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Ghrelin

The endogenous 28-amino-acid stomach hormone that every GHRP in this class is imitating, used almost exclusively as a research tool because its short half-life and octanoyl modification make it impractical as a drug.

Also known as Acyl-ghrelin, Lenomorelin, The hunger hormone, Octanoylated ghrelin

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

Ghrelin's physiology in humans is extremely well characterised through infusion studies covering GH release, appetite, gastric motility, cardiac output and energy balance. What does not exist is any evidence that injecting it is a sensible way to achieve anything, given a half-life measured in minutes and an acyl group that hydrolyses in solution - the synthetic mimetics exist precisely to solve that problem.

How it works

Ghrelin is produced mainly by X/A-like cells of the gastric fundus and is the only known peripherally produced orexigenic hormone. Its biological activity requires n-octanoylation of serine-3 by ghrelin O-acyltransferase; the des-acyl form circulates at higher concentrations but does not activate GHS-R1a and appears to have separate, partly opposing metabolic actions. Acyl-ghrelin binds GHS-R1a in the pituitary to release GH, in the arcuate nucleus to activate NPY/AgRP neurons and drive food intake, and in the gut and vagus to accelerate gastric emptying. It also has documented cardiovascular effects including improved cardiac output and reduced systemic vascular resistance, plus anti-inflammatory effects on IL-6 and TNF-alpha. Circulating levels rise before meals and fall after eating, and are chronically low in obesity and high in anorexia and cachexia.

Targets: GHS-R1a (ghrelin receptor), Arcuate NPY/AgRP neurons, Vagal afferents, Pituitary somatotrophs, Cardiac tissue

Dosing

ProtocolDoseFrequencyRoute
Research intravenous bolusIn a supervised research setting with serial GH and appetite measurement.—single dose or short infusionintravenous
  • · Human studies have used bolus doses of roughly 1 mcg/kg intravenously, or continuous infusions in the region of 5 pmol/kg/min. For a 70 kg adult a bolus is therefore around 70 mcg. There is no therapeutic protocol.

Cycling

Not used as a therapy and therefore not cycled. Its half-life makes any chronic protocol impractical - the entire GHRP class exists because ghrelin itself cannot be dosed usefully.

Work out your exact syringe units →

Pharmacology

Half-life
Very short - roughly 10 to 30 minutes for the active acylated form, which is why it has never become a practical therapeutic.
Onset
GH and hunger both rise within 15 to 30 minutes of intravenous administration.
Routes
intravenous, subcutaneous
Molecule
Endogenous 28-amino-acid peptide hormone with an n-octanoyl modification at Ser3
Sequence length
28 amino acids
Molecular weight
3370.9 Da

Handling

Diluent
Bacteriostatic water or sterile saline for research use
Typical mix
1 or 2 mL
Vial sizes
1 mg
Lyophilised
Freeze at minus 20 degrees C or below for anything beyond short-term.
Reconstituted
Refrigerated and used within days, not weeks.
Light sensitive
Yes — keep it out of the light

Mixing

The octanoyl ester at Ser3 is hydrolytically labile, so reconstituted acyl-ghrelin loses activity considerably faster than a plain peptide. Grey-market 'ghrelin' is frequently des-acyl and therefore inert at GHS-R1a.

Side effects

  • very commonIntense hunger— The most consistent effect in human infusion studies.
  • commonFlushing and warmth
  • commonTransient drop in blood pressure— Ghrelin reduces systemic vascular resistance; relevant with intravenous bolus dosing.
  • uncommonSweating
  • uncommonElevated prolactin and cortisol— Modest compared with the synthetic GHRPs.
  • uncommonIncreased fasting glucose and reduced insulin secretion— Acyl-ghrelin acutely suppresses insulin.

Do not use if

  • Active malignancy.
  • Uncontrolled diabetes - acyl-ghrelin acutely suppresses insulin secretion.
  • Significant hypotension, given the vasodilatory effect.
  • Pregnancy and breastfeeding.

Combining it

  • redundantghrp-6 — GHRP-6 is a synthetic mimic of exactly this molecule, with a far more practical half-life.
  • redundantmk-677 — Same receptor; MK-677 is orally active and lasts all day.
  • conflictsemaglutide — Directly opposing appetite signals.
  • cautioninsulin — Acyl-ghrelin acutely suppresses insulin secretion and raises glucose.

What to monitor

  • · In research settings, serial GH, glucose, insulin and blood pressure.
  • · There is no consumer use for which routine monitoring is defined, because there is no consumer use that makes pharmacological sense.

Legal status

Not an approved drug in any jurisdiction; supplied as a research reagent. Prohibited in sport under WADA S2.

References

  • Kojima et al. 1999 Nature, ghrelin is a growth-hormone-releasing acylated peptide from stomach (preclinical)
  • Human ghrelin infusion studies on appetite, GH release and energy intake (trial)
  • Reviews of ghrelin O-acyltransferase and the acyl versus des-acyl ghrelin distinction (review)

Mechanism in depth

The sequence above was retrieved directly from UniProt Q9UBU3: mature ghrelin-28 is GSSFLSPEHQRVQQRKESKKPPAKLQPR, with the third residue O-octanoylated. That single fatty acid is the whole story of why this molecule is a research reagent and not a drug. It is required for receptor activation, it is added post-translationally by ghrelin O-acyltransferase, and it is hydrolytically labile - so an acyl-ghrelin solution converts itself into an inactive peptide over time, and there is no shelf-stable formulation to be had. Every synthetic GHRP in this class exists to solve precisely that problem. Ghrelin is the only known peripherally produced orexigenic hormone, made mainly by X/A-like cells in the gastric fundus, rising before meals and falling after eating. Its actions divide into three streams. At the pituitary it releases GH by the standard GHS-R1a Gq/PLC/calcium route. In the arcuate nucleus it activates NPY/AgRP neurons and drives food intake, and it reaches those neurons partly through the median eminence, which sits outside the blood-brain barrier - which is why a peptide this size has central effects. Through vagal afferents and enteric signalling it accelerates gastric emptying. On top of that it has documented cardiovascular effects - improved cardiac output and reduced systemic vascular resistance - and anti-inflammatory effects on IL-6 and TNF-alpha. Circulating levels are chronically low in obesity and high in anorexia and cachexia, which is a genuinely counterintuitive pattern and one of the more interesting facts in metabolic endocrinology.

What usually goes wrong

The first problem is that what you buy is probably not active. The octanoyl ester at Ser3 hydrolyses, and grey-market 'ghrelin' is frequently des-acyl - the same 28 residues without the fatty acid, and completely inert at GHS-R1a. There is no way to tell by looking, and reconstituted acyl-ghrelin loses activity in days rather than weeks. The second problem is that even fully active product has a half-life measured in minutes, so any subcutaneous protocol delivers a brief pulse and nothing else, at a cost per milligram far above every synthetic alternative. The third is the acute haemodynamic effect: ghrelin reduces systemic vascular resistance, and an intravenous bolus can produce a meaningful transient blood pressure drop, which is a supervised-setting consideration rather than a bedroom one. The honest summary is that the entire GHRP class exists because ghrelin itself cannot be dosed usefully, and buying it is buying the problem that everything else in this class was invented to solve.

Bloodwork worth running

MarkerWhenWhy it matters
Serum growth hormone, glucose, insulin and blood pressureSerially through an infusion or after a bolus, in a supervised setting.In the research settings where ghrelin is actually administered, these are the measured outcomes rather than safety monitoring. The insulin suppression and the vasodilatory blood pressure drop are both real acute effects of an intravenous bolus.Act if: There is no consumer protocol for which a monitoring threshold makes sense, because there is no consumer use that makes pharmacological sense.

Pharmacokinetics

Crosses blood-brain barrier
partial
Metabolism
Two parallel routes, which is unusual. Esterase-mediated deacylation at Ser3 converts acyl-ghrelin to des-acyl ghrelin, which is inactive at GHS-R1a but circulates at higher concentrations and appears to have separate, partly opposing metabolic actions. Conventional proteolysis handles the peptide backbone.
Elimination
Renal handling of fragments. The kidney is also a significant site of ghrelin clearance.

Receptor targets

  • GHS-R1a (ghrelin receptor), pituitary somatotroph — The endogenous ligand - the reference by definition

    GH release. Rises within 15 to 30 minutes of intravenous administration.

  • GHS-R1a, arcuate NPY/AgRP neurons — Endogenous ligand

    The most consistent effect in human infusion studies: intense hunger and increased food intake.

  • GHS-R1a on vagal afferents and enteric neurons — Endogenous ligand

    Accelerated gastric emptying and increased gastrointestinal motility.

  • Cardiovascular system — Not fully characterised

    Improved cardiac output and reduced systemic vascular resistance in human studies. Clinically this presents as a transient blood pressure drop with intravenous bolus dosing.

  • Pancreatic beta cells — Not applicable

    Acyl-ghrelin acutely suppresses insulin secretion and raises glucose - which is the opposite of what most people assume a 'hunger hormone' does.

  • Ghrelin O-acyltransferase (GOAT) - the enzyme that makes it — Not applicable

    Not a target but the reason acyl-ghrelin exists. Without GOAT-mediated Ser3 octanoylation the peptide is inert at GHS-R1a.

What to expect, and when

GH and hunger both rise within 15 to 30 minutes of intravenous administration, and both are over within an hour or two. Flushing, warmth and a transient blood pressure drop are immediate with a bolus. There is no chronic timeline because there is no chronic use.

Stacking and comparisons

There is no sensible stack because there is no sensible use. Every synthetic GHRP in this class - GHRP-6, GHRP-2, hexarelin, ipamorelin, MK-677, anamorelin - is a stable mimic of this molecule with a practical half-life, and any of them is a better version of what ghrelin does. GLP-1 agonists oppose it directly. Insulin interactions are worth noting because acyl-ghrelin acutely suppresses insulin secretion and raises glucose, which is the opposite of the intuition most people have about a hunger hormone.

Against GHRP-6: GHRP-6 is a stable synthetic mimic of this exact molecule, with a longer half-life, no labile acyl group and a fraction of the cost. Against MK-677: orally active, lasts all day, and raises IGF-1 far more effectively. Against anamorelin: the same pharmacology in a form that made it through a phase 3 programme. There is no comparison in which ghrelin itself is the practical choice - it is the reference molecule, not a product. Its value is entirely in understanding what the rest of the class is imitating, and specifically in the observation that circulating ghrelin is low in obesity and high in anorexia and cachexia, which is the opposite of what a naive model would predict.

Rough cost

Sold as a research reagent by the milligram rather than as a therapeutic. Prices for research-grade acyl-ghrelin are far higher per milligram than any synthetic GHRP, and a monthly cost figure would be misleading because there is no monthly protocol. Des-acyl material is cheaper and inert.

Genuinely uncertain

  • No formal human pharmacokinetic parameters were resolved: no clearance, volume of distribution or bioavailability, and the 10 to 30 minute half-life figure has no primary source verified here.
  • The relative contribution of deacylation versus proteolysis to clearance is not established in the sources reached.
  • Des-acyl ghrelin's biology is genuinely unresolved. It circulates at higher concentrations than the acylated form, does not activate GHS-R1a, and appears to have separate and partly opposing metabolic actions through an unidentified receptor.
  • The Core record's molecular weight of 3370.9 was not independently confirmed and depends on whether the octanoyl group is counted.
  • Human infusion dose ranges of roughly 1 mcg/kg bolus or 5 pmol/kg/min are widely used in research but the specific figures were not verified against a primary publication in this session.
  • The cardiovascular effects are documented acutely but no chronic administration data exists in humans, and no therapeutic protocol has ever been established.
  • Whether commercially available 'ghrelin' is acylated is unverifiable without independent analysis and is the single largest practical uncertainty.

Papers