Hexarelin Research: Ghrelin Receptor, CD36 and the Heart

Hexarelin is one of the most studied synthetic growth hormone-releasing peptides, and one of the few with human heart data. This article covers how it works, what cell, rodent and human studies found, and where the evidence stops.

What is hexarelin?

Hexarelin is a hexapeptide (a chain of six amino acids): His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2. It is a close analogue of GHRP-6 in which the developers swapped D-tryptophan for 2-methyl-D-tryptophan, described as chemically more stable. In the first published study, in infant and adult rats, it released growth hormone (GH) about as effectively as GHRP-6 (Deghenghi et al., 1994). The first human study, run with the Italian company Mediolanum Farmaceutici, was placebo-controlled in 12 healthy men: GH peaked at about 30 minutes and was back to baseline within four hours (Imbimbo et al., 1994).

How does hexarelin work?

Its GH effect runs through the growth hormone secretagogue receptor type 1a (GHS-R1a), cloned in 1996 as the target of synthetic GH secretagogues (Howard et al., 1996). Its natural partner, the stomach hormone ghrelin, was identified in 1999 (Kojima et al., 1999), so GHS-R1a is now called the ghrelin receptor.

Hexarelin acts at more than one level. In sheep, it increased release of growth hormone-releasing hormone (GHRH) from the hypothalamus without changing somatostatin, the hormone that holds GH back (Guillaume et al., 1994). In people, the GH effect depends on working GHRH signalling: in four men with an inherited GHRH receptor fault, hexarelin produced no GH rise, yet prolactin, ACTH and cortisol rose normally (Maheshwari et al., 1999). Given with GHRH, it released more GH than the two did separately, added together (Massoud et al., 1996a). Hexarelin also binds a second receptor, CD36, covered in the heart section below.

What do human studies show?

Growth hormone release

In 12 healthy young adults, hexarelin produced about twice the GH response of GHRH in the same study, and the response repeated reliably (Ghigo et al., 1994). In a study of 60 people, the response was larger in pubertal children and young adults than in prepubertal children and people aged 66 to 81 (Arvat et al., 1997).

Prolactin, ACTH and cortisol

Hexarelin is not selective for GH. In healthy men, GH, prolactin and cortisol all rose, more so as the amount given increased; a small amount combined with GHRH gave large GH release, a moderate prolactin rise and no cortisol rise (Massoud et al., 1996b). Prolactin and cortisol responses were similar at every age, while the ACTH response varied with age (Arvat et al., 1997). In seven healthy men, hexarelin raised cortisol, whereas growth hormone itself did not (Bisi et al., 1999a).

After 16 weeks of repeated treatment in adults, the picture changed: the cortisol response was smaller than at the start, ACTH and prolactin responses were unchanged, and 24-hour urine cortisol did not change. The authors found no sign of over-stimulation (Rahim et al., 1999).

Does the GH response fade with repeated exposure?

Partly. Several human studies report attenuation, also called desensitisation, that eased after treatment stopped.

• Within hours: in six healthy men, a second exposure two hours after the first gave a lower GH peak, and the extra boost from combining hexarelin with GHRH was lost (Massoud et al., 1996a).
• Over months, in children: in seven short children treated for 6 to 10 months, the GH response roughly halved after seven days, then held steady, and partly recovered three months after stopping. Growth velocity still increased. This was a single group with no controls (Klinger et al., 1996).
• Over months, in adults: across 16 weeks the GH response fell to a little over half its starting level, then returned to baseline four weeks after stopping. IGF-1, body fat, lean mass and bone density did not change (Rahim et al., 1998).

Not every study agrees: in older adults, 8 to 15 days of intermittent treatment did not reduce the response (Ghigo et al., 1996). The studies are too small to explain the difference.

Why is hexarelin studied in heart research?

Because it binds CD36, a receptor on heart muscle and blood vessel cells, and has shown heart effects in rats and people that did not depend on growth hormone.

Cell and isolated heart studies

Researchers in Montreal found an 84 kDa hexarelin binding protein in rat heart membranes that other GH secretagogues did not bind. In isolated rat hearts, hexarelin raised coronary perfusion pressure, a sign of narrowing of the heart's arteries (Bodart et al., 1999). In 2002 they identified the protein as CD36, found on heart muscle cells and small blood vessel linings; the coronary effect was missing in hearts from mice lacking CD36 (Bodart et al., 2002). Hexarelin's binding site on CD36 overlaps the site for oxidised LDL cholesterol (Demers et al., 2004).

Rodent studies

• In rats with the pituitary removed, so no GH response was possible, a week of hexarelin protected isolated hearts from ischaemia-reperfusion damage; a GH-releasing peptide that does not bind the heart did not (Locatelli et al., 1999).
• In rats after an induced heart attack, two weeks of hexarelin increased cardiac output about as much as GH did (Tivesten et al., 2000).
• In atherosclerosis-prone mice on a lipid-rich diet, hexarelin reduced artery lesions; in macrophages it increased cholesterol export through a PPAR-gamma pathway linked to both CD36 and GHS-R1a (Avallone et al., 2006).

Human studies

Every human heart study we found tested a single exposure over minutes to hours. Left ventricular ejection fraction (the share of blood pumped out with each beat) rose:

• from 64% to about 71% in seven healthy men, for up to an hour, while growth hormone itself had no effect (Bisi et al., 1999a);
• in seven men with severe GH deficiency, even though GH barely moved (Bisi et al., 1999b);
• in five patients with ischaemic cardiomyopathy, but not in eight with dilated cardiomyopathy (Imazio et al., 2002);
• in a study of 24 men during heart bypass surgery, together with cardiac output, for up to 90 minutes, while GHRH, growth hormone and placebo had no such effect (Broglio et al., 2002).

This points to a short-lived effect on heart contraction that does not depend on GH. It does not show which receptor is responsible: GHS-R1a is also found in the heart and blood vessels (Mao et al., 2014), and CD36 was first linked to hexarelin through coronary narrowing, not protection. There are no long-term human heart trials.

Hexarelin vs ipamorelin

Both activate the ghrelin receptor. Ipamorelin, a five-amino-acid peptide from Novo Nordisk, was described in 1998 as the first selective GH secretagogue: in swine it released GH without raising ACTH or cortisol above GHRH levels, while GHRP-6 and GHRP-2 did raise them (Raun et al., 1998). Hexarelin was not in that comparison, but in human studies it raised prolactin, ACTH and cortisol alongside GH. We found no head-to-head human study and no report of ipamorelin binding CD36. See the hexarelin vs ipamorelin comparison.

How is hexarelin different from CJC-1295 and tesamorelin?

CJC-1295 and tesamorelin are GHRH analogues, acting on the GHRH receptor rather than the ghrelin receptor. CJC-1295 raised GH and IGF-1 for days after a single exposure in healthy adults (Teichman et al., 2006). Tesamorelin reduced visceral abdominal fat in a randomised trial of 412 people with HIV (Falutz et al., 2007) and was approved in the US in 2010 for that use (see tesamorelin research). Because hexarelin's GH effect needs GHRH signalling and is amplified by GHRH, research has paired the two pathways (see CJC-1295 and ipamorelin research). Tesamorelin has large randomised trials behind it; hexarelin, as far as we could find, has none.

Is hexarelin approved, and is it allowed in sport?

Hexarelin is not an approved medicine in the UK, the EU or the US. As far as we could find, its clinical development did not go beyond small studies, and no hexarelin trial is registered on ClinicalTrials.gov. Research-grade material is supplied for laboratory research only (see the hexarelin compound page). The World Anti-Doping Agency's 2026 Prohibited List names examorelin (hexarelin) among the GH-releasing peptides in section S2.2.4, prohibited at all times (WADA, 2026). Ipamorelin, CJC-1295 and tesamorelin are in the same section.

What is not known?

• Long-term safety in people. The longest human studies lasted months, in small groups.
• What the heart findings mean. Whether brief rises in ejection fraction matter, and which receptor drives them in people, is untested.
• How the fading response behaves. Results conflict, and no study went beyond months.
• Whether rodent metabolic findings carry over. In insulin-resistant mice, 12 days of hexarelin improved glucose and insulin tolerance and lowered triglycerides (Mosa et al., 2017). There are no human data.
• Replication. Much of the human work came from a few groups, notably at the University of Turin, and little has been repeated since the early 2000s.

The bottom line

Hexarelin is a potent but non-selective GH secretagogue with a second receptor, CD36. Human studies show strong, short-lived GH release, rises in prolactin, ACTH and cortisol, a response that partly fades, and a brief GH-independent effect on heart contraction. The heart and metabolic findings rest mainly on rodent work and single-session human studies, and there are no large trials.

References

1. Arvat E, et al. (1997). The GH, prolactin, ACTH and cortisol responses to Hexarelin, a synthetic hexapeptide, undergo different age-related variations. European Journal of Endocrinology. PubMed 9437229
2. Avallone R, et al. (2006). A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway. Molecular Endocrinology. PubMed 16959872
3. Bisi G, et al. (1999a). Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. Journal of Endocrinological Investigation. PubMed 10342360
4. Bisi G, et al. (1999b). Cardiac effects of hexarelin in hypopituitary adults. European Journal of Pharmacology. PubMed 10528131
5. Bodart V, et al. (1999). Identification and characterization of a new growth hormone-releasing peptide receptor in the heart. Circulation Research. PubMed 10532947
6. Bodart V, et al. (2002). CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circulation Research. PubMed 11988484
7. Broglio F, et al. (2002). Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery. European Journal of Pharmacology. PubMed 12144941
8. Deghenghi R, et al. (1994). GH-releasing activity of Hexarelin, a new growth hormone releasing peptide, in infant and adult rats. Life Sciences. PubMed 7910650
9. Demers A, et al. (2004). Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study. Biochemical Journal. PubMed 15176951
10. Falutz J, et al. (2007). Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. PubMed 18057338
11. Ghigo E, et al. (1994). Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. Journal of Clinical Endocrinology and Metabolism. PubMed 8126144
12. Ghigo E, et al. (1996). Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging. European Journal of Endocrinology. PubMed 8921821
13. Guillaume V, et al. (1994). Growth hormone (GH)-releasing hormone secretion is stimulated by a new GH-releasing hexapeptide in sheep. Endocrinology. PubMed 7915227
14. Howard AD, et al. (1996). A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. PubMed 8688086
15. Imazio M, et al. (2002). GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy. European Journal of Heart Failure. PubMed 11959048
16. Imbimbo BP, et al. (1994). Growth hormone-releasing activity of hexarelin in humans. A dose-response study. European Journal of Clinical Pharmacology. PubMed 7957536
17. Klinger B, et al. (1996). Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children. European Journal of Endocrinology. PubMed 8766941
18. Kojima M, et al. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. PubMed 10604470
19. Locatelli V, et al. (1999). Growth hormone-independent cardioprotective effects of hexarelin in the rat. Endocrinology. PubMed 10465272
20. Maheshwari HG, et al. (1999). Selective lack of growth hormone (GH) response to the GH-releasing peptide hexarelin in patients with GH-releasing hormone receptor deficiency. Journal of Clinical Endocrinology and Metabolism. PubMed 10084578
21. Mao Y, et al. (2014). The cardiovascular action of hexarelin. Journal of Geriatric Cardiology. PubMed 25278975
22. Massoud AF, et al. (1996a). The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity. Clinical Endocrinology. PubMed 8762732
23. Massoud AF, et al. (1996b). Hexarelin-induced growth hormone, cortisol, and prolactin release: a dose-response study. Journal of Clinical Endocrinology and Metabolism. PubMed 8954038
24. Mosa R, et al. (2017). Hexarelin, a Growth Hormone Secretagogue, Improves Lipid Metabolic Aberrations in Nonobese Insulin-Resistant Male MKR Mice. Endocrinology. PubMed 28977588
25. Rahim A, et al. (1998). Growth hormone status during long-term hexarelin therapy. Journal of Clinical Endocrinology and Metabolism. PubMed 9589671
26. Rahim A, et al. (1999). The effect of chronic hexarelin administration on the pituitary-adrenal axis and prolactin. Clinical Endocrinology. PubMed 10341859
27. Raun K, et al. (1998). Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology. PubMed 9849822
28. Teichman SL, et al. (2006). Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Journal of Clinical Endocrinology and Metabolism. PubMed 16352683
29. Tivesten A, et al. (2000). The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction. Endocrinology. PubMed 10614623
30. World Anti-Doping Agency (2026). The 2026 Prohibited List, section S2.2.4, Growth hormone releasing factors. wada-ama.org