Hexarelin

Hexarelin is a synthetic growth hormone-releasing peptide (GHRP) that stimulates the pituitary gland to release growth hormone (GH) through activation of the ghrelin receptor (GHSR-1a) and the cardiac-specific CD36 receptor. Its primary human-use benefits include enhanced GH secretion, improved cardiac function, reduced body fat, increased lean muscle mass, and cardioprotective effects. Hexarelin is popular among bodybuilders, athletes, anti-aging enthusiasts, and individuals seeking to optimize body composition and recovery. Typical dosages range from 100–300 mcg administered subcutaneously 1–3 times daily, with cycling protocols generally spanning 8–12 weeks followed by an off period to prevent receptor desensitization.

What Is Hexarelin?

Hexarelin (also known by its International Nonproprietary Name, Examorelin) is a synthetic hexapeptide composed of six amino acids with the sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter> Developed in the 1990s, it belongs to the growth hormone secretagogue (GHS) class of compounds designed to stimulate endogenous growth hormone release from the anterior pituitary gland.

What distinguishes hexarelin from other GHRPs is its exceptional potency and chemical stability. Research demonstrates that hexarelin produces a substantial and dose-dependent increase in growth hormone levels in humans, with effects observed across multiple administration routes including intravenous, subcutaneous, intranasal, and even oral delivery.<parameter name="url">https://academic.oup.com/jcem/article-abstract/83/5/1644/2865542</parameter> Unlike its natural counterpart ghrelin, which has a half-life of only 11–31 minutes, hexarelin maintains a significantly longer half-life of 57–71 minutes, making it more practical for therapeutic applications.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter>

The primary benefits that draw users to hexarelin include:

• Potent stimulation of growth hormone release
• Cardioprotective effects independent of GH elevation
• Enhanced fat metabolism and body composition
• Improved muscle recovery and lean mass development
• Anti-fibrotic and anti-apoptotic properties in cardiac tissue

How It Works

GHSR-1a Receptor Activation

Hexarelin exerts its primary GH-releasing effects through binding to the growth hormone secretagogue receptor type 1a (GHSR-1a), a G protein-coupled receptor located in the hypothalamus and pituitary gland.<parameter name="url">https://www.sciencedirect.com/topics/neuroscience/hexarelin</parameter> Upon binding, hexarelin activates the phospholipase C pathway, leading to increased intracellular calcium and subsequent GH release from somatotroph cells. The half-maximal effective concentration (EC50) of hexarelin for GHSR-1a is approximately 1.7 nmol/L, comparable to the natural ligand ghrelin at 1.0 nmol/L.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter>

CD36 Cardiac Receptor Pathway

A unique feature of hexarelin is its ability to activate the CD36 receptor, a multifunctional glycoprotein expressed in cardiomyocytes and microvascular endothelial cells. This receptor mediates hexarelin's cardioprotective effects independently of growth hormone release.<parameter name="url">https://www.ahajournals.org/doi/10.1161/01.RES.85.9.796</parameter> Studies using CD36-null mice confirmed that hexarelin's cardiovascular actions are largely mediated through this receptor, explaining why hexarelin demonstrates more potent cardiac benefits than ghrelin despite similar GHSR-1a affinity.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter>

Hypothalamic-Pituitary Axis Modulation

Hexarelin influences the hypothalamic-pituitary axis through both direct pituitary stimulation and hypothalamic modulation. Research indicates that hexarelin's mechanism involves interaction with growth hormone-releasing hormone (GHRH) pathways and suppression of somatostatin, the GH-inhibiting hormone.<parameter name="url">https://www.researchgate.net/publication/15466686_Mechanism_of_Action_of_Hexarelin_and_GHRP-6_Analysis_of_the_Involvement_of_GHRH_AND_Somatostatin_in_the_Rat</parameter> This dual action produces more robust GH pulses than either pathway alone.

Cardioprotective Mechanisms

Hexarelin demonstrates multiple cardioprotective mechanisms including inhibition of cardiomyocyte apoptosis, reduction of cardiac fibrosis, and protection against ischemia-reperfusion injury. In spontaneously hypertensive rats, hexarelin treatment significantly reduced cardiac fibrosis by decreasing interstitial and perivascular myocardial collagen deposition.<parameter name="url">https://journals.physiology.org/doi/10.1152/ajpheart.00257.2011</parameter> These effects occur through modulation of matrix metalloproteinases and suppression of transforming growth factor-β signaling.

Dosage Protocols

Hexarelin dosing in research and clinical settings typically follows these parameters:

Standard dosing: 100–200 mcg per injection, administered 1–3 times daily

Clinical research dosing: Studies have utilized 2 mcg/kg intravenously for acute cardiac effects, while chronic administration protocols have employed 100–200 mcg/kg per day subcutaneously.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter>

Cycling considerations: Due to the potential for receptor desensitization with prolonged use, cycling protocols are commonly recommended. Research has demonstrated that chronic hexarelin therapy results in partial and reversible attenuation of the GH response.<parameter name="url">https://academic.oup.com/jcem/article-abstract/83/5/1644/2865542</parameter> A typical approach involves 8–12 weeks of use followed by 4–8 weeks off to allow receptor sensitivity to recover.

Timing: Administration on an empty stomach, typically 30–60 minutes before meals or before sleep, optimizes GH release. Some protocols suggest splitting doses between morning and evening to mimic natural GH pulsatility.

How to Use / Administration

Hexarelin is most commonly administered via subcutaneous injection, though research has explored multiple routes:

Subcutaneous injection: The preferred method for most users. Inject into fatty tissue areas such as the abdomen, thigh, or upper arm. Rotate injection sites to prevent lipodystrophy.

Intravenous administration: Used primarily in clinical research settings, IV administration produces rapid onset of effects but requires medical supervision.

Intranasal delivery: Studies have demonstrated GH-releasing activity through intranasal administration, though bioavailability is lower than injectable routes.

Oral administration: Hexarelin retains some activity when taken orally, a unique characteristic among GHRPs. One study demonstrated that a single oral dose of hexarelin protected chronic cardiac function after acute myocardial infarction.<parameter name="url">https://pubmed.ncbi.nlm.nih.gov/24747279/</parameter>

For subcutaneous administration, standard injection technique applies: clean the injection site with alcohol, pinch the skin, insert the needle at a 45–90 degree angle, inject slowly, and apply gentle pressure after withdrawal.

Results Timelines

Acute effects (within hours): GH elevation occurs within 15–30 minutes of administration, peaking at approximately 30 minutes and lasting up to 60 minutes. Acute inotropic effects on cardiac function have been observed within this timeframe in clinical studies.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter>

Short-term (1–4 weeks): Users may notice improved sleep quality, enhanced recovery from exercise, and initial changes in body composition. Increased appetite is common during this phase.

Medium-term (4–8 weeks): More noticeable improvements in lean muscle mass, fat reduction, and exercise capacity typically emerge. Skin quality improvements and enhanced recovery become more apparent.

Long-term (8–12+ weeks): Maximum benefits in body composition, strength gains, and metabolic improvements are generally achieved. However, GH response may begin to attenuate, supporting the rationale for cycling.

Research Evidence

Hexarelin has been extensively studied in both animal models and human clinical trials:

Growth hormone release: A double-blind, placebo-controlled study evaluated hexarelin's GH-releasing activity in healthy human subjects, demonstrating substantial and dose-dependent increases in growth hormone levels.<parameter name="url">https://pubmed.ncbi.nlm.nih.gov/7957536/</parameter>

Cardiac function: In 24 patients with coronary artery disease undergoing bypass surgery, acute hexarelin administration (2 mcg/kg IV) increased left ventricular ejection fraction (LVEF), cardiac output, and cardiac index while reducing wedge pressure.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter>

Cardioprotection: Hexarelin treatment preserved myocardial function and reduced infarct size in mouse models of myocardial infarction.<parameter name="url">https://physoc.onlinelibrary.wiley.com/doi/abs/10.14814/phy2.13699</parameter> The peptide significantly reduced cardiac fibrosis in spontaneously hypertensive rats by decreasing collagen deposition and modulating matrix metalloproteinase activity.<parameter name="url">https://journals.physiology.org/doi/10.1152/ajpheart.00257.2011</parameter>

Metabolic effects: Research in diabetic mouse models showed that hexarelin treatment significantly improved glucose and insulin intolerance and decreased plasma and liver triglycerides.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC5659698/</parameter>

GH-independent effects: Studies in hypophysectomized rats and GH-deficient patients confirmed that hexarelin's cardioprotective effects occur independently of growth hormone elevation, mediated primarily through CD36 receptor activation.<parameter name="url">https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/</parameter>

Stacking

Hexarelin is frequently combined with other peptides to enhance overall effects:

Hexarelin + CJC-1295: This combination pairs hexarelin's acute GH pulse with CJC-1295's extended GH-releasing hormone activity, producing synergistic, multi-phase GH elevation. CJC-1295 extends the duration of GH secretion while hexarelin triggers the initial release.

Hexarelin + GHRH analogs: Combining hexarelin with growth hormone-releasing hormone analogs (such as Sermorelin or Modified GRF 1-29) amplifies GH release beyond what either compound achieves alone, as they work through complementary pathways.

Hexarelin + Ipamorelin: While both are GHRPs, ipamorelin is more selective for GH release with minimal effects on cortisol and prolactin. Some users alternate between the two or use lower doses of each to balance potency with selectivity.<parameter name="url">https://medisearch.io/blog/hexarelin-vs-ipamorelin</parameter>

When stacking, dosages of individual compounds are typically reduced to account for synergistic effects and minimize potential side effects.

Reconstitution, Storage & Prep

Hexarelin is supplied as a lyophilized (freeze-dried) powder requiring reconstitution before use:

Reconstitution: Add bacteriostatic water (BAC water) to the vial containing the lyophilized powder. Direct the stream of water against the vial wall rather than directly onto the powder to prevent degradation. Allow the powder to dissolve naturally without shaking—gentle swirling is acceptable if needed.

Typical reconstitution volumes: For a 5mg vial, adding 2.5ml of BAC water yields a concentration of 2mg/ml (200mcg per 0.1ml). Adjust volumes based on desired concentration and ease of dosing.

Storage:

• Unreconstituted powder: Store at room temperature or refrigerated; stable for extended periods
• Reconstituted solution: Refrigerate at 2–8°C (36–46°F); use within 4–6 weeks
• Avoid freezing reconstituted peptide
• Protect from light and heat

Preparation tips: Use insulin syringes (typically 29–31 gauge) for accurate dosing and comfortable injection. Always use sterile technique when drawing from vials.

Side Effects

Hexarelin is generally well-tolerated at therapeutic doses, but potential side effects include:

Common side effects:

• Injection site reactions (redness, mild tenderness)
• Temporary fatigue or lethargy
• Increased appetite
• Water retention or mild bloating
• Headache

Less common side effects:

• Elevated cortisol levels (dose-dependent)
• Increased prolactin levels
• Joint pain or stiffness
• Numbness or tingling in extremities

Dose-dependent concerns: Research has demonstrated that high doses of hexarelin can increase serum cortisol levels.<parameter name="url">https://www.peptides.org/hexarelin-side-effects/</parameter> This effect is more pronounced with hexarelin than with more selective GHRPs like ipamorelin.

Desensitization: Prolonged continuous use may lead to receptor desensitization and reduced GH response, which is reversible upon discontinuation.<parameter name="url">https://academic.oup.com/jcem/article-abstract/83/5/1644/2865542</parameter>

No serious adverse events have been reported at therapeutic doses in clinical studies, and hexarelin demonstrates an excellent safety profile across multiple research investigations.<parameter name="url">https://www.paragonsportsmedicine.com/peptides/hexarelin</parameter>

Legal Status / FDA

Hexarelin is not approved by the United States Food and Drug Administration (FDA) for human use.<parameter name="url">https://www.peptides.org/hexarelin/</parameter> In the United States, it is legal to purchase for research purposes only and cannot be marketed or prescribed for therapeutic use in humans.

The regulatory landscape varies internationally:

• United States: Not FDA-approved; legal for research only
• European Union: Not approved for clinical use; available for research
• Other regions: Regulations vary; may require prescription or be completely restricted

Hexarelin falls into a regulatory gray area common to many research peptides. While not explicitly illegal to possess in most jurisdictions, its sale for human consumption is prohibited. Compounding pharmacies in some regions may prepare hexarelin under physician supervision, though this practice exists in a complex regulatory environment.

Sports/WADA

Hexarelin is explicitly prohibited in competitive sports. The World Anti-Doping Agency (WADA) includes hexarelin (listed under its INN name Examorelin) on the Prohibited List under Section S2: Peptide Hormones, Growth Factors, Related Substances, and Mimetics.<parameter name="url">https://kamu.suek.fi/en/dopingsubstances/

The substance is banned at all times, both in-competition and out-of-competition, due to its growth hormone-releasing properties. Athletes subject to anti-doping regulations should be aware that:

• Hexarelin is detectable through standard anti-doping testing
• Use constitutes a doping violation regardless of therapeutic intent
• No Therapeutic Use Exemption (TUE) is typically granted for GHRPs
• Penalties for positive tests can include multi-year suspensions

The UK Anti-Doping agency confirmed that Examorelin (hexarelin) was added to the prohibited list with its International Nonproprietary Name to ensure clarity in enforcement.<parameter name="url">https://www.ukad.org.uk/summary-major-changes-2019-prohibited-list</parameter>

Conclusion

Hexarelin represents one of the most potent and well-researched growth hormone-releasing peptides available. Its dual mechanism of action through both GHSR-1a and CD36 receptors provides unique benefits, particularly regarding cardiovascular protection that extends beyond simple GH elevation. The extensive body of peer-reviewed research supporting its efficacy in stimulating growth hormone release, improving cardiac function, and providing cardioprotective effects makes it a compound of significant interest.

However, users must understand that hexarelin remains unapproved for human therapeutic use by regulatory agencies worldwide. Those choosing to use hexarelin should do so with full awareness of its legal status, potential side effects, and the importance of proper cycling to maintain receptor sensitivity. The compound's prohibition in competitive sports further limits its applicability for athletes subject to anti-doping regulations.

For individuals seeking to optimize growth hormone levels and potentially benefit from hexarelin's cardioprotective properties, consultation with a knowledgeable healthcare provider is advisable to weigh individual risks and benefits.

FAQ

What is the difference between hexarelin and ipamorelin?
Both are growth hormone-releasing peptides, but hexarelin is more potent and has broader hormone-releasing activity, affecting cortisol and prolactin levels in addition to GH. Ipamorelin is more selective for GH release with minimal impact on other hormones, making it a gentler option with fewer potential side effects.

How quickly does hexarelin work?
GH elevation begins within 15–30 minutes of administration, peaks at approximately 30 minutes, and effects last up to 60 minutes. Noticeable changes in body composition and recovery typically require several weeks of consistent use.

Can hexarelin be taken orally?
Yes, hexarelin retains some activity when taken orally, which is unusual among peptides. However, bioavailability is significantly lower than injectable routes, requiring higher doses for comparable effects.

Does hexarelin cause water retention?
Mild water retention is a common side effect, particularly during initial use. This typically subsides as the body adjusts and can be managed through adequate hydration and monitoring sodium intake.

How long should I cycle hexarelin?
Most protocols recommend 8–12 weeks of use followed by 4–8 weeks off. This cycling approach helps prevent receptor desensitization and maintains the peptide's effectiveness over time.

Is hexarelin safe for long-term use?
Clinical studies have not identified serious adverse events at therapeutic doses. However, chronic use may lead to partial attenuation of GH response, supporting the rationale for cycling. Long-term safety data in humans remains limited.

Can hexarelin be used for anti-aging purposes?
Many users employ hexarelin for its potential anti-aging benefits related to GH optimization, including improved skin quality, body composition, and recovery. However, these applications remain off-label and unapproved.

What time of day is best to take hexarelin?
Administration on an empty stomach optimizes absorption. Many users prefer dosing before bed to complement natural nocturnal GH release, though morning dosing or split doses are also common approaches.

References

1. Mao Y, Tokudome T, Kishimoto I. The cardiovascular action of hexarelin. J Geriatr Cardiol. 2014;11(3):253-258. https://pmc.ncbi.nlm.nih.gov/articles/PMC4178518/
2. Rahim A, O'Neill PA, Shalet SM. Growth hormone status during long-term hexarelin therapy. J Clin Endocrinol Metab. 1998;83(5):1644-1649. https://academic.oup.com/jcem/article-abstract/83/5/1644/2865542
3. Ghigo E, et al. Growth hormone-releasing activity of hexarelin in humans. J Clin Endocrinol Metab. 1994;79(4):940-945. https://pubmed.ncbi.nlm.nih.gov/7957536/
4. Xu X, et al. Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2012;303(6):H703-H711. https://journals.physiology.org/doi/10.1152/ajpheart.00257.2011
5. Bodart V, et al. Identification and characterization of a new growth hormone-releasing peptide receptor in the heart. Circ Res. 1999;85(9):796-802. https://www.ahajournals.org/doi/10.1161/01.RES.85.9.796
6. Ma Y, et al. Hexarelin, a Growth Hormone Secretagogue, Improves Lipid Metabolic Abnormalities in Diabetic Mice. Int J Mol Sci. 2017;18(10):2067. https://pmc.ncbi.nlm.nih.gov/articles/PMC5659698/
7. Bresciani E, et al. Hexarelin targets neuroinflammatory pathways to preserve cardiac morphology and function. Biomed Pharmacother. 2020;127:110165. https://www.sciencedirect.com/science/article/pii/S0753332220303577
8. Hexarelin - ScienceDirect Topics. https://www.sciencedirect.com/topics/neuroscience/hexarelin
9. WADA Prohibited List 2025. World Anti-Doping Agency. https://www.wada-ama.org/en/prohibited-list
10. UK Anti-Doping. Summary of Major Changes to the 2019 Prohibited List. https://www.ukad.org.uk/summary-major-changes-2019-prohibited-list
11. Peptides.org. Hexarelin Reviews, Clinical Trials, and Safety. https://www.peptides.org/hexarelin/
12. Tivesten A, et al. The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction. Endocrinology. 2000;141(1):60-66. https://academic.oup.com/endo/article/141/1/60/2987850