. ^R9
• What is missing: Every one of these cardiac studies measured a 15-to-90-minute hemodynamic response to a single hospital IV bolus. No randomized trial has ever tested whether repeated hexarelin dosing improves exercise capacity, hospitalization, or survival in people with heart disease.

Pediatric short stature

• Single-arm intranasal pilot in 7 short children (Klinger, Laron et al., 1996): Seven prepubertal children with familial short stature used intranasal hexarelin in an unblinded single-arm study. Within the first several days, the pituitary GH response to a dose dropped by more than 50% (p < 0.03) and stayed blunted afterward. The authors reported higher serum IGF-1, serum phosphate, and procollagen-III levels and faster annualized height velocity compared with the pre-study year, with no untreated control group. ^R10

Study details — click to expand all clinical trial rows (doses, schedules, outcomes, and side effects)

Study (Year)	Design & Population	Route, Dose & Schedule	Primary / Key Outcomes	Adverse Events & Dropouts	Funding & Disclosures
Rahim, O'Neill & Shalet (1998) R1	Randomized open-label parallel dose-frequency study; 24 healthy elderly adults (12 men, 12 women; mean age 69 years, range 64–76; 12 per group)	Subcutaneous: 1.5 mcg/kg SC injected either twice daily (BID) or once daily (OD) for 16 weeks, followed for a 4-week washout (to week 20)	GH AUC fell significantly from week 1 to week 4 in both groups (~55% attenuation in BID, ~43% in OD at week 16 vs week 1) and returned completely to baseline by week 20. No significant change in serum IGF-1 or IGFBP-3; no change in fat mass, lean body mass, or bone mineral density.	Mild bruising at injection sites and transient increased appetite in a few subjects; no serious adverse events reported in abstract.	Christie Hospital, Manchester, UK; hexarelin supplied by Pharmacia & Upjohn.
Ghigo et al. (1994) R2	Acute human dose-ranging & route-comparison study; healthy young adult volunteers	IV, SC, intranasal, and oral: IV (0.5, 1, or 2 mcg/kg), SC (1.5 or 3 mcg/kg), intranasal (12.5, 20, or 30 mcg/kg), and oral (20 or 40 mg capsules)	Potent dose-dependent GH release across all 4 routes; 1 mcg/kg IV hexarelin released more GH than a maximal 2 mcg/kg IV dose of GHRH (p < 0.02); GH half-life ~55 min after 1–2 mcg/kg IV.	Transient mild facial flushing after IV administration.	University of Turin, Italy; peptide supplied by Europeptides.
Korbonits et al. (1999) R3	Randomized crossover endocrine study; 19 healthy young men (divided into two sub-studies of 10 and 9 men)	IV bolus: 100 mcg hexarelin IV alone or combined with GHRH (100 mcg), CRH (100 mcg), or AVP (1 IU)	Hexarelin caused a massive GH rise (153.7 ± 12.1 mU/L vs 11.4 ± 4.0 mU/L on saline, p < 0.001) and acted synergistically with GHRH (220.4 mU/L). It also significantly increased serum ACTH (p = 0.036), cortisol (p = 0.003), and prolactin (p < 0.001), without changing LH, FSH, or TSH.	0 dropouts; transient facial flushing noted after IV bolus.	St. Bartholomew's Hospital, London, UK.
Arvat et al. (1999) R4	Crossover pituitary desensitization study; 14 healthy young volunteers	IV infusion + bolus: 24-hour continuous IV infusion of GHRH (2 mcg/kg/h) or hexarelin (2 mcg/kg/h), followed at 24 hours by a 2 mcg/kg IV bolus of GHRH or hexarelin	Continuous 24-hour hexarelin infusion caused profound homologous desensitization (almost complete loss of GH response to a subsequent hexarelin bolus), while preserving responsiveness to GHRH.	0 dropouts; well tolerated during 24-hour hospital monitoring.	University of Turin, Italy; supported by MURST and Europeptides.
Maccario et al. (2002) R5	Randomized crossover deconvolution study; 6 healthy men (mean age 27.6 ± 1.2 years)	IV bolus: Single morning IV injection of hexarelin (2.0 mcg/kg), GHRH (2.0 mcg/kg), or saline, sampled every 15 min from -30 to +240 min	Hexarelin increased GH secretory burst mass 20-fold (vs 5-fold with GHRH) and also stimulated 3-fold prolactin, 2.5-fold ACTH, and 1.7-fold cortisol secretory burst mass (p < 0.01 vs saline and GHRH).	0/6 dropped out; mild transient facial flushing.	University of Turin & University of Virginia; supported by Pharmacia & Upjohn and Fondazione Studio Malattie Endocrinometaboliche.
Bisi et al. (1999a) R6	Acute open-label hemodynamic study; 7 healthy male volunteers (mean age 27.2 ± 1.6 years)	IV: 2.0 mcg/kg IV injected slowly over 5 min during equilibrium radionuclide angiography + gated SPECT	LVEF rose from 64.7% ± 1.6% at baseline to 70.7% ± 3.0% at 30 min (p < 0.02), peaking at 15–30 min and lasting ~60 min, due to reduced left-ventricular end-systolic volume without changes in mean BP or heart rate.	0/7 dropped out; transient facial flushing in a minority of subjects.	University of Turin, Italy; supported by MURST and Europeptides.
Bisi et al. (1999b) R7	Acute controlled hemodynamic study; 7 adult GH-deficient patients (ages 22–65, post-hypophysectomy) and 9 healthy male controls	IV: 2.0 mcg/kg IV injected slowly over 5 min during radionuclide angiography (with a control saline session in 5 GH-deficient patients)	Despite severely blunted GH release in GH-deficient patients (3.1 vs 62.6 mcg/L in controls), LVEF rose from 54.0% ± 2.7% to 63.3% ± 2.5% (p < 0.01 vs baseline and saline), matching the acute LVEF rise in healthy controls (64.7% to 71.0%).	0 dropouts; no change in catecholamines, blood pressure, or heart rate.	University of Turin, Italy.
Imazio et al. (2002) R8	Acute open-label hemodynamic study; 13 men with severe heart failure (LVEF < 30%: 8 dilated cardiomyopathy [DCM], 5 ischemic cardiomyopathy [ICM]), compared against 7 normal subjects and 7 GH-deficient subjects	IV: 2.0 mcg/kg IV bolus monitored by echocardiography and radial-artery tonometry for 90 min	Mixed by cause of heart failure: In 5 ICM patients, LVEF rose transiently from 21.6% ± 4.1% to 25.0% ± 5.0% (p < 0.02). In 8 DCM patients, LVEF did NOT change (22.0% ± 6.4% vs 22.8% ± 6.5%), even though GH rose similarly in both groups.	0/13 dropped out; no acute arrhythmias or hypotension reported.	University of Turin, Italy; supported by Europeptides and Fondazione Studio Malattie Endocrinometaboliche.
Broglio et al. (2002) R9	Randomized, double-blind, placebo- and active-controlled acute intraoperative study; 24 male coronary artery bypass patients (mean age 62.3 ± 1.9 years, pre-op LVEF 51.0% ± 1.6%; 8 per arm)	IV: 2.0 mcg/kg IV hexarelin, 8.0 mcg/kg recombinant human GH, or saline over 3 min via central venous catheter after weaning from cardiopulmonary bypass	Only hexarelin acutely raised LVEF (from 52.5% ± 2.2% to 60.4% ± 2.5%, p < 0.05), cardiac index (from 2.2 to 2.6 L/min/m²), and wedge pressure while lowering systemic vascular resistance from 15 to 60 min; r-hGH and saline had no acute hemodynamic effect.	0/24 dropped out; no acute perioperative adverse events attributed to hexarelin.	University of Turin & Pisa, Italy; supported by Pharmacia & Upjohn and MIUR.
Klinger, Laron et al. (1996) R10	Open-label, single-arm pilot trial (no control group); 7 prepubertal short children (6 boys, 1 girl; ages 4.8–10.8 years)	Intranasal: 60 mcg/kg three times daily via nasal spray for up to 8 months (3 children for 3 months, 4 children for 6–8 months)	Pituitary GH response to hexarelin blunted by >50% after 7 days (p < 0.03) and remained attenuated at 3 months; serum IGF-1 rose from 10.6 ± 3.2 to 16.5 ± 6.8 nmol/L (p < 0.03) and annualized growth velocity increased from 5.3 ± 0.8 to 8.3 ± 1.7 cm/year vs prior year.	0/7 dropped out for adverse events; mild nasal irritation and transient increased appetite early in treatment; slight decrease in TSH within normal range.	Schneider Children's Medical Center, Petah Tikva, Israel; hexarelin supplied by Europeptides.

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3. Known risks, side effects, and long-term unknowns

Because hexarelin was dropped before any large Phase 2 or Phase 3 safety trial was conducted, its human safety record is limited to small endocrine and acute hospital studies:

• Consistent cortisol, ACTH, and prolactin spikes: Unlike more selective ghrelin-receptor agonists (such as ipamorelin), hexarelin reliably stimulates the hypothalamic-pituitary-adrenal axis and lactotroph cells, increasing ACTH (~2.5-fold), cortisol (~1.7-fold), and prolactin (~3-fold) after each injection. ^{R3, R5} Repeated daily elevations in cortisol and prolactin work against the anabolic and body-composition goals for which gray-market buyers take the peptide, and chronic hyperprolactinemia can suppress reproductive hormones (LH/testosterone) or cause gynecomastia and sexual dysfunction.
• Facial flushing and appetite stimulation: Transient warmth or flushing of the face and upper body is common immediately after intravenous or subcutaneous injection, along with increased hunger (driven by ghrelin-receptor activation) and occasional injection-site bruising. ^{R1, R2, R10}
• Slight TSH suppression in pediatric use: In the 7-child intranasal pilot study, serum thyroid-stimulating hormone (TSH) declined slightly during multi-month administration while remaining within the normal reference range. ^R10
• Insulin resistance and fluid retention (GH secretagogue class risk): Any compound that repeatedly raises circulating growth hormone can reduce insulin sensitivity and raise fasting blood glucose or fluid retention, though hexarelin's rapid pituitary desensitization blunted sustained GH/IGF-1 elevation in the 24-adult trial. ^R1
• Complete lack of long-term human safety data: No human study has followed people taking hexarelin for more than a few months, leaving long-term cardiovascular, metabolic, pituitary, and cancer-related risks unstudied.

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4. Regulatory and compounding status

Jurisdiction / Body	Current Status	Details
United States (FDA — Drugs)	Not FDA-approved	Examorelin / hexarelin has never been approved as a human or veterinary drug in the United States. R11
United States (FDA — 503A & 503B Compounding)	Not on 503A or 503B Lists (illegal to compound for humans)	Hexarelin does not appear in Category 1 on either the FDA 503A Bulk Drug Substances List (updated May 14, 2026) or the 503B List (updated Mar 21, 2025), has no USP/NF monograph for human compounding, and is not a component of an FDA-approved drug. Compounding pharmacies in the US cannot legally compound hexarelin for human prescriptions. R11
Worldwide National Regulators (EMA, MHRA, PMDA, TGA, Health Canada)	Not approved anywhere worldwide	Clinical development by Europeptides and Pharmacia & Upjohn ended after small early-2000s trials; no country has granted marketing authorization.
World Anti-Doping Agency (WADA 2026)	Explicitly prohibited at all times (Section S2.2.4)	Named directly on the 2026 WADA Prohibited List under Section S2.2.4 (Growth Hormone Releasing Factors — GH-releasing peptides [GHRPs]): "GH-releasing peptides (GHRPs) [e.g. alexamorelin, examorelin (hexarelin), GHRP-1, GHRP-2 (pralmorelin), GHRP-3, GHRP-4, GHRP-5 and GHRP-6]". Banned both in- and out-of-competition. R12

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5. Quality, contamination, and gray-market risks

Every vial sold to consumers comes from unregulated research-chemical and gray-market suppliers:

1. Unverified identity and substitution with cheaper GHRPs: Because GHRP-2, GHRP-6, ipamorelin, and hexarelin are all small white lyophilized powders that cause similar post-injection flushing or hunger, buyers cannot tell without third-party liquid chromatography–mass spectrometry (LC-MS) testing whether a vial actually contains methylated D-2-methyl-Trp hexarelin or a cheaper GHRP substitute.
2. TFA salt and bacterial endotoxin: Unregulated peptide synthesis frequently leaves trifluoroacetic acid (TFA) counter-ions, residual organic solvents, or bacterial endotoxin in vials labeled "for research use only."
3. Anti-doping detection in athletes: Accredited WADA anti-doping laboratories routinely screen urine and blood samples for hexarelin and its peptidic metabolites using high-resolution mass spectrometry, and athletes have received multi-year competition bans for GHRP positives. ^R12

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6. Who should be especially cautious

• Competitive and drug-tested athletes: Hexarelin (examorelin) is explicitly banned at all times under WADA S2.2.4 and is readily detected in urine anti-doping screens. ^R12
• People with heart failure or cardiomyopathy tempted by "cardioprotective" claims: Despite online claims that hexarelin heals the heart, human cardiac evidence consists solely of 15-to-90-minute monitoring after a single hospital IV dose, and the peptide failed to improve ejection fraction at all in patients with dilated cardiomyopathy. ^R6–R9
• People with Cushing's syndrome, elevated prolactin, adrenal disorders, diabetes, or active cancer: Hexarelin acutely elevates ACTH, cortisol, and prolactin alongside growth hormone. ^{R3, R5}
• Children and adolescents: Outside a single 7-child hospital study conducted in the 1990s ^R10, hexarelin's effects on growing bones, pituitary desensitization, and thyroid/adrenal axes in youth are unestablished.

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7. Open questions and research gaps

• Why acute GH spikes failed to raise IGF-1 or lean mass in older adults: In the 24-adult subcutaneous trial, pituitary desensitization cut the GH response roughly in half and serum IGF-1 never rose significantly. ^R1 Whether any intermittent schedule avoids desensitization while producing real changes in human muscle mass or physical function has never been shown.
• No chronic human cardiac trials: Why Pharmacia & Upjohn discontinued examorelin after the 1999–2002 acute IV ejection-fraction studies—without publishing a multi-week oral or subcutaneous heart-failure trial—has never been fully detailed in peer-reviewed literature. ^R6–R9

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8. References

• ^R1 Rahim A, O'Neill PA, Shalet SM. Growth hormone status during long-term hexarelin therapy. Clin Endocrinol (Oxf). 1998;48(4):463–469. PMID 9589671 · doi:10.1046/j.1365-2265.1998.00465.x
• ^R2 Ghigo E, Arvat E, Gianotti L, et al. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. J Clin Endocrinol Metab. 1994;78(3):693–698. PMID 8126144 · doi:10.1210/jcem.78.3.8126144
• ^R3 Korbonits M, Kaltsas G, Perry LA, et al. The growth hormone secretagogue hexarelin stimulates the hypothalamo-pituitary-adrenal axis via arginine vasopressin. J Clin Endocrinol Metab. 1999;84(7):2489–2495. PMID 10469018 · doi:10.1210/jcem.84.7.5811
• ^R4 Arvat E, Maccario M, Di Vito L, et al. Endocrine activities of growth hormone secretagogues inhumans: homologous and heterologous desensitization. J Clin Endocrinol Metab. 1999;84(10):3744–3749. PMID 10516483 · doi:10.1210/jcem.84.10.6061
• ^R5 Maccario M, Veldhuis JD, Broglio F, et al. Impact of two-day treatment with hexarelin or growth hormone-releasing hormone on the pulsatile and algorithmic secretogranin/hormone release of GH, prolactin, ACTH and cortisol in humans. Eur J Endocrinol. 2002;146(3):313–320. PMID 11888836 · doi:10.1530/eje.0.1460313
• ^R6 Bisi G, Podio V, Valetto MR, et al. Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest. 1999;22(4):266–272 (and Bisi G et al., Eur J Pharmacol. 1999;381(1):31–38, PMID 10342360 · doi:10.1016/s0014-2999(99)00530-0).
• ^R7 Bisi G, Podio V, Valetto MR, et al. Cardiac effects of hexarelin in hypopituitary adults. Eur J Pharmacol. 1999;381(1):31–38 & J Endocrinol Invest. 1999;22(4):266–272. PMID 10528131 · doi:10.1007/BF03343555
• ^R8 Imazio M, Bobbio M, Broglio F, et al. GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy. Eur J Heart Fail. 2002;4(2):185–191. PMID 11959048 · doi:10.1016/s1388-9842(01)00233-1
• ^R9 Broglio F, Guarracino F, Benso A, et al. Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery. Eur J Pharmacol. 2002;448(2–3):193–200. PMID 12144941 · doi:10.1016/s0014-2999(02)01934-9
• ^R10 Klinger B, Silbergeld A, Deghenghi R, Frenkel J, Laron Z. Desensitization from long-term intranasal treatment with hexarelin does not interfere with biological effects in short children. Eur J Endocrinol. 1996;134(6):716–719. PMID 8766941 · doi:10.1530/eje.0.1340716
• ^R11 US Food and Drug Administration (FDA). 503A Bulk Drug Substances List (updated May 14, 2026) and 503B Bulk Drug Substances List (updated Mar 21, 2025).
• ^R12 World Anti-Doping Agency (WADA). 2026 Prohibited List — International Standard, Section S2.2.4 (Growth Hormone Releasing Factors: GH-releasing peptides [GHRPs], explicitly naming examorelin (hexarelin); effective Jan 1, 2026).

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Disclaimer

This page is for education and harm reduction. It is not medical advice and not a recommendation to use this compound. Please talk to a clinician you trust before making medical decisions, and report adverse events to FDA MedWatch (https://www.fda.gov/safety/medwatch).