Hexarelin: Growth Hormone Release, Dosage & Side Effects

What Is Hexarelin?

Hexarelin (also known as Examorelin) is a synthetic hexapeptide growth hormone secretagogue that stimulates GH release from the anterior pituitary gland. Discovered in the early 1990s by researchers in Italy, hexarelin binds to the growth hormone secretagogue receptor (GHS-R1a) — the same ghrelin receptor that ipamorelin and GHRP-6 target — but with notably higher potency than most compounds in its class.

Its amino acid sequence (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) was specifically engineered for oral stability and high receptor binding affinity. Among all synthetic GH secretagogues studied in humans, hexarelin consistently produces the largest acute GH release, making it a valuable research tool for understanding somatotroph function and GH axis physiology.

For context on how hexarelin fits within the broader peptide landscape, see our hexarelin compound page and our guide on peptides for muscle growth.

How Hexarelin Stimulates Growth Hormone Release

Hexarelin works through a mechanism that is both complementary to and distinct from natural GHRH signaling. Understanding this mechanism explains both its potency and its limitations.

GHS-R1a Receptor Activation. Hexarelin binds to the growth hormone secretagogue receptor type 1a (GHS-R1a) on pituitary somatotroph cells. This receptor is a G protein-coupled receptor that, when activated, triggers intracellular calcium mobilization and subsequent GH vesicle exocytosis. Hexarelin's binding affinity for GHS-R1a is among the highest of any synthetic peptide tested.

Synergy With Endogenous GHRH. GH secretion is controlled by two opposing signals: GHRH (stimulatory) and somatostatin (inhibitory). Hexarelin amplifies GH release most effectively when endogenous GHRH is present, because it works through a different intracellular pathway (phospholipase C) than GHRH (cAMP). This is why researchers often pair ghrelin-receptor agonists with GHRH analogs like CJC-1295 — the combination targets two distinct signaling cascades simultaneously.

The Cortisol and Prolactin Question. Unlike ipamorelin, which selectively releases GH without meaningfully affecting cortisol or prolactin, hexarelin does produce dose-dependent increases in cortisol, prolactin, and ACTH. This is an important distinction. At standard research doses (1-2 mcg/kg), these elevations are generally transient and clinically modest. At higher doses, however, cortisol and prolactin increases become more pronounced.

Cardioprotective Signaling. One of hexarelin's most distinctive properties is its activity at cardiac receptors. Research by Bhatt and colleagues demonstrated that hexarelin binds to a specific receptor on cardiac cells (CD36) that is distinct from GHS-R1a. This binding appears to mediate cardioprotective effects that are independent of growth hormone release — a unique property among GH secretagogues.

What the Clinical Research Shows

Hexarelin has been tested in human clinical trials more extensively than many GH secretagogues, though it never achieved regulatory approval as a therapeutic agent.

Acute GH Release Studies. Multiple clinical studies confirm that hexarelin produces the largest acute GH spike among tested secretagogues. Ghigo et al. (1994) demonstrated that a single subcutaneous injection of hexarelin at 1 mcg/kg produced mean peak GH levels of approximately 50-80 ng/mL in healthy young men — substantially higher than equivalent doses of GHRP-6 or GHRP-2. In elderly subjects, the GH response was reduced but still significant, suggesting that hexarelin partially overcomes age-related somatopause.

The Desensitization Problem. The most significant finding from chronic hexarelin research is rapid receptor desensitization. Rahim et al. (1998) showed that continuous administration of hexarelin for 16 weeks resulted in progressive attenuation of the GH response. By week 4, peak GH levels had already declined substantially compared to the initial response. By week 16, the GH-releasing effect was markedly blunted. This desensitization is one of the primary reasons hexarelin did not advance to approval — sustained GH elevation requires cycling strategies rather than continuous use.

Cardioprotection in Humans. Bisi et al. and subsequent investigators explored hexarelin's cardiac effects. In patients with GH deficiency, hexarelin improved cardiac performance parameters (ejection fraction, cardiac output) through mechanisms that appeared partially independent of GH elevation. This line of research, while promising, was not pursued to phase 3 due to the desensitization issue affecting the GH pathway.

Comparison to Other Secretagogues. In head-to-head studies, hexarelin consistently produces higher peak GH than GHRP-6, GHRP-2, or ipamorelin at equivalent weight-based doses. However, it also produces more off-target hormonal effects. This creates a clear trade-off: maximal GH release versus selectivity. For a comparison of secretagogue selectivity, see our ipamorelin safety analysis.

Hexarelin Dosage Protocols

Research protocols for hexarelin typically use weight-based dosing. The following ranges are derived from published clinical studies. For general peptide dosing principles, see our Peptide Dosage Guide.

Timing. GH secretion follows a natural pulsatile pattern. Most researchers administer hexarelin on an empty stomach, as food intake (especially fats and carbohydrates) can blunt the GH response. The most common timing is morning (fasted) and pre-bed, with an optional post-exercise dose. Allow at least 2 hours after eating before administration.

Cycling Is Mandatory. Due to the well-documented desensitization phenomenon, hexarelin should not be used continuously. Typical cycling protocols involve 4-8 weeks of use followed by an off period of at least 4 weeks. Some researchers alternate between hexarelin and other secretagogues (like ipamorelin, which shows less desensitization) during off cycles.

For guidance on reconstitution and injection technique, see How to Reconstitute Peptides and How to Inject Peptides.

Side Effects and Safety Considerations

Hexarelin's side effect profile reflects its broader hormonal activity compared to more selective secretagogues.

Common side effects (reported in clinical trials):

• Transient cortisol elevation — Dose-dependent; generally returns to baseline within 2-4 hours. More pronounced at doses above 2 mcg/kg.
• Prolactin increase — Typically mild and transient at standard doses. Chronic elevation could theoretically affect libido or cause gynecomastia, reinforcing the importance of cycling.
• Increased hunger — Ghrelin receptor activation stimulates appetite. This can be beneficial for individuals seeking caloric surplus or problematic for those managing weight.
• Water retention — As with all GH-elevating compounds, some fluid retention is possible, particularly during the initial phase of use.
• Injection site reactions — Mild redness or irritation at the injection site, consistent with other subcutaneous peptides.
• Headache and flushing — Reported occasionally, usually resolving with continued use.

The desensitization issue is the most practically important "side effect." It is not harmful per se, but it means the compound stops working as intended if used continuously. This is not merely theoretical — it is clearly documented in 16-week clinical data.

Hexarelin vs Other GH Secretagogues

The key takeaway: hexarelin delivers the highest peak GH release but at the cost of broader hormonal effects and faster desensitization. Ipamorelin offers cleaner, more selective stimulation with less desensitization — making it better suited for longer protocols. For most users, the CJC-1295 + Ipamorelin stack provides a more sustainable approach to GH optimization than hexarelin alone.

Who Should Consider Hexarelin

Hexarelin occupies a specific niche in the GH secretagogue landscape:

• Short-term GH pulse protocols — Researchers looking for maximal acute GH release in cycled protocols (4-8 weeks) may prefer hexarelin over more moderate secretagogues.
• Cardiac research applications — The unique CD36-mediated cardioprotective signaling makes hexarelin of interest for cardiovascular research, independent of its GH effects.
• GH axis assessment — Clinically, hexarelin has been used as a diagnostic tool to assess pituitary GH reserve, as its potent stimulation helps differentiate between pituitary and hypothalamic causes of GH deficiency.
• Rotation strategies — Some researchers incorporate hexarelin into rotating protocols, using it during "on" cycles and switching to ipamorelin or CJC-1295 during periods when hexarelin sensitivity is being restored.

For individuals seeking sustained, long-term GH optimization with fewer side effects, ipamorelin or the CJC-1295/Ipamorelin combination remains the better-studied and more practical option. See our anti-aging goals page for the broader context of GH peptides in longevity research.