A 6-amino-acid synthetic peptide that stimulates growth hormone release by activating the ghrelin receptor (GHS-R1a). One of the first GH secretagogues developed. Notable for its strong appetite-stimulating effects and robust GH release, but less selective than ipamorelin.
GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide and one of the earliest growth hormone releasing peptides developed. It acts as a potent agonist at the ghrelin receptor (GHS-R1a), triggering robust GH release from the anterior pituitary.
Unlike the more selective ipamorelin, GHRP-6 also significantly stimulates appetite (via ghrelin pathway activation), increases cortisol and prolactin levels, and can cause intense hunger within 20 minutes of injection. This makes it less 'clean' than ipamorelin but potentially more effective for individuals who need appetite stimulation (e.g., recovering from illness or wasting conditions).
GHRP-6 is a non-selective GHS-R1a agonist that activates multiple downstream pathways. In addition to GH release from somatotrophs, it activates hypothalamic appetite circuits (mimicking ghrelin's orexigenic effect) and stimulates the HPA axis, increasing both cortisol and prolactin. This broad activation profile is why it has been largely replaced by ipamorelin for clinical use.
| Pathway | Effect | Significance |
|---|---|---|
| GH release | GHS-R1a activation on pituitary somatotrophs | Robust GH increase (greater magnitude than ipamorelin) |
| Appetite stimulation | Ghrelin-like activation of NPY/AgRP neurons in arcuate nucleus | Intense hunger within 20 min — useful for wasting, problematic for weight management |
| Cortisol increase | HPA axis stimulation via hypothalamic CRH release | Undesirable side effect not seen with ipamorelin |
| Prolactin increase | Pituitary lactotroph stimulation | Undesirable; can cause gynecomastia with chronic use |
| Gastric motility | Increases gastric emptying and GI motility | May benefit gastroparesis but can cause GI discomfort |
| Study | Design | Findings | Level |
|---|---|---|---|
| GH release | Phase I/II human studies | Dose-dependent GH increase peaking at 15-30 min post-injection. Greater magnitude than GHRP-2 or ipamorelin. | Level II |
| Appetite stimulation | Clinical observation | Significant hunger increase reported by virtually all subjects. Onset ~20 min, duration 1-2 hours. | Level II-III |
| Cardiac protection | Preclinical | GHRP-6 showed cardioprotective effects in ischemia-reperfusion models independent of GH release | Preclinical |
| Comparison to ipamorelin | Clinical studies | GHRP-6 produces greater GH release but with cortisol, prolactin, and appetite side effects that ipamorelin avoids | Level II |
Intense hunger: The most notable side effect. Can cause ravenous appetite within 20 minutes of injection.
Cortisol elevation: Chronic GHRP-6 use can elevate basal cortisol, potentially contributing to insulin resistance and fat accumulation.
Prolactin increase: May cause gynecomastia, galactorrhea, or menstrual irregularities with chronic use.
Water retention: GH-mediated fluid retention. Joint stiffness and carpal tunnel-like symptoms possible.
| Jurisdiction | Status |
|---|---|
| FDA | Not approved. |
| WADA | Banned under S2 (peptide hormones and growth factors) |
| Status | Largely superseded by ipamorelin in clinical use due to selectivity issues |
| Feature | GHRP-6 | Ipamorelin |
|---|---|---|
| GH release | Strong (higher peak) | Moderate (lower peak but cleaner) |
| Appetite effect | Intense hunger | Minimal |
| Cortisol | Increases significantly | No significant change |
| Prolactin | Increases | No significant change |
| Selectivity | Low (multiple off-target effects) | High (GH-selective) |
| Clinical preference | Wasting conditions, appetite loss | Anti-aging, body composition, general GH optimization |