GHRP-2

GHRP-2 (D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2), also called pralmorelin, is a synthetic "super-analogue" of GHRP-6 [1]. Like the rest of the family it acts at the ghrelin receptor, mostly at the hypothalamic level [3].

Acute potency. Compared head to head with hexarelin in six healthy young adults, 1 and 2 ug/kg intravenously produced near-identical growth hormone responses, both larger than the response to 1 ug/kg GHRH. In healthy people aged 66-73, both peptides again performed similarly [1]. In pigs, GHRP-2 was the most potent of the family tested, though with a lower maximum response than GHRP-6 or ipamorelin [4].

Synergy. GHRP-2 combines supra-additively with L-arginine in men and women, at rest and during exercise, with the rank order arginine+GHRP-2 > GHRP-2 > arginine > saline [5]. The same synergy holds with GHRH [2].

Repeated dosing. Bowers gave healthy younger and older adults GHRP-2, GHRH or both for 7-30 days. Chronic dosing with either changed the relationship between them, turning an additive combined response into a synergistic one, and whether the response desensitised depended on how much was given and how often [2].

In illness. A 21-hour infusion in patients with prolonged critical illness restored the normal temporal coupling between growth hormone, TSH and prolactin secretion, which infusions of GHRH or TRH did not [6].

What is missing is any trial of the thing people take it for. There is no controlled study of GHRP-2 on lean mass, fat mass, strength or sustained IGF-1 in healthy adults.

GHRP-2 is a GHS-R1a agonist. The receptor sits in both the pituitary and the hypothalamus, and the hypothalamic component dominates: in patients with a functional stalk disconnection, GH-releasing peptide produces essentially no growth hormone while GHRH still works normally, and the usual synergy between the two vanishes [3].

Selectivity is the weak point of this generation of peptides. Structure-activity work across the family shows growth hormone release and ACTH release can be separated by small changes in the peptide [7], but GHRP-2 itself has not been separated: its ACTH and cortisol response is about as large as CRH's [1]. In mice, GHRP-2 stimulates both secretion and synthesis of ACTH in the pituitary directly [8].

GHRP-2 is a hexapeptide, usually supplied as the acetate. The published human route is intravenous, by bolus or infusion [1][6]; in Japan it has been used as a single-dose diagnostic injection. Peptides in this family are routinely found in grey-market "growth" products, and an analysis of such products found contents that did not match their labels [9]. Urinary tests for GHRP-2 and GHRP-6 exist and are used in sport [10].

Human exposure in the published literature is almost entirely single intravenous doses in small volunteer groups, plus infusions in intensive care and up to 30 days of dosing in Bowers's studies [1][2][6]. No serious adverse effects are reported in those settings, but they are far too small and short to establish safety for ongoing use.

The predictable pharmacological problems are the cortisol and prolactin rises that come with every dose [1], and desensitisation of the growth hormone response with frequent dosing [2] — the same pattern hexarelin shows clearly over 16 weeks [11]. There are no published data on glucose, on IGF-1 over months, or on any long-term outcome.

GHRP-2 synergises with GHRH and with L-arginine on growth hormone release [2][5], and exercise potentiates its effect while shrinking the relative size of the synergy [5]. Its action requires an intact hypothalamus [3]. No interactions with other compounds on this site have been documented.