Ghrelin
Also known as: growth hormone-releasing peptide (endogenous), GHS-R ligand, acyl ghrelin, des-acyl ghrelin (inactive form), motilin-related peptide, GHRL (gene name), stomach-derived appetite peptide
Endogenous gastrointestinal peptide hormone — 28-amino-acid acylated peptide; growth hormone secretagogue (GHS); orexigenic agent; gastrointestinal prokinetic
What it is
Ghrelin is the body's primary hunger hormone, used in clinical research to treat severe appetite loss and muscle wasting in cancer, heart failure, and respiratory disease. It also stimulates growth hormone release and improves gut motility. Researchers and clinicians study it as a potential therapy where standard appetite treatments have failed.
The scientific side
ghrelin is a 28-amino-acid peptide hormone produced primarily by enteroendocrine X/A-like cells in the oxyntic glands of the gastric fundus, with secondary production in the hypothalamus, pituitary, intestine, pancreas, and other tissues. Its biological activity depends on n-octanoylation of serine-3, a post-translational acylation catalyzed by ghrelin O-acyltransferase (GOAT); the des-acyl (unacylated) form is the predominant circulating species but lacks activity at the canonical receptor. Ghrelin acts as the endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a), a Gq-protein-coupled receptor highly expressed in the anterior pituitary, hypothalamus, and numerous peripheral tissues. At the pituitary, GHS-R1a activation triggers phospholipase C signaling, intracellular calcium mobilization, and pulsatile release of growth hormone in a manner that is partially dependent on endogenous GHRH. In the hypothalamus, ghrelin stimulates orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons in the arcuate nucleus, potently increasing food intake and promoting a positive energy balance. This orexigenic signal is counterbalanced at baseline by leptin, insulin, and peptide YY acting on overlapping hypothalamic circuits. Peripherally, ghrelin accelerates gastric emptying and gastrointestinal motility via the enteric nervous system and vagal afferents, explaining its prokinetic utility in gastroparesis and functional dyspepsia. Plasma ghrelin levels rise sharply before meals and fall after feeding, making it the primary preprandial hunger signal; levels are chronically elevated in states of negative energy balance such as fasting, anorexia nervosa, and cancer cachexia, but paradoxically reduced in obesity. In the cardiovascular system, ghrelin improves cardiac output in heart failure through a GHS-R1a-dependent mechanism that increases cardiomyocyte contractility independently of calcium mobilization and reduces troponin I phosphorylation, without causing hypotension or arrhythmia. Additional mechanisms include anti-inflammatory actions via suppression of pro-inflammatory cytokines, attenuation of sympathetic nerve activity, and promotion of skeletal muscle anabolism through GH-dependent and GH-independent pathways. Following total gastrectomy, plasma ghrelin declines by 65–80%, explaining post-gastrectomy weight loss and appetite suppression.
Class: Endogenous gastrointestinal peptide hormone — 28-amino-acid acylated peptide; growth hormone secretagogue (GHS); orexigenic agent; gastrointestinal prokinetic
Legal & regulatory status
Not FDA-approved as a drug for human use. Ghrelin itself has no approved NDA or BLA. The ghrelin receptor agonist capromorelin (Entyce) was FDA-approved in 2016 for appetite stimulation in dogs and in 2020 (Elura) for…
Ghrelin and ghrelin mimetics (growth hormone secretagogues, GHS) are prohibited under the WADA Prohibited List. GHS fall under Section S2 — Peptide Hormones, Growth Factors, Related Substances and Mimetics — and are…
Ghrelin is not approved as a therapeutic drug by Health Canada. No Notice of Compliance (NOC) has been issued for any ghrelin-based human pharmaceutical in Canada. As an endogenous human peptide, it is not scheduled as…
What it's studied for
- Cancer cachexia — appetite stimulation and weight stabilization Human RCT
- Gastroparesis — accelerating gastric emptying and reducing symptoms Human RCT
- Chronic respiratory failure with cachexia — improved exercise tolerance, muscle mass, and appetite Human RCT
- Post-gastrectomy nutritional rehabilitation — weight recovery after stomach surgery Human RCT
- Heart failure with reduced ejection fraction (HFrEF) — improved cardiac output Human RCT
- Growth hormone stimulation testing and GH deficiency evaluation Human observational
- Anorexia nervosa — potential therapeutic and diagnostic role Human observational
Safety signals
- Flushing and gastric rumbles — most common adverse effects with IV ghrelin
- Transient hyperglycemia — ghrelin increases plasma glucose acutely
- Elevated ACTH and cortisol — neuroendocrine stimulation beyond GH axis
- Abnormal ghrelin dynamics in diabetic gastroparesis — diagnostic and pathophysiological complexity
- Rapid plasma degradation — short half-life limits clinical utility and necessitates continuous infusion
- Potential interaction with alcohol craving and reward pathways — neuropsychiatric considerations
- Stimulation of growth hormone and IGF-1 — theoretical oncological and proliferative concerns with chronic use
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | 0.1 μg/kg/min synthetic acyl ghrelin IV | — | Chronic HFrEF patients — acute cardiac output study | Research |
| Unspecified | 20–600 μg/kg IV (range studied); 80 μg/kg identified as effective dose | — | Gastroparesis patients — ghrelin receptor agonist TZP-101 (ulimorelin) | Research |
| Unspecified | 5.0 μg/kg synthetic ghrelin IV | — | Systemic sclerosis patients with GI involvement — gastric emptying study | Research |
| Unspecified | Not specified in abstract; ghrelin was administered as IV infusion or bolus across varied doses in 121 published studies | — | Healthy volunteers and mixed clinical populations — broad review | Research |
| Unspecified | Not specified in abstract for the RCT; exogenous recombinant ghrelin was administered IV or SC | — | Post-gastrectomy patients — nutritional rehabilitation | Research |
| Intravenous infusion or bolus in all reviewed clinical trials; subcutaneous and intranasal routes under investigation | Not established for community use; clinical studies used 0.1 μg/kg/min IV infusion (cardiac) or 5.0 μg/kg IV bolus (gastroparesis) | Varies by indication — acute single infusions to daily dosing studied | Research subjects; clinical study participants with cachexia, gastroparesis, or heart failure |
No peer-reviewed studies indexed for this peptide yet.