Hexarelin

Hexarelin (INN: examorelin; sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide derived from GHRP-6 by substitution of 2-methyl-D-tryptophan at the second position. Its primary mechanism is potent agonism at the growth hormone secretagogue receptor subtype 1a (GHS-R1a), a G protein-coupled receptor expressed on anterior pituitary somatotrophs, hypothalamic arcuate neurons, and other tissues.

At least three overlapping mechanisms account for hexarelin's in vivo GH-releasing action: a minor direct stimulatory effect on pituitary somatotrophs; release of endogenous GHRH from hypothalamic neurons (the dominant pathway in adults); and stimulation of an unidentified hypothalamic factor that acts synergistically with GHRH. Because hexarelin engages all three pathways, somatostatin only blunts its GH response rather than abolishing it, unlike the full suppression somatostatin exerts on GHRH-stimulated secretion.

A second distinct receptor, CD36, mediates hexarelin's cardiovascular effects. CD36 is a multifunctional transmembrane glycoprotein (Mr ~84,000) expressed in cardiomyocytes and cardiac microvascular endothelial cells. CD36 activation produces positive inotropic and hemodynamic effects independent of systemic GH, as demonstrated by their persistence in hypophysectomized animals and their absence following GHRH or recombinant GH administration.

At higher doses, hexarelin produces dose-dependent increases in prolactin and ACTH/cortisol via GHS-R1a on corticotroph and lactotroph cells, distinguishing it from the more selective profile of GHRH. The compound has no sequence similarity to ghrelin but functions as a functional ghrelin receptor agonist.

The first human pharmacology study (Ghigo et al., J Clin Endocrinol Metab, 1994; n=12 healthy young volunteers) characterized dose-dependent GH release after intravenous (1-2 µg/kg), subcutaneous (1.5-3 µg/kg), intranasal (20 µg/kg), and oral (20-40 mg) administration. IV hexarelin at 1 µg/kg produced approximately double the GH response of an equivalent GHRH dose, with subcutaneous bioavailability measured at 77%.

A dose-response study (Massoud et al., JCEM, 1996; PMID 8954038) established a GH plateau of 140 mU/L at 1.0 µg/kg (ED50 0.48 µg/kg). When low-dose hexarelin (0.125 µg/kg) was combined with GHRH, GH release reached 115 ± 32.8 mU/L, demonstrating potent synergy. Prolactin rose in a dose-dependent fashion; cortisol showed a step increase at 0.5 µg/kg. Glucose, LH, FSH, and TSH were unaffected.

A 16-week controlled study (Rahim et al., JCEM, 1998; n=12 elderly subjects, 1.5 µg/kg SC twice daily) found mean GH AUC declining from 19.1 ± 2.4 at baseline to 10.5 ± 1.8 µg/L·h at week 16 — a partial but statistically significant attenuation — recovering to 19.4 ± 3.7 four weeks after discontinuation. Serum IGF-I and IGFBP-3 did not change significantly across the study period.

A human cardiac study (Bisi et al., Eur J Pharmacol, 2002; n=24 men with coronary artery disease during bypass surgery) found that acute IV hexarelin significantly increased LVEF, cardiac index, and cardiac output (all P<0.001), sustained for up to 90 minutes, without altering systemic vascular resistance. Recombinant human GH, GHRH, and placebo produced no comparable response, confirming a GH-independent cardiac mechanism.

Animal studies extended these findings. In a mouse LAD-ligation model (0.3 mg/kg/day SC for 21 days; PMC5949285), hexarelin improved LVEF from 37% in controls to 49%, reduced interstitial collagen by ~53%, and lowered troponin-I threefold at 24 hours. A rat coronary-ligation heart failure model (100 µg/kg SC twice daily, 30 days; PMC7018219) linked cardioprotection to PTEN upregulation and Akt/mTOR suppression. In vitro neuroprotection via MAPK/PI3K-Akt modulation was demonstrated in neuroblastoma cells (Meanti et al., Pharmaceuticals, 2021) but remains preclinical. Despite Phase II trials for GH deficiency and congestive heart failure, development was discontinued; hexarelin has never received marketing approval.

Typical dosage: 100 mcg (daily).

In published clinical research, hexarelin was administered by intravenous bolus at 1-2 µg/kg, subcutaneously at 1.5-3 µg/kg, intranasally at 20 µg/kg, and orally at 20-40 mg (Ghigo et al., 1994). The 16-week chronic human study used 1.5 µg/kg SC twice daily, corresponding to approximately 100-120 µg per injection for a 70 kg individual. A GH response plateau was established at approximately 1.0 µg/kg IV in dose-finding work; doses above this level produced minimal additional GH output.

In community and compounding use — entirely outside any regulatory approval — reported doses range from 100 to 200 µg SC per injection, administered one to three times daily. Fasted administration (at minimum 2-3 hours after the last meal) is commonly recommended to maximize GH secretagogue response, as carbohydrates and fatty acids are known to suppress GHS-R1a signaling. Cycling protocols such as five days on, two days off are frequently mentioned in anecdotal reports as a strategy to limit receptor desensitization. This specific cycling approach has no prospective clinical evidence supporting its superiority over continuous dosing; it reflects community empiricism only.

This information reflects published research and reported community practice and is presented for educational purposes only. It does not constitute medical advice and should not be applied to human subjects outside a formally supervised clinical research setting.

Lyophilized (before reconstitution)

Multiple vendor sources cite roughly 24 months at −20°C for Hexarelin lyophilized powder, with a similar profile to CJC-1295/Ipamorelin. Refrigerated (2–8°C) storage is acceptable for shorter active-use windows. Same GH-secretagogue class behavior; no peptide-specific divergence was surfaced in the vendor consensus. Keep dry, sealed, and away from light.

Reconstituted

Commonly cited at ~28 days refrigerated (2–8°C) in bacteriostatic water. Never freeze a reconstituted vial. This is a vendor-derived convention rather than a peptide-specific stability study — the window traces to the 0.9% benzyl alcohol preservative's antimicrobial validation, not to a Hexarelin-specific assay. See the Storage & handling primer for context.

For general storage chemistry (bacteriostatic vs sterile water, freeze-thaw, BUD framework), see Storage & handling.

Last reviewed: July 1, 2026

The most pharmacologically grounded combination is hexarelin with a GHRH analog such as modified GRF(1-29) (CJC-1295 without DAC). GHRH peptides act via the GHRH receptor to prime somatotrophs through cAMP signaling, while hexarelin's GHS-R1a agonism provides a mechanistically distinct, synergistic stimulatory input via intracellular calcium mobilization. The 1996 Massoud et al. dose-response study demonstrated that low-dose hexarelin combined with GHRH produced massive GH release (115 ± 32.8 mU/L) exceeding either agent alone, providing a clear human pharmacological basis for this pairing.

In community practice, hexarelin is anecdotally reported in combination with IGF-1 LR3 for a more pronounced downstream anabolic effect, or alternated with Ipamorelin for longer protocols, since Ipamorelin has a more selective GH-releasing profile with less ACTH and cortisol co-stimulation. No clinical trial data support these community combination protocols; the rationale is empirical and the evidence is entirely anecdotal. Given hexarelin's pronounced cortisol- and prolactin-elevating properties, combining it with other ACTH-stimulating peptides such as GHRP-2 may compound HPA axis activation; anecdotal community guidance generally cautions against this pairing.

Hexarelin is not currently FDA-approved for any indication. It is generally classified as a research compound. Regulatory status varies by country.

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Reported side effects: Desensitization with continuous use, cortisol elevation possible

Hexarelin's principal adverse endocrine effects are dose-dependent elevations in ACTH, cortisol, and prolactin. The Massoud et al. (1996) dose-response study found maximal prolactin increases of approximately 180% and cortisol increases at 0.5 µg/kg; in the 16-week chronic dosing study (Rahim et al., 1998) at 1.5 µg/kg SC twice daily, clinically significant HPA axis over-stimulation and hyperprolactinemia did not occur, and no Cushingoid features or galactorrhea were reported in any published trial.

Tachyphylaxis — partial attenuation of the GH response — is well-documented with continuous use. The Rahim 1998 study recorded a ~45% decline in GH AUC across 16 weeks; this attenuation was reversible within four weeks of discontinuation, and IGF-I levels remained stable throughout, suggesting the overall biological impact on the GH/IGF-I axis was minimal at the dose and frequency studied.

Other adverse effects reported in the literature and in community experience include fluid retention and peripheral edema, paresthesia in the extremities, fatigue, somnolence, headache, and transient flushing. These are consistent with elevated GH and IGF-I activity and are shared with other GH secretagogues.

Hexarelin is not approved by the FDA, EMA, or any other major regulatory agency for any human therapeutic indication. The World Anti-Doping Agency (WADA) classifies it as a prohibited substance under the category of peptide hormones, growth factors, and related substances (S2). Long-term safety in humans has not been characterized in adequately powered controlled trials. The compound should be regarded as investigational, and use outside formally supervised clinical research is not advisable.