Overview
Hexarelin is a synthetic 6-amino-acid growth hormone-releasing peptide developed in the 1990s by Italian groups around Bowers and Ghigo. On a per-microgram basis it is the most potent acute GH-releaser of the classic GHRPs, with consistent dose–response data in healthy adults, older adults, and several disease states. Two clinical wrinkles separate it from ipamorelin and GHRP-6: a more pronounced cortisol and prolactin spike, and notable receptor desensitization (tachyphylaxis) when dosed daily for more than a couple of weeks. There is also a small but interesting body of cardiac-tissue work — hexarelin and ghrelin-pathway agonists may have cardioprotective effects independent of GH release — but human cardiac-outcome trials have not been completed.
Mechanism
Agonist at the growth hormone secretagogue receptor (GHSR-1a) at the pituitary and hypothalamus, driving pulsatile GH release. Synergizes with GHRH and GHRH analogs (CJC-1295). Independent binding to a separate cardiac receptor (CD36) has been described and underpins the proposed cardioprotective effects in animal myocardium. Sustained daily exposure downregulates GHSR-1a signaling, attenuating GH response within ~2–3 weeks of continuous dosing.
Evidence by indication
We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.
Stimulation of endogenous GH release
Multiple human pharmacology studies (Imbimbo 1994, Ghigo 1994, Massoud 1996) consistently demonstrate acute GH release after SubQ or IV administration, with hexarelin showing the largest acute peak among the classic GHRPs at equivalent doses. Tier 2 because the indication is biochemical and the studies are short-duration, small-cohort.
Cardioprotection / post-MI cardiac function
Animal myocardium and isolated-heart preparations show hexarelin attenuates ischemia-reperfusion injury, possibly via CD36 binding independent of GH release. Small early-phase human studies in chronic heart failure exist but are underpowered for clinical outcomes; no large trial has been completed.
Body composition / fat loss / muscle gain
Mechanism-as-evidence reasoning from acute GH release. No directly designed RCT in healthy adults using body composition or strength as a primary endpoint. Confounded by tachyphylaxis.
No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.
Studied dose ranges
The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.
Community standard is 100 mcg per dose 1–2× daily, cycled (e.g., 4–6 weeks on / 4 weeks off) to mitigate tachyphylaxis. Doses above ~200 mcg produce diminishing returns on GH while increasing cortisol/prolactin spikes.
Contraindications
- Active malignancy (theoretical concern from GH/IGF-1 elevation)
- Uncontrolled diabetes (insulin resistance worsens with sustained GH spikes)
- Pregnancy and breastfeeding
- Adolescents with open growth plates (use only under endocrinology supervision)
- Significant baseline cortisol elevation (Cushing's, chronic prednisone) — hexarelin further raises cortisol
- Known hypersensitivity to peptide formulations
Reported side effects
- Cortisol and prolactin elevation — more pronounced than ipamorelin, similar to or greater than GHRP-6
- Mild appetite stimulation (less than GHRP-6, more than ipamorelin)
- Lethargy, transient flushing, or sweating shortly after injection
- Tachyphylaxis: GH response attenuates with continuous daily dosing beyond ~2–3 weeks
- Water retention, mild puffiness
- Numbness or tingling with chronic high-dose use (consistent with the IGF-1 carpal-tunnel-like syndrome of GH excess)
Reconstitution & storage
Lyophilized powder reconstituted with bacteriostatic water. A 5 mg vial in 2.5 mL BAC water = 2 mg/mL, making a 100 mcg dose = 5 units on a U-100 syringe. Use the Juno calculator to verify any specific vial size.
Storage. Lyophilized: refrigerate 2–8 °C. Reconstituted: refrigerate 2–8 °C, use within 30 days.
Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.
Editorial note
DRAFT — pending Wayne's review. Hexarelin is the 'most potent on paper' GHRP but the cortisol/prolactin and tachyphylaxis profile makes it a poor daily-driver compared to ipamorelin or MK-677. The cardioprotective story is real preclinically but unconverted to human clinical outcomes — keep that framing honest.
Citations
- [1]Pharmacokinetics and pharmacodynamics of hexarelin, a new growth hormone-releasing peptide, after intravenous, subcutaneous, intranasal, and oral administration in manImbimbo BP, Mant T, Edwards M, et al. · European Journal of Clinical Pharmacology · 1994 · PMID 8200953Foundational human PK/PD characterization of hexarelin across IV/SubQ/intranasal/oral; anchors the SubQ dose range and routes.View source
- [2]The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivenessMassoud AF, Hindmarsh PC, Brook CG. · Clinical Endocrinology · 1996 · PMID 8772586Human study characterizing tachyphylaxis with repeated dosing — direct evidence that daily continuous dosing attenuates GH response.View source
- [3]Effects of hexarelin on the cardiovascular system: a reviewBroglio F, Benso A, Gottero C, et al. · Cardiovascular Drug Reviews · 2002 · PMID 12466369Cross-trial review of hexarelin cardiovascular effects, including the GH-independent CD36-mediated cardiac actions; anchors Tier 3 cardioprotection.View source