GHRP-6
Also known as Growth Hormone Releasing Peptide-6, SKF-110679, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
The first GHRP: ghrelin receptor agonist with marked hunger and a rise in cortisol and prolactin.
At a glance
- Category
- Growth hormone
- Status
- research chemical
- Route
- subcutaneous; intravenous and oral in study settings (oral bioavailability is low)
- Half-life
- approximately 15-20 minutes (human, subcutaneous)
- Onset
- GH peak within 15-30 minutes; hunger often within 20-40 minutes
- Molecular weight
- 873.0 g/mol
- Sequence
- His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (hexapeptide with two D-amino acids)
Historically important as the first synthetic GH-releasing peptide, through which the ghrelin receptor was discovered. There is no approved GHRP-6 medicine in the US or the EU. In the US its regulatory status is that of a compounding bulk substance placed by the FDA in category 2 — substances that may present significant safety risks — under the 503B interim policy on 29 September 2023. The FDA's stated grounds are a risk of immunogenicity for certain routes from aggregation and peptide-related impurities, and limited safety information that nonetheless reveals concerns including a potential effect on cortisol and an increase in blood glucose from decreased insulin sensitivity 4. It is otherwise sold as a 'research chemical'.
Doping status: Prohibited at all times (WADA S2, growth hormone secretagogues)
Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.
Mechanism of action
GHRP-6 is the original synthetic growth hormone-releasing peptide, derived from the enkephalin structure. It activates the growth hormone secretagogue receptor type 1a (GHS-R1a) on the anterior pituitary and in the hypothalamus. The discovery that GHRP-6 bound to a then-unknown receptor eventually led to the identification of ghrelin as the natural ligand of that receptor. All later GHRPs — GHRP-2, hexarelin, ipamorelin — and the non-peptide MK-677 were built on this.
Via the GHS-R1a receptor, GHRP-6 triggers a GH pulse through calcium signalling in the somatotroph cells, while simultaneously suppressing somatostatin tone in the hypothalamus. This pathway is separate from that of the GHRH analogues (sermorelin, tesamorelin, CJC-1295, mod GRF 1-29), which act on the GHRH receptor. Because the two pathways reinforce each other and cancel each other's inhibitory influence, combined administration of a GHRP and a GHRH analogue produces a GH response larger than the sum of the two individually — documented in humans as early as 1994 1.
GHRP-6 is the least selective of the class where appetite is concerned. As a full ghrelin mimetic it activates the NPY/AgRP neurons in the arcuate nucleus, producing a marked and sometimes hard-to-ignore sensation of hunger. This is considerably stronger than with GHRP-2 and virtually absent with ipamorelin. For anyone aiming at weight loss that is an important practical drawback; for people with reduced appetite it is precisely the intended effect.
Like GHRP-2 and hexarelin, GHRP-6 raises prolactin, ACTH and cortisol in addition to GH. The rise is generally milder than with hexarelin, but it is dose-dependent and real. Ipamorelin is the exception within this class in not showing these effects.
The GH potency of GHRP-6 is lower than that of GHRP-2 and hexarelin: a higher dose is needed for a comparable GH peak. In addition, preclinical research has described a GH-independent, cytoprotective action, among others on cardiac tissue and the intestinal wall, said to operate via GHS-R1a and CD36.
What the research shows
The acute GH, cortisol, prolactin and appetite effects in humans are well documented in small studies from the 1980s and 1990s. The historical importance of GHRP-6 is considerable, but there is no controlled evidence that prolonged use in healthy adults leads to more muscle mass, less fat mass or better recovery.
Research in humans
Several small studies in healthy volunteers, in children with growth retardation and in older adults characterised the dose-dependent GH response and the synergy with GHRH. The study by Popovic et al. (JCEM 1994) documented the synergistic action of GHRH plus GHRP-6 in healthy subjects 1. The appetite effect has been described in humans, but quantified less rigorously than with GHRP-2. There are no randomised long-term studies with functional endpoints.
Animal and lab research
Extensively studied: robust dose-dependent GH release in rats, pigs and dogs, plus increased food intake. Preclinical research additionally describes cytoprotective effects on cardiomyocytes and intestinal tissue that are partly independent of growth hormone.
Caveats. The human studies are small, mostly single-dose studies from the period 1984-2000, with hormone levels as the endpoint. GHRP-6 has largely been superseded pharmacologically by more potent (GHRP-2, hexarelin) or more selective (ipamorelin) successors, so research has stalled. There is no long-term safety data. Material sold as GHRP-6 falls outside any regulatory control of identity and purity.
What it is used for
- Historical: research tool through which the ghrelin receptor was discovered
- Studied as a GH secretagogue in growth hormone deficiency and as a pituitary stimulation test
- Outside research: raising one's own GH release, usually combined with a GHRH analogue
- Sometimes used for its marked appetite-stimulating effect, for instance in a bulking phase — an application without controlled evidence
Dosing
- There is no approved dosage. The ranges mentioned come from small clinical research and from user protocols.
- GHRP-6 is less potent than GHRP-2: a higher dose is needed for the same GH peak, and cortisol and prolactin therefore rise further along with it.
- The hunger effect is marked and often sets in within half an hour. For use aimed at fat loss this works against the goal; ipamorelin is then the more logical choice within the same class.
- Administration on an empty stomach: raised insulin and free fatty acids blunt the GH response. The sensation of hunger makes this hard to sustain in practice.
- In protocols it is almost always combined with a GHRH analogue because of the synergy between the two receptor pathways.
These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.
Protocols
GHRP-6, common user schedule
user protocol — not validatedSource: Pattern reported on forums and by vendors
This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.
| Before bed, on an empty stomach | 100 mcg subcutaneously, usually combined with a GHRH analogue in the same syringe |
|---|---|
| Optional further doses | up to three times daily, at least 3 hours apart |
| Range cited | 100-300 mcg per administration, with about 100 mcg (1 mcg/kg) as the usual starting point |
| Run length | 8-12 weeks, then a break |
GHRP-6 is less potent than GHRP-2, so reaching the same GH peak takes a higher dose and drags a larger cortisol and prolactin rise along with it. The hunger is pronounced and often begins within half an hour, which makes the empty-stomach requirement hard to keep to in practice and works directly against fat loss.
Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.
Reconstitution
- Vial sizes
- 5 mg, 10 mg
- Solvent
- bacteriostatic water (0.9% benzyl alcohol)
- Storage
- Reconstituted 2-8 °C, keeps for approximately 3-4 weeks. Powder in the freezer (-20 °C), protected from light.
Worked example
5 mg vial + 2.5 ml bacteriostatic water = 2 mg/ml. 100 mcg = 0.05 ml = 5 units on a U100 insulin syringe.
Let the water run down the wall of the vial; not directly onto the powder and do not shake.
Work it out for GHRP-6
Safety
Side effects
- Strong increase in appetite and hunger — the most characteristic effect and for many the reason to stop
- Rise in cortisol and ACTH, dose-dependent — the FDA names a potential effect on cortisol among the safety concerns it identified for GHRP-6 4
- Rise in prolactin; with continued use a theoretical risk of reduced libido, gynaecomastia or menstrual disturbance
- Fluid retention and oedema in hands and ankles
- Tingling and numbness in the hands; carpal tunnel syndrome is a class effect of GH elevation
- Joint and muscle pain
- Reduced insulin sensitivity and raised blood glucose — also named by the FDA among the safety concerns identified for GHRP-6 4
- Flushing, sensation of warmth, sweating and headache shortly after injection
- Drowsiness or fatigue
- Injection site reactions
- Partial decline of the GH response with continuous daily use
- Immunogenicity risk for certain routes of administration in compounded preparations, from the potential for aggregation and peptide-related impurities 4
Do not use if
- Active or previously treated malignancy — GH and IGF-1 are growth factors and the concern that they may stimulate existing malignant cells is theoretical but not refuted
- Hypercortisolism (Cushing's syndrome) or untreated adrenal disorder
- Hyperprolactinaemia or prolactinoma
- Diabetes mellitus or impaired glucose tolerance without medical supervision
- Active diabetic retinopathy
- Pregnancy and breastfeeding
- Children and adolescents with open growth plates, outside medical supervision
- Severe acute illness, after open heart surgery or in acute respiratory failure
- Eating disorders or situations in which an uncontrolled increase in appetite is harmful
Interactions
Glucocorticoids suppress the GH response; conversely, the cortisol rise caused by GHRP-6 may amplify the effect of glucocorticoid therapy. Somatostatin analogues block GH release. Raised GH and IGF-1 lower insulin sensitivity and may increase the need for antidiabetics. The prolactin rise may be amplified by concurrent use of dopamine antagonists (antipsychotics, metoclopramide). Concurrent use with a GHRH analogue produces a more than additive GH response. Other interactions have not been systematically studied.
Sources
- Growth hormone (GH) secretion in active acromegaly after the combined administration of GH-releasing hormone and GH-releasing peptide-6Journal of Clinical Endocrinology & Metabolism, 1994
- Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologiesMetabolism, 1996
- Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in manPeptides, 1997
- Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks — category 2 of the bulk substances nominated under sections 503A or 503B (growth hormone releasing peptide-6, 503B, added 29 September 2023)US Food and Drug Administration