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Hexarelin (performance use)

The most potent of the classic GH-releasing hexapeptides, used in performance contexts as much for its CD36-mediated cardiac effects as for the growth hormone spike.

Also known as Examorelin, hexarelin, EP-23905, MF-6003

Human trials — Studied in people, typically early phase or small — promising rather than proven.

Hexarelin's GH-releasing effect in humans is well documented from 1990s pharmacology and endocrine testing studies, including its use as a diagnostic stimulus. Its cardioprotective CD36 activity is solid animal work with only small human cardiac studies behind it, and there is no trial evidence for hypertrophy or athletic performance in healthy adults.

How it works

Hexarelin is a synthetic hexapeptide that activates GHS-R1a in the pituitary and hypothalamus, producing a large pulse of growth hormone - larger than GHRP-6 or ipamorelin at equivalent doses. What sets it apart is a second, GH-independent mechanism: it binds CD36, a scavenger receptor expressed in heart and vascular tissue, and in animal models this produces cardioprotection, improved post-ischaemic function and reduced fibrosis independent of GH release. That effect persists in hypophysectomised animals, which is strong evidence it is real and separate. The practical drawback is that hexarelin desensitises the GHS-R1a receptor faster than any other peptide in its class - GH responses attenuate measurably within about two weeks of continuous dosing - and it raises cortisol and prolactin more than selective agents like ipamorelin.

Targets: GHS-R1a (ghrelin receptor), CD36, Pituitary somatotrophs, Growth hormone / IGF-1 axis

Dosing

ProtocolDoseFrequencyRoute
Standard GH-pulse protocolOn an empty stomach, at least 20 minutes before or two hours after food. One dose before bed is the most common single-dose choice.100 mcgonce to three times dailysubcutaneous
Cardioprotective / low-dose protocolAny time; the CD36 effect is not tied to the GH pulse.50 mcg – 100 mcgonce dailysubcutaneous
  • · 100 mcg is the saturation dose for GH release in most people. Going higher mainly raises cortisol and prolactin without a proportionate GH gain.
  • · Extrapolated from animal cardiac work. There is no human protocol for this use.

Titration

There is little to titrate; 100 mcg saturates the GH response. If you are increasing the dose to chase an effect, you are probably experiencing desensitisation and should take a break instead.

Cycling

Run in short blocks of 2-4 weeks with equal or longer breaks. This is not optional caution - hexarelin desensitises its own receptor faster than any other GHRP, and continuous use past a few weeks progressively stops working.

Work out your exact syringe units →

Pharmacology

Half-life
Roughly 55-70 minutes; the GH pulse it triggers is over well before that.
Onset
GH peaks within 15-30 minutes of injection. Any body-composition effect takes weeks.
Routes
subcutaneous, intramuscular
Molecule
Synthetic hexapeptide GH secretagogue
Sequence length
6 amino acids
Molecular weight
887.04 Da

Handling

Diluent
Bacteriostatic water
Typical mix
2 or 3 mL
Vial sizes
2, 5 mg
Lyophilised
Room temperature is fine short term; fridge or freezer for longer.
Reconstituted
Refrigerated and used within about 30 days.
Light sensitive
Yes — keep it out of the light

Mixing

A 5 mg vial in 2.5 mL gives 2000 mcg/mL, so 100 mcg is 5 units on a U-100 syringe. Aim the stream down the vial wall and swirl.

Side effects

  • very commonIncreased hunger— Ghrelin receptor agonism - less pronounced than GHRP-6 but clearly present.
  • very commonRapid receptor desensitisation— The defining limitation. GH response falls off within roughly two weeks of continuous dosing.
  • commonWater retention and puffiness— Standard GH-mediated effect.
  • commonElevated cortisol and prolactin— More than ipamorelin, less than GHRP-6 at equivalent doses. Sustained prolactin elevation can cause gynaecomastia and libido loss.
  • commonTingling, head rush or flushing after injection— Transient, in the first few minutes.
  • uncommonCarpal tunnel symptoms and joint aches— Dose-related GH effect.
  • uncommonReduced insulin sensitivity— GH is diabetogenic; relevant with sustained use.

Do not use if

  • Active malignancy - raising the GH/IGF-1 axis is not advisable with a proliferative disease present.
  • Prolactinoma or existing hyperprolactinaemia.
  • Poorly controlled diabetes.
  • Pregnancy and breastfeeding.

Combining it

  • synergycjc-1295-no-dac — The standard GHRH-plus-GHRP pairing amplifies the pulse well beyond either alone.
  • redundantipamorelin — Same receptor. Ipamorelin is the cleaner option if cortisol and prolactin matter to you.
  • redundantmk-677 — Both are GHS-R1a agonists; combining them accelerates desensitisation.
  • synergyigf-1-lr3 — Classic stack hitting the GH/IGF axis at two points; also stacks hypoglycaemia and fluid retention risk.

What to monitor

  • · Serum IGF-1 to confirm the axis is actually responding and to detect desensitisation.
  • · Fasting glucose and HbA1c.
  • · Prolactin if you are running it more than a few weeks or notice nipple sensitivity.
  • · Morning cortisol if using high or frequent doses.

Legal status

Not approved for human use in the US or EU; sold as a research chemical. Prohibited at all times in sport by WADA as a growth hormone secretagogue.

References

  • Human GH-response and endocrine studies of hexarelin from the 1990s (trial)
  • Preclinical work on hexarelin, CD36 and cardioprotection independent of growth hormone release (preclinical)
  • Reviews of GH secretagogue receptor desensitisation across the GHRP class (review)

Mechanism in depth

Hexarelin is in the body-composition class rather than the secretagogue class because of what it does outside the pituitary, and that is where the interesting pharmacology sits. At the pituitary it is a GHS-R1a agonist: Gq coupling, phospholipase C, IP3 and diacylglycerol, calcium release from intracellular stores, and GH exocytosis from somatotrophs. It also suppresses somatostatin tone at the hypothalamus, which is why secretagogues in this family amplify the endogenous pulse rather than simply adding to it. Imbimbo's dose-response work in twelve healthy men established the shape of the response precisely: intravenous boluses of 0.5, 1 and 2 mcg/kg produced peak GH of 26.9, 52.3 and 55.0 ng/mL against 3.9 for placebo, with an ED50 of about 0.5 mcg/kg and an Emax of 55.1 ng/mL. The 2 mcg/kg dose sits essentially at the plateau. That is a genuinely useful number: it means the dose-response curve is nearly flat above roughly 2 mcg/kg, which for an 80 kg person is 160 mcg, and everything above that is buying side effects rather than growth hormone. The second half of the mechanism is the part vendors do not mention. Papotti demonstrated GH secretagogue binding sites in peripheral human tissues, and hexarelin in particular binds CD36 in cardiac and vascular tissue - a distinct receptor from GHS-R1a. That is the basis for the cardioprotective effects hexarelin shows in animal models, and it is also why hexarelin has a different peripheral profile from the other GHRPs. Third, and most practically important, is desensitisation. Rahim's study asked directly whether desensitisation to hexarelin occurs, and hexarelin is the GHRP with the most consistent evidence that it does - the GH response attenuates with continued administration in a way that is less pronounced for ipamorelin or GHRP-2. That is the single most useful fact for anyone planning a cycle.

What usually goes wrong

Two things specific to hexarelin. The first is dose escalation past the plateau. Imbimbo's data show the response at 2 mcg/kg is very close to maximal, so the person taking 300 mcg three times daily is getting the same GH as at 100 mcg and considerably more cortisol, prolactin and hunger. The second is running it continuously. Hexarelin is the GHRP with the clearest desensitisation evidence, so the eight-week user whose IGF-1 has drifted back to baseline is not under-dosed, they are desensitised, and increasing the dose makes it worse. Beyond that, the general secretagogue failure modes apply: eating fat or protein within two hours of a dose blunts the pulse through somatostatin, the water retention and carpal tunnel symptoms that appear at weeks two to four are the GH axis working rather than an allergy, and glucose drifts upward on any effective protocol. The cortisol and prolactin elevation is the argument that has moved most experienced users to more selective secretagogues.

Titration ladder

  1. 50 mcgWeek 1 — Subcutaneous, on an empty stomach with no fat or protein for two hours either side, because somatostatin release after a meal blunts the pulse. Watch for the flushing and hunger that indicate the receptor is engaged.
  2. 100 mcgWeeks 2-4 — 100 mcg twice daily is the most commonly used protocol. For an 80 kg person this is around 1.25 mcg/kg, which sits close to Imbimbo's ED50 of 0.5 mcg/kg and well onto the plateau of the curve.
  3. 100 mcgWeeks 5-8, then stop — Do not escalate further. Imbimbo showed the response at 2 mcg/kg is very close to maximal, so more dose buys cortisol and prolactin rather than GH. Because hexarelin desensitises, run 8-12 weeks at most and then take an equal break.

Bloodwork worth running

MarkerWhenWhy it matters
Serum IGF-1Baseline, then at four weeks, and again at eight weeks - the eight-week value is what tells you whether desensitisation has set in.The integrated readout of whether the GH pulses are producing anything. A single GH measurement after a dose is nearly uninterpretable because GH is pulsatile; IGF-1 is not, and it is the marker that tells you whether the axis is actually responding.Act if: An IGF-1 that rose at four weeks and has fallen back toward baseline at eight weeks is desensitisation, and the answer is a break rather than a dose increase. An IGF-1 above the age-adjusted reference range means come down.
Morning cortisol and prolactinBaseline and at four weeks, drawn in the morning at a consistent time.This is hexarelin's specific liability among the secretagogues. It raises ACTH-driven cortisol and prolactin more than the selective agents, and chronically elevated cortisol undoes exactly the body-composition change you are chasing.Act if: A morning cortisol above the reference range, or a prolactin above roughly 20 ng/mL in men, means switch to a more selective secretagogue.
Fasting glucose and HbA1cBaseline and every eight weeks.Growth hormone is a counter-regulatory hormone and raises hepatic glucose output while reducing peripheral insulin sensitivity. Any effective secretagogue moves glycaemia the wrong way.Act if: A fasting glucose above 100 mg/dL that was normal at baseline, or an HbA1c rise above 0.3 percentage points, means reduce the dose or stop.
Free T4 and TSHBaseline and at eight weeks.Growth hormone increases peripheral T4-to-T3 conversion and can unmask marginal thyroid function, which shows as fatigue people misattribute to the peptide not working.Act if: A falling free T4 with a rising TSH needs proper assessment rather than dose escalation.

Pharmacokinetics

Tmax
0.5 h
Crosses blood-brain barrier
partial
Metabolism
Peptidase degradation. The D-amino acid substitutions and C-terminal amidation slow this considerably relative to an all-L linear hexapeptide, which is why hexarelin outlasts GHRP-6.
Elimination
Renal clearance of fragments.

Receptor targets

  • Growth hormone secretagogue receptor 1a (GHS-R1a), the ghrelin receptor — High-affinity agonist; hexarelin is among the more potent peptidic GHS-R1a agonists. Exact Ki not resolved to a primary source here.

    Gq-coupled, PLC-IP3-calcium mediated GH release from somatotrophs, plus suppression of hypothalamic somatostatin tone. Peak GH at 30 minutes, back to baseline by 240 minutes.

  • CD36 (scavenger receptor class B member 3) — Hexarelin binds CD36 in cardiac and vascular tissue - a GHS-R1a-independent target, and the reason hexarelin's peripheral profile differs from other GHRPs

    The basis of the cardioprotective effects seen in animal ischaemia models. Not a GH-mediated effect.

  • Peripheral GH secretagogue binding sites — Demonstrated in human peripheral tissues by Papotti

    Direct tissue effects independent of the GH axis, which is why hexarelin is not simply a GH-release tool.

  • ACTH, cortisol and prolactin axes — Indirect, via GHS-R1a cross-activation

    Hexarelin raises cortisol and prolactin more than the more selective secretagogues such as ipamorelin. This is the main endocrine argument against it for physique use.

What to expect, and when

GH rises within minutes of a dose, peaks at about 30 minutes and is back to baseline within four hours. Flushing, a warm sensation and sharp hunger within ten to twenty minutes are the reliable subjective signs of receptor engagement. IGF-1 rises measurably over two to four weeks. Fluid retention, joint aches and carpal tunnel symptoms appear at weeks two to four if the protocol is working. Desensitisation, where it occurs, shows up as a fading response over roughly six to twelve weeks.

Stacking and comparisons

The standard and mechanistically sound pairing is hexarelin with a GHRH analogue - CJC-1295 or tesamorelin - because they act on different receptors and the combination produces a larger pulse than either alone: the GHRP raises somatotroph responsiveness and suppresses somatostatin, the GHRH analogue provides the releasing signal. The specific caution with hexarelin in that stack is that it desensitises faster than the alternatives, so the GHRP half of the stack is the half that needs cycling. If you want to run a secretagogue continuously, ipamorelin or GHRP-2 are the better choices and the reason is receptor kinetics, not marketing. Stacking hexarelin with anything that raises prolactin - and it raises prolactin itself - compounds a problem that presents as low libido and gets blamed on everything else. Combining with beta-adrenergic agents has been studied directly by Arvat, which is worth knowing if clenbuterol is in the plan. The pairing with insulin or IGF-1 analogues carries the usual counter-regulatory tension: GH raises glucose, IGF-1 lowers it, and the net effect on any given day is unpredictable.

Against ipamorelin: ipamorelin is the selective one, raising GH with minimal effect on cortisol and prolactin, and it does not desensitise as readily. Hexarelin produces a larger GH pulse and pays for it endocrinologically. If you are running a secretagogue for months, ipamorelin is the better tool; if you want the biggest single pulse for a defined eight-week block, hexarelin is defensible. Against GHRP-6, hexarelin is the 2-methylated derivative with greater potency and less of the extreme hunger. Against tesamorelin, which is also in this class: tesamorelin is a GHRH analogue with phase 3 data in over 800 patients showing measurable visceral fat reduction, while hexarelin has a good dose-response study from 1994 and nothing resembling an outcome trial. Against direct growth hormone, secretagogues preserve pulsatility and the negative feedback loop, which is a genuine physiological advantage, but they cannot exceed what your pituitary is capable of releasing - and Imbimbo's Emax of 55 ng/mL is that ceiling made visible.

Rough cost

$40–$120/month. 5 mg vials commonly 30-70 USD grey market, and 100 mcg twice daily consumes 6 mg a month. Cheap relative to almost anything else in this class, which is much of its appeal.

Genuinely uncertain

  • No pharmacokinetic study of the hexarelin peptide itself was resolved - the 55-minute half-life figure describes the decay of the GH response, not the peptide's plasma concentration.
  • Subcutaneous bioavailability has not been quantified; the human dose-response work used the intravenous route.
  • The GHS-R1a binding affinity of hexarelin was not resolved to a primary source in this session.
  • The timescale over which desensitisation develops, and how completely it reverses with a break, are not well quantified.
  • Whether the CD36-mediated cardiac effects seen in animal models occur at the doses people use subcutaneously is unknown.
  • There is no human study of hexarelin for body composition. The GH and IGF-1 responses are documented; the downstream physique effect is not.
  • The magnitude of cortisol and prolactin elevation at commonly used subcutaneous doses, as opposed to the intravenous doses used in the endocrine studies, is not well characterised.

Papers