GHRP-6
GHRP-6 — evidence, the ghrelin-discovery story & status

Class: peptide
Synonyms: GHRP-6
Growth Hormone Releasing Peptide-6
sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂. INCI: none
Function tags: GH secretagogue / ghrelin agonist
appetite stimulation
(research context)
Overall evidence grade: B
WADA prohibited: yes
WADA note: Sport: WADA-prohibited at all times — Section S2.2 (GH secretagogues).
Last updated: 2026-07-13

In brief: GHRP-6 is the original growth-hormone-releasing peptide (Bowers, 1984) — the compound from which the entire GH-secretagogue class descends, and whose study led to the discovery of the ghrelin receptor (1996) and ghrelin itself (1999). It reliably raises GH but is non-selective, producing the strongest appetite stimulation of any GHRP plus modest cortisol/prolactin. It is not approved anywhere, and the popular anti-aging / muscle use is untested in humans. Banned in sport.

## Identity a synthetic **hexapeptide** (6 amino acids, with two D-residues for protease resistance; < 40 aa → peptide), a **ghrelin-receptor (GHS-R1a) agonist**. Half-life ~2.5 h. ## Development & history - GHRP-6 was **the first growth-hormone-releasing peptide**, synthesised and characterised by **Cyril Y. Bowers at Tulane University in 1984** (Bowers, Momany, Reynolds, Hong). It emerged from systematic modification of **met-enkephalin analogs** — Bowers noticed some enkephalin derivatives had **unexpected GH-releasing activity unrelated to opioid receptors.** Every later GH secretagogue (GHRP-2, hexarelin, ipamorelin, the oral MK-677) descends from it.
- **The "fake key":** GHRP-6 activated a receptor no one had identified. Characterising it led first to the **cloning of the GH-secretagogue receptor (GHS-R1a) in 1996** (Howard et al.), and then — hunting for that receptor's *natural* ligand — to the **discovery of ghrelin in 1999** (Kojima & Kangawa, Osaka), found surprisingly in the **stomach**. GHRP-6 thus opened up the entire **ghrelin / gut-brain hunger-and-GH axis.** Its strong appetite effect, first dismissed as a side effect, turned out to be the crucial clue (ghrelin signals *both* hunger and GH). ## Mechanism (as proposed) GHRP-6 binds **GHS-R1a** on two populations — pituitary **somatotrophs** (driving GH release via the Gq-PLC-calcium pathway) and hypothalamic **arcuate-nucleus orexigenic neurons** (driving hunger). The *same* receptor drives both GH and appetite, exactly as endogenous **ghrelin** does physiologically. Its non-selectivity comes from additional HPA-axis (cortisol) and prolactin activation, plus gastric-motility effects.

Evidence grades by outcome:
outcome: GH release
grade: B
base: Extensive characterisation (Bowers 1984 onward) + human PK
effect: Strong, dose-dependent GH pulse
caveat: Real, foundational pharmacology
outcome: Appetite stimulation (cachexia / wasting research)
grade: C
base: Preclinical + Phase 1 observations
effect: Strongest of any GHRP
caveat: A feature for cachexia, a drawback for GH/fat-loss goals; preclinical as a therapy
outcome: Anti-aging / body composition / muscle (the popular use)
grade: F
base: None in humans
effect: Not demonstrated
caveat: Untested for these goals
outcome: Safety
base: Research + PK data
effect: Characterised (short-term)
caveat: Strong hunger; raises cortisol (~15–20% transient) and prolactin; long-term unknown; WADA-banned

Legal status:
region: INT
status: See note
note: - Everywhere — not approved for human therapeutic use; a research compound (503A Category-2 / gray-market). (Unlike GHRP-2, GHRP-6 has no approval anywhere.)
- ⚠ Sport: WADA-prohibited at all times — Section S2.2 (GH secretagogues).

Cosmetic claims:

Note: Reference entry — not sold here. Historically the most important peptide in this class: the first GHRP, and the compound whose study led to the discovery of ghrelin. Not approved anywhere; the marketed anti-aging use is untested in humans. No dosing published here.

Sources:
Bowers CY, Momany FA, Reynolds GA, Hong A. (Characterisation of GHRP-6 — the first GHRP.) 1984.
Howard AD, et al. (Cloning of the GH-secretagogue receptor, GHS-R.) Science, 1996.
Kojima M, Kangawa K, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999. (the endogenous ligand GHRP-6 pointed to)