GHRP-6

GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is the compound that started this field. It was built from opioid peptide fragments in the search for a growth hormone releaser that did not work through GHRH, and the receptor it acts on — the growth hormone secretagogue receptor — was later shown to be the receptor for ghrelin.

How strong it is. In 11 healthy adults, 90 ug intravenously produced a growth hormone area under the curve of 1,435 against 484 for 100 ug of GHRH. Given together, the response was 3,772, significantly more than the sum of the two given separately [1].

Where it acts. The same study gave the answer. In 12 patients whose pituitary was functionally disconnected from the hypothalamus, the GHRH response was normal but the GHRP-6 response was completely blocked, and the synergy disappeared. The main site of action is therefore the hypothalamus [1].

Age. Growth hormone secretion declines with age, and so does the response to GHRH. The response to GHRP-6 does not: in young and late-adulthood groups, GHRP-6 alone and GHRP-6 plus GHRH produced statistically indistinguishable responses, while GHRH alone was weaker in the older group. The authors read this as evidence that the age-related decline is functional and reversible [2].

Pharmacokinetics. Nine healthy men received 100, 200 or 400 ug/kg intravenously. Disposition was biexponential with a distribution half-life of 7.6 minutes and an elimination half-life of 2.5 hours, and area under the curve rose in proportion to dose [3].

Other settings. GHRP-6 has been used with GHRH to probe pituitary reserve in polycystic ovary syndrome [5] and in type 2 diabetes, where hyperglycaemia blunted the response [6]. A Cuban group has pursued it as a tissue-protective agent, reporting benefit in animal models of acute lung injury [7]; none of that work has reached controlled human trials.

GHRP-6 activates GHS-R1a. Because most of its effect is hypothalamic [1], it works partly by opposing somatostatin and partly by releasing endogenous GHRH, which is why the combination with GHRH is supra-additive rather than simply additive. The same logic explains why arginine, which suppresses somatostatin, potentiates peptides of this class in older people [8].

The receptor's other job is appetite: it is ghrelin's receptor, so appetite stimulation comes with the growth hormone release. Selectivity for growth hormone is poor — ACTH and cortisol rise too [4] — and it was precisely this that later peptides were designed to avoid [9]. The pharmacology of the whole GH-releasing peptide family was reviewed in detail as it emerged [10]. Structure-activity studies across the family map which residues carry which effect [11].

GHRP-6 is a hexapeptide of molecular weight about 872 Da, supplied as an acetate salt; the published human route is intravenous [3]. Products sold on the grey market as growth peptides frequently do not contain what their labels claim [12]. GHRP-6 and GHRP-2 are both detectable in urine and are prohibited in sport [13].

The human record is single intravenous doses, up to 400 ug/kg, in small groups of healthy volunteers and patients, with no serious adverse effects reported [1][3]. That is not a safety dataset for repeated use.

The known pharmacological effects to expect are increased appetite, and a rise in ACTH and cortisol at growth hormone-releasing doses [4]. Hexarelin, a close analogue, loses about half its growth hormone effect over 16 weeks of twice-daily dosing [15], and the same is likely here, though it has not been measured. There is no data on glucose, IGF-1 over time, or long-term outcomes.

GHRP-6 and GHRH are strongly synergistic, and that synergy depends on an intact hypothalamus [1]. High blood glucose blunts the growth hormone response to the combination [6]. No interactions with other compounds on this site have been documented.