Also known as: Growth Hormone Releasing Peptide-6 · His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂
| Parameter | Value | Data Source |
|---|---|---|
| Plasma t½ | ~15–20 min | Animal (rat) PK studies |
| Near-complete clearance | ~75–100 min (5× t½) | Extrapolated from animal data |
| GH pulse peak | ~15–30 min post-dose | Human + animal endocrine data |
| GH pulse duration | ~2–3 hours | Human + animal studies |
| Cortisol elevation | Yes — dose-dependent | Ghigo et al. 1993 (PMID 8350048) |
| Prolactin elevation | Yes — dose-dependent | Human endocrine data |
| ACTH elevation | Yes | Human endocrine data |
| Appetite stimulation | Strong — strongest among GHRPs | Pharmacological mechanism |
| IGF-1 buildup | Over 6–24 hours | GH downstream effect |
| Oral bioavailability | Not bioavailable | Peptide degradation |
| Data Quality | Animal Study + Limited Human Endocrine Data — human plasma PK not published | |
GHRP-6 (Growth Hormone Releasing Peptide-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂) is a synthetic hexapeptide that acts as a selective ghrelin receptor (GHSR-1a) agonist. It was the first GHRP discovered to have clinical potential, identified by Bowers et al. in 1984 — fifteen years before ghrelin itself was discovered.[1] The compound was initially identified through systematic modification of enkephalin analogues; its GH-releasing activity via the pituitary was characterised in that landmark 1984 Endocrinology paper.
Structurally, GHRP-6 is a six-amino-acid peptide (hexapeptide) with D-tryptophan at position 2 and D-phenylalanine at position 5, conferring metabolic stability over natural L-amino acid sequences. Its molecular weight is 873.0 Da. It is not orally bioavailable due to peptide hydrolysis in the GI tract and must be administered by injection for any research application.
GHRP-6 is a ghrelin receptor (GHSR-1a) agonist, discovered before ghrelin itself. When GHRP-6 was identified in 1984, its pituitary receptor was initially an orphan receptor. The discovery that this receptor was the endogenous ghrelin receptor — with ghrelin identified in 1999 by Kojima et al.[4] — retroactively established GHRP-6 as the first pharmacological probe of what became the ghrelin signalling axis. GHSR-1a activation proceeds via Gq/11 coupling, triggering IP3/DAG/calcium signalling in anterior pituitary somatotrophs and causing exocytosis of stored growth hormone granules. The resulting GH pulse peaks at approximately 15–30 minutes post-injection and sustains for approximately 2–3 hours.
Unlike the more selective ipamorelin, GHRP-6 co-stimulates cortisol, ACTH, and prolactin in a dose-dependent manner at GH-stimulating doses.[2] This is the principal pharmacological distinction from ipamorelin and is attributed to GHRP-6's less selective GHSR-1a interaction profile, with possible engagement of hypothalamic and extra-pituitary receptor populations and off-target receptor interactions. Published human data confirms cortisol elevation (Ghigo et al. 1993[2]; Arvat et al. 2001[2b]). This means GHRP-6 produces a broader endocrine response than ipamorelin, including HPA axis activation at standard research doses.
GHRP-6 produces pronounced hunger via ghrelin receptor activation in the arcuate nucleus of the hypothalamus and vagal afferents — the same pathway through which endogenous ghrelin increases appetite before meals. This orexigenic effect is the most clinically significant non-GH consequence of GHRP-6 administration and a primary reason researchers prefer ipamorelin or GHRP-2 for body composition protocols where appetite stimulation is not desired. The appetite stimulus typically lasts 1–3 hours post-injection and is consistently reported as the strongest appetite effect among the GHRP class.
Because GHRP-6's biological effects span multiple time scales — from peptide clearance to GH pulse to downstream IGF-1 accumulation — a three-layer model is the most accurate framework for understanding its duration of action.
Plasma t½ ~15–20 minutes (animal data — no peer-reviewed human PK study). Near-complete clearance at approximately 75–100 minutes (5 × 15 min).
Even as the peptide clears rapidly, the triggered GH pulse peaks at ~15–30 min and persists for approximately 2–3 hours. Cortisol elevation lasts approximately 2–4 hours. Hunger stimulus begins within minutes of injection and lasts approximately 1–3 hours. These downstream effects substantially outlast the peptide itself.
GH pulses drive hepatic IGF-1 secretion over 6–24 hours. With chronic multi-dose protocols (2–3×/day), IGF-1 levels build cumulatively over days. HPA axis co-stimulation with repeated GHRP-6 dosing may have cumulative consequences; long-term human safety data does not exist.
| Route | Status | Notes |
|---|---|---|
| SC injection | Research route | No formal human PK study; human GH + endocrine response data exists |
| IV | Used in original research | Used in Bowers et al. animal studies and subsequent human endocrine studies |
| IM | No published data | Not characterised |
| Oral | Not bioavailable | Peptide hydrolysis in GI tract; no oral formulation exists |
GHRP-6 is the least selective GHRP. Ipamorelin was specifically developed to provide equivalent GH stimulus without the cortisol, prolactin, and appetite effects.[3]
| Compound | GH Stimulus | Cortisol | Prolactin | Appetite | Key Reference |
|---|---|---|---|---|---|
| GHRP-6 | +++ GH | Yes — significant | Yes — significant | Strong | Bowers 1984 [1] |
| Ipamorelin | +++ GH | No | No | Mild | Raun 1998 [3] |
| GHRP-2 | +++ GH | Yes | Yes | Moderate | Animal + human data |
| Hexarelin | ++++ GH | Strong | Strong | Moderate | Human data |
| MK-677 | +++ GH | Mild/variable | Variable | Strong | Human RCT data |
The Halflife app models your GHRP-6 concentration curve alongside the GH pulse window — see exactly when each dose peaks and how stacking with CJC-1295 changes the curve. On-device, no account required.
Download on App StoreGHRP-6 holds a unique place in endocrinology history. Bowers et al. (1984)[1] identified it as a potent synthetic GH secretagogue acting on pituitary cells through a receptor distinct from the GHRH receptor. For 15 years this receptor remained orphan — its endogenous ligand unknown. In 1999, Kojima et al.[4] identified ghrelin as the endogenous ligand for this receptor (thereafter named GHSR-1a), completing the pharmacological loop. GHRP-6 was thus the synthetic ligand that guided the search for ghrelin — one of the few cases in pharmacology where the synthetic agonist preceded the discovery of the natural ligand by over a decade.
Stack GHRP-6 with CJC-1295, ipamorelin, or MK-677 and see the combined PK curves update in real time. Free iOS app — all calculations on device, no account needed.
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