Hexarelin

Hexarelin (development code EP-23905, INN name Examorelin) is a synthetic hexapeptide made of six amino acids with a molecular weight of 887.03 Daltons. Among growth hormone secretagogues (GHS or GHRPs), Hexarelin is considered one of the most potent research peptides for the acute release of growth hormone (GH). Besides research into growth disorders, Hexarelin is studied in experimental settings mainly for its cardioprotective, heart-protecting properties.

What is Hexarelin (Examorelin)?

Hexarelin is a synthetically produced peptide made of six amino acids and ranks among the strongest known growth hormone secretagogues (GHS). These peptide agents stimulate a significant, acute release of the body's own growth hormone. The hexapeptide was developed in the 1990s by the Italian research group led by Emanuele Ghigo and was studied in clinical trials under the INN name Examorelin. The amino acid sequence His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 is structurally similar to the body's own hunger hormone ghrelin, but it is produced entirely synthetically.

Compared to other GHRP peptides, Hexarelin has a unique feature: it also binds to the CD36 receptor on cardiomyocytes (heart muscle cells). This gives Hexarelin cardioprotective effects that occur completely independently of growth hormone levels. These heart-protecting effects are well documented in preclinical animal studies [1][2].

How is Hexarelin used?

In the clinical studies of the 1990s, Hexarelin was tested via different routes of administration: intravenously (1-2 µg/kg), subcutaneously (1.5-3 µg/kg), intranasally (20 µg/kg), and orally (20-40 mg) [3]. Subcutaneous injection is the most studied route. The subcutaneous bioavailability of Hexarelin is about 77% - roughly three quarters of the compound thus reaches the systemic bloodstream directly [3]. Intravenous bolus administration was mainly used for pharmacodynamic tests, while intranasal and oral forms showed significantly lower and more variable bioavailability [3].

In documented gray-market practice outside controlled clinical trials, Hexarelin is mostly injected subcutaneously, usually at 100-200 µg per dose, 1 to 3 times daily on an empty stomach (at least 2-3 hours after the last meal). These protocols lack controlled scientific evidence and are listed here purely descriptively. Commonly described cycle schemes such as "4-8 weeks of use, followed by at least 4 weeks off" are meant to counteract rapid receptor desensitization.

There is no officially approved standard dosage for Hexarelin, as the peptide is not approved as a drug in the EU or the US. For calculating preparation in a research context, the Injection Calculator offers support with reconstitution and determining units.

From vial to use: How do I reconstitute Hexarelin and calculate the dosage?

Hexarelin for research use is typically supplied as a freeze-dried powder (lyophilisate) in vials of 2 mg or 5 mg. Before use, the peptide must be dissolved (reconstituted) with a sterile solvent - standardly with bacteriostatic water (BAC water).

Calculation example for a 5 mg vial of Hexarelin:

• 5 mg Hexarelin dissolved in 2 mL BAC water gives a peptide concentration of 2.5 mg/mL (2,500 µg/mL)
• A target dose of 100 µg Hexarelin equals 0.04 mL (4 insulin units on a U-100 syringe)
• A target dose of 200 µg Hexarelin equals 0.08 mL (8 insulin units on a U-100 syringe)

Calculation example for a 2 mg vial of Hexarelin:

• 2 mg Hexarelin dissolved in 1 mL BAC water gives a peptide concentration of 2 mg/mL (2,000 µg/mL)
• A target dose of 100 µg Hexarelin equals 0.05 mL (5 insulin units on a U-100 syringe)

When reconstituting, let the BAC water run slowly down the inner glass wall of the vial and mix the solution by gentle swirling - avoid vigorous shaking. Store the reconstituted peptide solution refrigerated at 2-8 °C and use it within about 28 days. For detailed handling instructions, see the guides on mixing and storing peptides.

These calculation examples serve solely for harm reduction and information. They do not constitute a medical dosing or usage recommendation.

How does Hexarelin work? Mechanism of action and receptor pathways

Hexarelin acts as a ghrelin mimetic and binds with high affinity to the ghrelin receptor (GHS-R1a) in the hypothalamus and pituitary gland, the central hormonal control center. This receptor binding induces a pulsatile release of growth hormone (GH) and secondarily IGF-1. Hexarelin has about a 30-fold higher binding affinity to the GHS receptor than the precursor peptide GHRP-6, which explains its pronounced potency.

A special feature compared to other GHRPs is Hexarelin's binding to the CD36 receptor on cardiomyocytes. Through this signaling pathway, the peptide mediates cardioprotective effects in ischemia and reperfusion injury to the heart muscle, which have been shown to occur independently of growth hormone secretion [1][2].

As a typical class effect, Hexarelin also stimulates the release of ACTH, cortisol, and prolactin. Compared to more selective agents like Ipamorelin, Hexarelin is therefore considered hormonally less specific, which must be taken into account in pharmacological evaluation.

What do studies show about Hexarelin's effectiveness?

The short-term effectiveness of Hexarelin in raising growth hormone levels is well established in clinical human studies. In the pioneering study by Ghigo et al. (1994), an intravenous dose of 1 µg/kg Hexarelin raised GH levels to about double that of an equivalent dose of GHRH [3]. Subcutaneous injection of 1.5 µg/kg produced a GH response comparable to 1 µg/kg intravenously, supporting the high bioavailability of 77% [3].

The hormonal response to Hexarelin is strongly age-dependent: young subjects show a significantly stronger GH secretion than older people, in whom the hormone increase is measurably smaller.

For lasting effects on muscle building or body composition, scientific evidence is lacking. In a 16-week human study with twice-daily dosing of 1.5 µg/kg SC, pronounced tachyphylaxis (receptor desensitization) was observed: after 2-4 weeks of continuous administration, the GH response drops drastically, making long-term use pharmacologically ineffective.

The protective heart effects of Hexarelin via the CD36 receptor have so far only been demonstrated in animal models and in vitro experiments; clinical human studies on cardioprotection are not available [1][2].

Which dosages of Hexarelin have been studied?

In the clinical studies of the 1990s, the following dosages and routes of administration for Hexarelin were documented [3]:

In the 16-week long-term study, 1.5 µg/kg was given subcutaneously twice daily - corresponding to roughly 100-120 µg per dose at 70 kg body weight. Above doses of 1 µg/kg IV or 1.5 µg/kg SC, a saturation effect in GH release occurs, while side effects on cortisol and prolactin increase.

In non-clinical user reports, dosages of 100-200 µg SC (1-3 times daily) in intervals of 4-8 weeks with several weeks off are often mentioned to reduce desensitization. These schemes come from anecdotal reports and have no regulatory validation.

What side effects and risks does Hexarelin have?

The side effects of Hexarelin documented in scientific studies and user reports include:

• Increase in stress hormones: Rise in prolactin, ACTH, and cortisol due to lack of selectivity compared to Ipamorelin
• Rapid desensitization (tachyphylaxis): Marked loss of GH-releasing effect after 2-4 weeks of continuous use, a known property of the peptide
• Local injection reactions: Temporary burning or redness at the subcutaneous injection site
• Sedation and fatigue: Drowsiness occurring shortly after injection
• Increased appetite: Heightened hunger due to agonism at the ghrelin receptor

The typical misuse is uninterrupted continuous use without cycle breaks, since Hexarelin shows the fastest tachyphylaxis among the GHRP peptides. Criteria for evaluating peptide suppliers and quality markers are provided by the manufacturer-independent Vendor Radar for peptide safety.

What is the legal status of Hexarelin (Examorelin)?

Hexarelin (Examorelin) has no pharmaceutical drug approval either in the European Union (via the EMA) or in the US (FDA). There are no approved medical indications, as clinical development was discontinued after phase II studies in the late 1990s.

Commercially, Hexarelin is primarily sold as a research chemical ("research peptide"). Its use in humans on the gray market occurs without pharmaceutical quality testing and without medical supervision. For further profiles of related GHRP compounds, see the structured peptide library, including the overview of GHRP-6.