Class 09 · GH secretagogues · Ghrelin / GHSR-1a agonists · Hexapeptide

GHRP-2pralmorelin · diagnostic GH secretagogue

A synthetic six-amino-acid peptide that triggers a short, sharp burst of growth hormone by mimicking ghrelin — the body's "hunger hormone." It produces the highest peak GH release of any classic GHRP, but its only legitimate approved use is a diagnostic test for growth-hormone deficiency, not anti-aging or performance. Approved in Japan as a single-dose diagnostic agent (GHRP Kaken 100); not FDA-approved in the U.S. Prohibited at all times in sport under WADA category S2.

Synthetic hexapeptide growth-hormone secretagogue and ghrelin/GHSR-1a agonist. Stimulates pituitary somatotrophs to release GH, amplifies endogenous GHRH signaling, and suppresses somatostatin (the body's GH brake) — a three-pronged drive that yields the strongest peak GH of the traditional GHRPs. In a pediatric IV PK/PD study (1 µg/kg), GH rose to Cmax ≈ 50.7 ng/mL at Tmax ≈ 0.42 h; GHRP-2 terminal β-half-life ≈ 0.55 h. Not GH-selective: human studies show concurrent rises in prolactin, ACTH and cortisol. No long-term therapeutic outcome RCTs exist.

Pralmorelin — D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂ (C₄₅H₅₅N₉O₆, MW ≈ 817.97 Da, CAS 158861-67-7, PubChem CID 6918245) — a met-enkephalin–derived hexapeptide incorporating non-natural D-residues for protease resistance. Classified by IUPHAR as a pralmorelin ligand activating the ghrelin/GHS receptor (GHSR-1a), a Gq/11-coupled GPCR. Co-administration with a GHRH analog such as CJC-1295 produces a GH pulse markedly larger than either agent alone — the basis of "GHRH + GHRP" synergy. Former development codes KP-102, GPA-748, WAY-GPA-748 (Bowers / Kaken).

~50.7 GH Cmax (ng/mL) · 1 µg/kg IV · pediatric · Pihoker 1998

0.55 h GHRP-2 terminal β-half-life · IV

100 µg Japan diagnostic IV dose (adult, fasting)

S2 WADA class · prohibited at all times

Status

Japan diagnostic · US not approved · WADA-prohibited

Open dose calculator →

Frequency

Single IV (diagnostic) · SC research

Originator

Bowers / Kaken · KP-102 · 1980s–90s

Peak GH rank

Highest of classic GHRPs

Molecule identity

C₄₅H₅₅N₉O₆

Pralmorelin · met-enkephalin–derived synthetic hexapeptide · SPPS

ClassGH secretagogue · ghrelin mimetic

SequenceD-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂

Molecular weight817.97 Da free base · CID 6918245

Salt formdiHCl ≈ 890.9 Da CID 9940988

Receptor targetGHSR-1a · Gq/11–PLC–Ca²⁺

Primary effectPituitary GH pulse amplification

Half-life (IV)≈ 0.55 h (β) Pihoker 1998

RoutesIV (Dx) · SC (research) · intranasal · oral (historical)

ApprovalJapan diagnostic only · US: none

WADAS2 · prohibited at all times 2026 list

Former codesKP-102 · GPA-748 · WAY-GPA-748

01 · At a glance

What GHRP-2 is — and what it is not.

GHRP-2 is among the most potent classic growth-hormone–releasing peptides by peak GH output. It has a real, narrow legitimate role — diagnosing growth-hormone deficiency — and a much larger speculative use space (anti-aging, body composition, performance) that is unapproved and carries a non-selective endocrine risk profile.

🩺

Primary use case

Diagnostic

Best-supported human use is provocative diagnostic testing of GH secretion — approved in Japan as GHRP Kaken 100 — not chronic anti-aging or performance use. Grade B.

🔑

Mechanism headline

GHSR-1a

Activates GHSR-1a / ghrelin-receptor signaling to stimulate pituitary GH release, with hypothalamic GHRH interaction contributing, plus somatostatin suppression. Grade B/C.

📊

Strongest evidence tier

Human PD

Human PK/PD studies show robust GH release after IV or SC dosing; long-term clinical outcome evidence is limited. Grade B.

🏔️

Peak-GH ranking

Highest GHRP

Produces the highest peak GH of the traditional GHRPs — stronger than GHRP-6 or ipamorelin per unit dose, with a cleaner appetite profile than GHRP-6. Grade B.

💉

Typical research dose

100 µg

Human studies include 1 µg/kg IV (diagnostic) and 100 µg/day SC short-course; community SC ranges are unapproved (Grade D).

⚖️

Key risk · non-selectivity

PRL · ACTH

Raises GH but also prolactin, ACTH and cortisol; appetite stimulation; pregnancy contraindicated in the Japanese label. Grade B.

🍽️

Appetite signature

Moderate ↑

Ghrelin-like: acutely increases hunger and food intake in healthy men — present but weaker than GHRP-6's intense hunger. Grade B.

⚠️

Regulatory status

Rx (JP)

Not FDA-approved; FDA flags injectable/nasal GHRP-2 in compounding-risk context; WADA-prohibited at all times. Grade D.

02 · Mechanism of action

How GHRP-2 drives a growth-hormone pulse.

GHRP-2 copies part of the ghrelin signal and pushes the pituitary to release GH through three converging actions at once — GHSR-1a agonism, GHRH facilitation, and withdrawal of the somatostatin "brake." The receptor is not GH-exclusive, so prolactin, ACTH and cortisol can co-rise, and ghrelin-type appetite signaling is engaged in parallel.

Grade B/P

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1 · GHSR-1a / ghrelin receptor agonism

GHRP-2 binds and activates the growth-hormone secretagogue receptor (GHSR-1a) — the same receptor targeted by the gut hormone ghrelin — to initiate the GH-release cascade in pituitary somatotrophs.

Clinical significance: Because GHRP-2 works through the ghrelin receptor rather than the GHRH receptor, it raises GH even when GHRH signaling is blunted, and it engages ghrelin-type appetite circuitry as a side effect. This receptor independence is why GHRPs are useful provocative agents and why they synergize with GHRH analogs. GHSR is broadly expressed and mediates endocrine and metabolic actions.

Molecular detail: GHSR-1a is a class-A GPCR coupled predominantly to Gq/11 → phospholipase Cβ → IP₃/DAG → intracellular Ca²⁺ mobilization and PKC activation, with high constitutive activity. IUPHAR classifies pralmorelin as a ghrelin/GHS-receptor agonist (ligand 1092). The non-natural D-Ala¹ and D-2-naphthylalanine² residues confer protease resistance and high receptor affinity relative to earlier GHRP-series peptides.

Grade B

📈

2 · Pituitary GH pulse amplification

The principal measurable effect is a sharp, transient GH pulse beginning minutes after administration and peaking under an hour — among the largest peak GH responses of any classic GHRP.

Clinical significance: The pulse is brief and self-limiting, which is exactly what a provocative diagnostic test requires: a reproducible, time-locked GH surge to distinguish GH-deficient from GH-sufficient patients. In children given 1 µg/kg IV, GH Cmax ≈ 50.7 ± 17.2 ng/mL at Tmax ≈ 0.42 h, with GH elimination half-life ≈ 0.37 h. GHRP-2 yields higher peak GH than GHRP-6 or ipamorelin at matched doses.

Molecular detail: The response fits a PK/PD link model in which GHRP-2 plasma concentration drives GH secretion with an estimated EC₅₀ ≈ 1.09 ± 0.59 ng/mL in the pediatric IV study. GHRP-2 disposition was biexponential: terminal β-half-life 0.55 ± 0.14 h, clearance 0.66 L/h/kg, Vd 0.32 L/kg. Pulse magnitude is dose- and age-dependent and exhibits partial tachyphylaxis with repeated daily exposure.

Grade B/C

🔗

3 · Hypothalamic GHRH facilitation

GHRP-2 works best when the body's own growth-hormone-releasing hormone (GHRH) system is intact — the two signals reinforce each other at the pituitary.

Clinical significance: Subjects with GHRH-receptor mutations mount a different GHRP-2 GH response than controls, showing the effect is not pure direct somatotroph stimulation — hypothalamic/GHRH integrity matters. In GHRH-receptor–deficient subjects, GHRP-2's GH response pattern implicated a hypothalamic contribution. This is the mechanistic foundation for combining GHRP-2 with a GHRH analog.

Molecular detail: GHRP/GHSR signaling (Gq/11–PLC–Ca²⁺) converges with GHRH-receptor signaling (Gs–cAMP–PKA) at the somatotroph, producing more-than-additive GH release. Co-administration of GHRP-2 with a GHRH analog such as CJC-1295 produces a GH pulse substantially larger than either alone. GHRP-2 additionally withdraws somatostatin tone, removing inhibitory input onto the same cells.

Grade B

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4 · Somatostatin suppression (GH-brake withdrawal)

Beyond pushing the GH accelerator, GHRP-2 lifts the GH brake: it reduces the inhibitory tone of somatostatin (GHIH), the hormone that normally suppresses GH release.

Clinical significance: Suppressing somatostatin while simultaneously stimulating GHSR-1a and facilitating GHRH is why GHRP-2 generates the highest peak GH of the traditional GHRPs. GHRP-2 enhances GH release in part by restricting somatostatin (growth-hormone-inhibiting hormone) activity. It also explains why pre-existing high somatostatin tone (hyperglycemia, elevated free fatty acids) blunts the response.

Molecular detail: Functional antagonism of somatostatinergic input is thought to occur at both hypothalamic (arcuate/periventricular) and pituitary levels, disinhibiting cAMP/Ca²⁺-dependent GH exocytosis. General pharmacology of KP-102 (GHRP-2) characterized its potent, specific GH-releasing profile. The triple action — agonism + GHRH facilitation + somatostatin withdrawal — is the canonical GHRP mechanism model.

Grade B/P

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5 · Appetite / feeding-behavior signaling

Like ghrelin, GHRP-2 acutely increases hunger and food intake — a direct consequence of activating the same gut–brain ghrelin receptor.

Clinical significance: Appetite stimulation is a predictable, dose-related effect that can be a liability (weight gain, glycemic load) or, in wasting/cachexia contexts, a potential benefit. In healthy men, GHRP-2 acutely stimulated food intake, like ghrelin. GHRP-2's appetite effect is moderate — present but weaker than GHRP-6's intense hunger.

Molecular detail: Orexigenic signaling proceeds through GHSR-1a on hypothalamic arcuate-nucleus NPY/AgRP neurons, increasing orexigenic drive and meal initiation downstream of ghrelin-receptor activation. The effect is consistent with the central ghrelin appetite pathway. This central action is distinct from — and parallel to — the somatotroph GH effect.

Grade C/B

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6 · ACTH / cortisol / PRL co-activation & IGF-1 downstream

GHRP-2 is not perfectly GH-selective: it can also nudge stress hormones (ACTH, cortisol) and prolactin, and — only if GH pulses are sustained — may raise IGF-1.

Clinical significance: The non-selective endocrine envelope is the main mechanistic safety concern for repeated use. Human comparison of GHRP-2 and hexarelin showed GH release alongside increases in PRL, ACTH and cortisol. Five days of once-daily SC GHRP-2 in healthy young men did not clearly raise IGF-1, underscoring that frequency and exposure pattern govern any downstream effect.

Molecular detail: HPA-axis activation may involve hypothalamic CRH/AVP interactions or GHSR signaling on corticotrophs; the exact pathway is unresolved. Downstream, hepatic GH-receptor activation drives JAK2/STAT5-mediated IGF-1 transcription, which GHRP-2 engages only indirectly via GH pulsatility. Animal repeated-dosing data show frequency-dependent GH/IGF-1 dynamics.

L3 · Cascade

Signaling cascade — exposure to GH pulse

💉 GHRP-2

IV / SC

→

🔑 GHSR-1a

Gq/11 · PLC · Ca²⁺

→

⚙️ GHRH↑ · SST↓

convergent drive

→

📈 GH pulse

Tmax ≈ 0.4 h

→

🔄 IGF-1 · risk envelope

PRL · ACTH · appetite

L3 · Mechanism summary

The three converging drives — and the off-target envelope

Driver	Site / pathway	Net effect on GH	Evidence
GHSR-1a agonism	Somatotroph · Gq/11–PLC–Ca²⁺	Direct secretion ↑	Receptor pharmacology
GHRH facilitation	Hypothalamus/pituitary · Gs–cAMP	Amplifies pulse	GHRH-R-deficient study
Somatostatin withdrawal	Removes GH brake	Disinhibits pulse	Active even with somatostatin present
Off-target: PRL	Lactotroph	—	Human comparison
Off-target: ACTH/cortisol	HPA axis · CRF-mediated	—	CRF-mediated in rats
Off-target: appetite	Arcuate NPY/AgRP	—	Human appetite study

L3 · PK summary

Human pharmacokinetics (1 µg/kg IV, pediatric)

Parameter	Value	Note
GHRP-2 terminal β-half-life	0.55 ± 0.14 h	Pihoker 1998
GHRP-2 Cmax	7.4 ± 3.8 ng/mL	Biexponential disposition
Clearance	0.66 ± 0.32 L/h/kg	—
Volume of distribution	0.32 ± 0.14 L/kg	—
GH Cmax (response)	50.7 ± 17.2 ng/mL	Peak GH output
GH Tmax	0.42 ± 0.16 h	Fast, brief pulse
GH elimination half-life	0.37 ± 0.15 h	Self-limiting
PK/PD link EC₅₀	1.09 ± 0.59 ng/mL	Concentration drives GH

03 · Dosing protocols & models

Route-specific dosing models.

Only the Japanese intravenous diagnostic use has clear label-level support. Every other model below — subcutaneous research, intranasal, oral, and GHRH-combination — is a research-page hypothesis scaffold, not a recommendation. GHRP-2 is not FDA-approved; non-diagnostic protocols are speculative and carry a non-selective endocrine risk profile (PRL/ACTH/cortisol/appetite).

Important · regulatory status GHRP-2 / pralmorelin is approved in Japan as GHRP Kaken 100 for diagnostic evaluation of growth-hormone deficiency only — not as a chronic therapeutic, performance, anti-aging, body-composition, or wellness drug. The Japanese label describes a 100 µg vial: adults receive 100 µg fasting IV; ages 4–17 receive 2 µg/kg up to a 100 µg cap, reconstituted in 10 mL saline immediately before use. In the U.S. GHRP-2 is not FDA-approved, and FDA has identified injectable and nasal GHRP-2 among bulk drug substances that may present significant safety risks in compounding contexts. It is prohibited at all times in sport under WADA category S2. All non-diagnostic use is investigational and requires physician supervision.

PK / PD anchor The best-cited human study administered 1 µg/kg IV to ten prepubertal children: GHRP-2 disposition was biexponential with terminal β-half-life 0.55 ± 0.14 h, Cmax 7.4 ± 3.8 ng/mL, clearance 0.66 ± 0.32 L/h/kg, and Vd 0.32 ± 0.14 L/kg; the GH response had Cmax 50.7 ± 17.2 ng/mL, Tmax 0.42 ± 0.16 h, and GH elimination half-life 0.37 ± 0.15 h. This single IV diagnostic exposure is the firmest quantitative anchor; all multi-dose / SC models extrapolate beyond it.

Use case

GH-stimulation / severe GH-deficiency diagnostic testing — the only label-supported indication.

Starting dose

100 µg IV fasting (adults); 2 µg/kg IV capped at 100 µg (ages 4–17). Japanese GHRP Kaken 100 label

Escalation

None — a single provocative test dose. No ladder.

Maintenance

None. Not a treatment regimen.

Reconstitution

100 µg vial reconstituted with 10 mL saline immediately before use; administered as a slow IV push under supervision.

Monitoring

Serial GH sampling (0/15/30/45/60 min), fasting status, blood pressure, symptoms, glucose context, pregnancy exclusion.

Warnings

Pregnancy contraindicated in the Japanese label; diagnostic interpretation depends on local assay and cut-offs.

Diagnostic single dose only. Grade B for the diagnostic dose; D for any extrapolation outside provocative testing.

Dose bands · IV

Global dose-band reference (working unit µg)

Band	µg range	≈ µg/kg @ 70 kg	Basis	Grade
Diagnostic IV	100 µg once	~1.4 µg/kg once	Japanese label adult fixed dose; pediatric 2 µg/kg cap 100 µg	B
Low research SC	50–100 µg/day	0.7–1.4	Anchored to human SC 100 µg/day short course	B/D
Standard research SC	100–200 µg/day	1.4–2.9	Practice-pattern hypothesis; not approved	D
High research SC	200–300 µg/day	2.9–4.3	High-end hypothesis; higher endocrine side-effect concern	D/P
Multi-dose daily	Not validated	Not validated	Online/bodybuilding protocols — not evidence-based	D

Titration logic · diagnostic

Diagnostic test decision points

Trigger	Action	Rationale
Pregnancy or possible pregnancy	Do not administer	Contraindicated in Japanese label
Non-fasting / recent meal	Reschedule	Somatostatin tone and substrate confound GH response
Flat GH response	Interpret per local cut-off	Supports GH-deficiency diagnosis in clinical context
Competitive athlete	Document medical use	WADA-prohibited substance

Biomarker scaffold · diagnostic

What is measured during the test

Marker	Use	Validated for GHRP-2?
Serial GH (ng/mL)	Primary diagnostic endpoint	Yes — diagnostic context only
Blood pressure	Acute safety	Supervised-setting monitoring
Glucose	Context for GH interpretation	Context only
IGF-1 (baseline)	Background GH-axis status	Adjunct, not GHRP-2-specific

Interpretation reference · diagnostic

Reading the GH-stimulation result

Pattern	Interpretation	Caveat
Robust GH peak	GH-sufficient response	Assay- and cut-off-dependent
Blunted / flat peak	Supports GH-deficiency in context	Confirm with clinical picture / second test
Discordant result	Repeat or use alternative provocative test	No single test is definitive

Use case

Human GH-pulse research; the basis for most community SC dosing — none of which is approved treatment.

Study basis

100 µg SC once daily × 5 days in healthy young men. Nijland 1998: GH response persisted across 5 days; IGF-1 effect limited

Escalation

No validated escalation. Conservative research bands 50 → 100 → 150–200 µg per administration are hypothesis modeling only.

Cycle / washout

Human study ran 5 days; longer cycles are unvalidated (D/P).

Reconstitution

Common research default: 5 mg vial + 2 mL BAC = 2,500 µg/mL (see calculator).

Monitoring

IGF-1, fasting glucose/A1c, edema, BP, carpal-tunnel symptoms, headache, appetite, sleep, PRL/cortisol if symptomatic — all monitoring hypotheses, not validated algorithms.

Potential PRL/ACTH/cortisol co-release. Avoid in pregnancy, active malignancy, uncontrolled diabetes, or intracranial/pituitary mass without specialist evaluation. Grade B for acute GH release / short course; D for wellness protocols.

Dose ladder · SC

Conservative SC research ladder (hypothesis only)

Step	Dose	Hold for	Grade
Step 1 (screen)	50 µg SC	Tolerability: nausea, BP, flushing	D
Step 2	100 µg SC	Matches the human short-course study dose	B/D
Step 3 (cap)	150–200 µg SC	Higher endocrine side-effect concern; do not exceed without oversight	D/P

Weight-band scaffold · SC

Weight-band interpolation (calculator scaffold, not a recommendation)

Body weight	1.0 µg/kg	1.5 µg/kg	2.0 µg/kg
55 kg	55 µg	82.5 µg	110 µg
65 kg	65 µg	97.5 µg	130 µg
75 kg	75 µg	112.5 µg	150 µg
85 kg	85 µg	127.5 µg	170 µg
95 kg	95 µg	142.5 µg	190 µg
105 kg	105 µg	157.5 µg	210 µg

Titration logic · SC

Titration decision logic

Trigger	Action	Rationale
Fasting glucose worsens / A1c trends up	Hold or de-escalate	GH/IGF-1 axis can worsen insulin resistance
IGF-1 above age-adjusted range	Hold	Excessive downstream GH-axis stimulation
Edema, carpal-tunnel, paresthesias, headache	De-escalate or stop	GH-axis adverse-effect pattern
New/worse sleep-apnea symptoms	Hold	GH-axis fluid/tissue effects
Elevated PRL or symptoms	Hold and evaluate	GHRP-2 may increase PRL
Anxiety, insomnia, high-cortisol symptoms	De-escalate or stop	ACTH/cortisol may rise
Pregnancy or possible pregnancy	Hard stop	Contraindicated
Active malignancy / unexplained mass	Hard stop	Theoretical IGF-1 proliferative risk
WADA-tested athlete	Hard stop	Prohibited at all times

Biomarker scaffold · SC

Biomarker monitoring scaffold (none validated for non-approved GHRP-2 protocols)

Marker	Why monitor	Validated?
IGF-1	Downstream GH-axis exposure	No
Fasting glucose	GH-axis insulin-resistance signal	No
HbA1c	Longer-term glycemic trend	No
Fasting insulin / HOMA-IR	Insulin-resistance hypothesis	No
Prolactin	GHRP-2 may raise PRL	No — mechanistically relevant
Morning cortisol / ACTH	GHRP-2 may raise ACTH/cortisol	No — mechanistically relevant
Blood pressure	Fluid retention / metabolic risk	No
Weight / waist	Appetite / body-composition tracking	No
Sleep-apnea symptoms	GH-axis soft-tissue/fluid concern	No

Use case

Investigational delivery and anti-doping detection literature; not approved routine therapy.

Dose

No validated clinical dose for treatment; avoid page-level dosing claims except "investigational."

Reconstitution

Not suitable for a clinical calculator unless a validated formulation exists.

Monitoring

Same endocrine scaffold; plus nasal irritation and formulation-sterility concerns.

Warnings

FDA specifically names nasal GHRP-2 among routes of concern in the compounding context.

Detection-science and formulation interest only. No protocol-grade dosing. Grade D/P.

Detection context · intranasal

Why intranasal appears in the literature

Context	Note	Grade
Anti-doping detection	GHRPs including GHRP-2 are detectable by LC/MS urinary metabolite methods after administration	B/D
Bioavailability	Nasal exposure differs from SC/IV; do not convert doses across routes	P
Formulation	No validated sterile intranasal product	D

Historical formulation · KP-102LN

The nasal-spray development line

Item	Detail	Status
KP-102LN	Kaken nasal-spray formulation of pralmorelin for pediatric growth disorders	Investigational (historical)
Outcome	GH rose but growth outcomes were disappointing in trials	Development discontinued
Implication	GH elevation ≠ clinical growth benefit — a key honesty point for any route	Lesson

Use case

Historical development notes describe pralmorelin as orally active, but practical therapeutic oral dosing is not established.

Dose

Not established. Do not provide a calculator-enabled oral protocol without a validated PK source.

Reconstitution

Not applicable.

Warnings

Oral bioavailability and exposure-response are not sufficiently established for protocol modeling.

Of historical interest (KP-102 development). Macimorelin — a different, FDA-approved oral ghrelin-receptor agonist — is the legitimate oral diagnostic comparator. Grade D.

Historical note · oral

Oral GHRP context

Point	Detail	Grade
Oral activity	Pralmorelin development reviews note oral activity (KP-102 program)	D
Therapeutic oral dose	Not established for non-diagnostic use	D
Oral comparator	Macimorelin — FDA-approved oral ghrelin-receptor agonist for adult GHD diagnosis	A (for macimorelin)

Formulation history · oral

Why oral GHRP never became a therapeutic

Factor	Detail	Implication
Bioavailability	Oral peptide exposure is low and variable	Hard to dose reproducibly
Development path	The program settled on IV diagnostic use in Japan	Oral never reached approval
Modern oral option	Macimorelin is the approved oral ghrelin-receptor diagnostic	Use the approved agent for oral diagnosis

Use case

Mechanistic GH-secretagogue synergy research. Practice discussion pairs GHRP-2 with a GHRH analog such as sermorelin or CJC-1295 (no DAC) — not approved GHRP-2 dosing.

Rationale

GHRP and GHRH act through distinct receptors converging at the somatotroph; co-administration produces a GH pulse markedly larger than either alone.

Escalation

Avoid escalation if IGF-1 rises above age-adjusted range, or edema, BP/glucose worsening, or PRL/cortisol symptoms appear.

Reconstitution

Separate calculator blocks for each peptide; do not combine concentrations in one vial unless validated.

Monitoring

IGF-1, glucose, BP, edema, sleep-apnea symptoms, PRL/cortisol if indicated.

Additive GH/IGF-1 axis stimulation. Avoid in active malignancy, proliferative retinopathy, uncontrolled diabetes, pregnancy, and untreated pituitary/adrenal disorders. Grade C/D.

Synergy model · combo

GHRH-analog + GHRP-2 pairing concept

Component	Receptor	Contribution	Grade
GHRP-2	GHSR-1a (Gq/11)	Agonism + somatostatin withdrawal	B (acute GH)
CJC-1295 / sermorelin	GHRH-R (Gs–cAMP)	GHRH-arm amplification	C/D (combo)
Net effect	Convergent somatotroph	Supra-additive GH pulse	C/D

Titration logic · combo

Combination safety triggers

Trigger	Action	Rationale
IGF-1 above age range	Stop escalation	Additive GH/IGF-1 stimulation
Edema / BP / glucose worsening	De-escalate	GH-axis adverse pattern compounded
PRL / cortisol symptoms	Hold	GHRP-2 non-selectivity
Active malignancy / pregnancy	Hard stop	Proliferative / fetal concern

Biomarker scaffold · combo

Combination monitoring scaffold (none validated)

Marker	Why monitor	Validated?
IGF-1	Additive downstream exposure	No
Fasting glucose / A1c	Compounded insulin-resistance risk	No
Blood pressure / edema	Fluid-retention surveillance	No
PRL / cortisol	GHRP-2 non-selectivity	No
Sleep-apnea symptoms	GH-axis soft-tissue concern	No

L2 · Reconstitution & dose math

Reconstitution & Dose Calculator

For reference only. Not medical dosing advice. The Japanese diagnostic product is a 100 µg vial reconstituted in 10 mL saline; research-vial calculations below are educational modeling. Verify peptide purity, sterility, and storage; only use product from a licensed source.

Vial size (mg)

BAC water (mL)

Target dose (µg)

Concentration

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Draw volume
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Units (U-100)

—

Doses per vial

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Basis

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04 · Combination protocols

Stacking GHRP-2.

GHRP-2 is not FDA-approved and no formal combination clinical-trial data exist. The pairings below reflect mechanistic complementarity, anti-doping/endocrine literature, and observed practice patterns. None are FDA-validated combinations. Combination use of investigational compounds requires physician oversight, and GHRP-2 is WADA-prohibited for athletes.

GHRP-2 CJC-1295 (no DAC) Sermorelin

The signature GH-secretagogue pairing. GHRP-2 drives GH through GHSR-1a plus somatostatin withdrawal; a GHRH analog drives the parallel Gs–cAMP arm. Co-administration produces a GH pulse markedly larger than either agent alone. Additive GH/IGF-1 axis stimulation is the core caution — monitor IGF-1, glucose, edema. Not an approved protocol.

Component	Arm	Evidence
GHRP-2	GHSR-1a + SST↓	B (acute GH)
CJC-1295 / sermorelin	GHRH-R	C/D (combo)

GHRP-2 Sleep hygiene Resistance training

Endogenous GH pulses are sleep- and exercise-sensitive. Non-drug optimization (consistent sleep, progressive resistance training, adequate protein) may reduce any rationale for pharmacologic escalation. Do not infer peptide efficacy from lifestyle evidence — these are independent levers on the same axis. Grade D for the pairing as a "stack."

Lever	GH-axis effect	Grade
Slow-wave sleep	Largest physiologic GH pulse	A (physiology)
Resistance training	Exercise-induced GH/IGF-1	A (physiology)
GHRP-2 add-on	Pharmacologic pulse	D (combination)

GHRP-2 Nutrition support Cachexia care

Ghrelin-like appetite signaling makes GHRP-2 biologically plausible as an appetite adjunct in wasting contexts, and acute human appetite data exist. GHRP-2 acutely increased food intake in healthy men. Use caution in obesity, binge-eating, insulin resistance, and uncontrolled diabetes, where appetite stimulation is a liability. Grade B/D.

Context	Direction	Grade
Cachexia / wasting	Potential benefit	B/D
Obesity / IR	Liability	D (avoid)

GHRP-2 IGF-1 panel Glucose / A1c

Not a pharmacologic "stack" but a required safety overlay for any GH-secretagogue page. Track IGF-1, fasting glucose/A1c, BP, and edema. Biomarkers are not validated dosing controls for non-approved GHRP-2 protocols — they are risk monitors, not efficacy targets. Grade D.

Marker	Role	Validated?
IGF-1	Exposure / over-stimulation	No
Glucose / A1c	Insulin-resistance risk	No

GHRP-2 Ipamorelin

Often discussed as alternatives rather than a stack. Ipamorelin is positioned as more GH-selective with less PRL/cortisol and minimal appetite effect, at the cost of lower peak GH. Ipamorelin releases GH without significant ACTH/cortisol/PRL even at high doses, unlike GHRP-2. GHRP-2 produces higher peak GH; ipamorelin offers a cleaner endocrine profile. Combining two GHSR-1a agonists is redundant and not recommended.

Trait	GHRP-2	Ipamorelin
Peak GH	Highest	Moderate
PRL/cortisol	Moderate ↑	Minimal
Appetite	Moderate ↑	Minimal

Active malignancy Pregnancy WADA testing

Avoid any GH-axis stimulation stack in active malignancy, unexplained masses, proliferative retinopathy, uncontrolled diabetes, pregnancy, untreated pituitary/adrenal disease, or in WADA-tested athletes. GHRP-2 is prohibited at all times in sport. These are absolute stop conditions regardless of partner agent.

Condition	Status
Active malignancy / pregnancy	Absolute avoid
WADA-tested athlete	Prohibited

GHRP-2 CGM / glucose Diet structure

Because GH-axis stimulation opposes insulin action, any GHRP-2 use benefits from explicit glycemic co-management rather than a peptide partner. Continuous glucose monitoring or periodic A1c, paired with carbohydrate-aware meal timing, is the rational overlay — especially given GHRP-2's appetite stimulation. Not a pharmacologic stack; Grade D as a "protocol."

Lever	Purpose	Grade
CGM / A1c	Catch insulin-resistance drift	D
Meal timing	Offset appetite effect	D

GHRP-2 GH-stimulation testing

In its approved Japanese context, GHRP-2 functions as a safer provocative GH-stimulation agent than the insulin tolerance test (ITT), which carries hypoglycemia risk. This is the one "combination" with regulatory grounding — GHRP-2 substituting into a diagnostic workflow, not stacked with another secretagogue. Diagnostic label context. Grade B (diagnostic only).

Test	Risk	Grade
ITT	Hypoglycemia	A (legacy)
GHRP-2 stimulation	Lower acute risk	B (Dx)

Clinical note — GHRP-2's strongest combination rationale is mechanistic synergy with GHRH analogs, but this is exactly where additive GH/IGF-1 stimulation magnifies edema, glucose, and proliferative concerns. No combination has FDA validation; the safest "stack" is a robust monitoring overlay (IGF-1, glucose/A1c, BP, sleep symptoms) layered onto physician-supervised, time-limited use.

05 · Safety & contraindications

Safety profile & contraindications.

GHRP-2's safety signal is dominated by its non-selectivity (PRL/ACTH/cortisol co-release), ghrelin-type appetite stimulation, and the general GH-axis adverse pattern (insulin resistance, edema, carpal-tunnel symptoms). The Japanese diagnostic label is a single supervised dose; repeated/chronic exposure is unstudied for long-term safety.

Observed adverse / endocrine effects (human studies + label context)

Acute GH increaseThe intended pharmacodynamic effect. Robust, time-locked GH pulse after IV and SC dosing. Grade B.

Prolactin (PRL) increaseDocumented in human comparative endocrine studies. Monitor in symptomatic users. Grade B.

ACTH / cortisol increaseGHRP-2 raised ACTH and cortisol alongside GH; in rats the ACTH-releasing activity of KP-102 is mediated mainly by CRF release. Anxiety/insomnia/high-cortisol symptoms warrant de-escalation. Grade B.

Appetite / food-intake increaseAcute ghrelin-like appetite stimulation in healthy men. Moderate; relevant for glycemic and weight goals. Grade B.

Insulin resistance / hyperglycemiaMechanism-derived: GH-axis stimulation opposes insulin action. Monitor glucose/A1c.

Edema / paresthesia / carpal-tunnelClassic GH/IGF-1 fluid-and-tissue adverse pattern at higher exposure.

Injection / test-related symptomsDiagnostic label requires a supervised setting. Transient.

Anti-doping detectionGHRP-2 and metabolites are detectable in urine by LC/MS; prohibited at all times.

Sleep-apnea worseningGH-axis soft-tissue/fluid effects may aggravate airway symptoms.

Monitoring scaffold

Baseline

IGF-1, fasting glucose, HbA1c, fasting insulin (HOMA-IR), lipid panel, BP, weight/waist. PRL and morning cortisol/ACTH if baseline risk. Pregnancy test if reproductive potential. Pituitary imaging if a mass is suspected. Document WADA status for athletes.

During use

BP and edema each check-in; glucose/A1c at 8–12 weeks; appetite, weight, and sleep-apnea symptoms; PRL/cortisol if symptomatic. Hold for IGF-1 above age-adjusted range. None of these thresholds is validated specifically for non-approved GHRP-2 protocols.

Stop / escalate triggers

Hard-stop on pregnancy, active malignancy/unexplained mass, or WADA-tested status. De-escalate on worsening glucose, new edema/carpal-tunnel, sleep-apnea worsening, or PRL/cortisol symptoms. Diagnostic GH-stimulation result is the only validated endpoint, and only in the testing context.

Contraindications & cautions

Condition	Concern	Severity · grade
Pregnancy / possible pregnancy	Japanese label contraindication; animal/fetal-growth concern via GH/IGF-1 axis	Absolute
Active malignancy	IGF-1 is a growth/survival pathway; theoretical proliferative risk	Absolute / specialist-only
Unexplained pituitary mass	Endocrine stimulation risk	High
Uncontrolled diabetes	GH-axis insulin resistance	High
Proliferative diabetic retinopathy	Growth-factor concern	High
Untreated severe sleep apnea	Potential worsening from fluid/tissue effects	High
Hyperprolactinemia / prolactinoma	PRL-increase concern	High
Cushing's syndrome / adrenal disorder	ACTH/cortisol-axis concern	High
Competitive sport under WADA	Prohibited at all times	Absolute
Pediatric non-diagnostic use	Growth-axis manipulation outside diagnosis	High / specialist-only
Obesity / binge-eating	Appetite stimulation liability	Caution
Pre-diabetes / insulin resistance	Glycemic worsening	Caution
Severe renal / hepatic impairment	Altered clearance; limited data	Caution
Concurrent corticosteroids	Compounded HPA-axis effects	Caution
Non-sterile / unverified product	Compounding / endotoxin risk	Avoid
Thyroid disorder (untreated)	GH-axis interacts with thyroid hormone economy	Monitor
Cardiac failure / fluid-sensitive states	GH-axis fluid retention	Caution
Carpal tunnel / peripheral neuropathy history	GH/IGF-1 fluid-tissue effects may worsen symptoms	Monitor
Adolescents with open growth plates (non-Dx)	Growth-axis manipulation outside diagnosis	Avoid
Polypharmacy with HPA-active agents	Compounded ACTH/cortisol effects	Monitor
Acromegaly / prior GH excess	Further GH stimulation contraindicated	Avoid

06 · Trials & evidence base

What the evidence actually shows.

GHRP-2 has a stronger human pharmacodynamic base than many research peptides — formal Japanese diagnostic approval plus multiple human endocrine challenge studies. But the evidence is narrow: it supports acute GH stimulation and diagnostic testing far better than chronic wellness, body-composition, or performance use.

Discovery · 1980s

Bowers

Cyril Y. Bowers' group develops the GHRP series; KP-102/GHRP-2 emerges as a potent, specific GH-releasing hexapeptide. PMDA/development record.

Human PK/PD · 1998

n=10

Pihoker pediatric IV study (1 µg/kg): GH Cmax ≈ 50.7 ng/mL, Tmax ≈ 0.42 h, GHRP-2 t½β ≈ 0.55 h. The firmest quantitative anchor.

Human SC · 1998

5 days

Nijland: 100 µg SC daily ×5 days specifically stimulated GH; IGF-1 effect limited over the short course. Frequency/exposure govern downstream effect.

Diagnostic approval · 2004

Japan

Pralmorelin approved in Japan as GHRP Kaken 100 for GH-deficiency diagnosis — the only GHRP with regulatory approval anywhere. Label PMDA review document.

BHuman PK/PD · IV · pediatric

Pihoker et al. 1998 — PK/PD of GHRP-2, phase I in children

Ten prepubertal children given 1 µg/kg IV. Biexponential disposition; GHRP-2 t½β 0.55 h; GH Cmax 50.7 ng/mL at Tmax 0.42 h; EC₅₀ ≈ 1.09 ng/mL. The best-cited quantitative human anchor for GHRP-2.

PMID 9543135

BHuman · SC short course

Nijland et al. 1998 — 5-day SC GHRP-2 in healthy men

100 µg SC once daily ×5 days specifically stimulated GH release in man; response persisted with some adaptation, and IGF-1 elevation was limited over the short course — the empirical basis for community SC dosing.

PMID 9820615

BHuman endocrine comparison

Arvat et al. 1997 — GHRP-2 vs hexarelin: GH, PRL, ACTH, cortisol

Comparative human study showing dose- and age-dependent GH release with concurrent increases in prolactin, ACTH and cortisol — the canonical demonstration of GHRP-2's non-selectivity.

PMID 9285939

BHuman mechanistic

Gondo et al. 2001 — GHRP-2 in GHRH-receptor–deficient subjects

11 GHRH-R mutation subjects + 8 controls challenged with GHRP-2; the response pattern dissected GHRH-dependent vs independent components, implicating hypothalamic contribution to GHRP-2 action.

JCEM 2001

BHuman appetite

Laferrère et al. 2005 — GHRP-2 increases food intake

In healthy men, acute GHRP-2 stimulated food intake like ghrelin, confirming engagement of the central ghrelin appetite pathway alongside the GH effect.

PMC2824650

B/DOfficial label · diagnostic

GHRP Kaken 100 — Japanese prescribing information

Regulatory diagnostic label: adults 100 µg IV fasting; pediatric 2 µg/kg capped at 100 µg; 100 µg vial reconstituted in 10 mL saline; pregnancy contraindicated. The single authoritative human-use document.

JAPIC label

PReceptor pharmacology

IUPHAR — pralmorelin ligand / ghrelin receptor

Authoritative receptor annotation classifying pralmorelin as a ghrelin/GHS-receptor (GHSR-1a) agonist, ligand 1092 in the Guide to Pharmacology.

IUPHAR 1092

P/CMechanistic review

Growth-hormone secretagogue receptor — review

GHSR is broadly expressed and mediates endocrine and metabolic actions; the review frames how GHSR-1a agonism translates into pituitary GH release and peripheral effects.

PMID 17983853

CAnimal · repeated dosing

Swine GHRP-2 ×10 days — frequency-dependent GH/IGF-1

Twice-daily GHRP-2 for 10 days influenced GH/IGF-1 dynamics and growth-performance measures, supporting that exposure frequency — not just dose — governs the downstream IGF-1 response.

AJAS 2003

B/DAnti-doping analytical

Thomas et al. — GHRP urinary metabolites by LC-MS/MS

Analytical detection of GHRP-2 and its metabolite in human urine, underpinning WADA enforcement and confirming systemic exposure after administration.

PMID 25869809

DDevelopment review

Pralmorelin (KP-102, GPA-748) — Drugs in R&D

Development review summarizing the KP-102 program — codes, oral-activity notes, and the diagnostic-agent trajectory that ended in Japanese approval.

PMID 15230633

CGeneral pharmacology

Furuta et al. 2004 — general pharmacology of KP-102 (GHRP-2)

Characterized the potent, specific GH-releasing profile of KP-102, including interaction with somatostatin tone and the GH-axis — supporting the somatostatin-suppression mechanism arm.

PMID 15646371

BHuman · graded-dose pediatric

Mericq et al. 1998 — graded-dose GHRP in GH-deficient children

Eight-month treatment with graded GHRP doses in GH-deficient children examined growth response and tolerability — a longer-exposure human dataset informing the diagnostic-to-therapeutic boundary.

PMID 9661606

CPharmacological characterization

Doi et al. 2004 — pharmacological characteristics of KP-102 (GHRP-2)

Formal characterization of KP-102/GHRP-2 as a potent GH-releasing peptide, documenting the dose-response, route behavior, and specificity profile that underlies the Japanese diagnostic product.

PMID 15646370

CMechanism · ACTH/CRF (animal)

Hirotani et al. 2005 — ACTH-releasing activity of KP-102 mediated by CRF

In rats, GHRP-2's ACTH-releasing activity was shown to be mediated mainly by CRF release, clarifying the hypothalamic route of the HPA-axis (ACTH/cortisol) co-activation seen in human studies.

PMID 15645295

PComparator · selectivity

Raun et al. 1998 — ipamorelin, the first selective GH secretagogue

Characterized ipamorelin as releasing GH with GHRH-like selectivity and, in contrast to GHRP-2, no significant ACTH/cortisol/prolactin elevation even at >200× the GH-effective dose — the benchmark for GHRP-2's non-selectivity.

PMID 9849822

DHistory · discovery

Bowers / Tulane — origin of the GHRP series (1976→)

Cyril Bowers (Tulane) observed that enkephalin-amide analogs released GH from pituitary cells in 1976; pralmorelin emerged as a hexapeptide more potent than prior GHRPs and active even with somatostatin present, foreshadowing the later discovery of ghrelin.

Ishida 2020 review

GRADE summary — GHRP-2 earns Grade B for acute GH stimulation (multiple consistent human PK/PD and endocrine studies) and a Japanese diagnostic approval. Evidence is thin-to-absent (Grade C/D) for chronic wellness, body-composition, anti-aging, and performance use: long-term outcomes, optimal non-diagnostic route, chronic safety, validated monitoring thresholds, and disease-specific benefit/risk are all insufficient. The honest positioning is "diagnostic GH secretagogue with human PD evidence; non-diagnostic protocols speculative and higher-risk than selective alternatives."

07 · Compare & contrast

GHRP-2 vs the secretagogue field.

GHRP-2 sits in the middle of the GH-secretagogue selectivity spectrum: more potent (higher peak GH) than the others, but less GH-selective than ipamorelin and less appetite-driving than GHRP-6. Macimorelin is the only FDA-approved comparator (oral diagnostic).

Agent	Mechanism class	Primary use	Route	Human evidence	Status
GHRP-2 / pralmorelin	Ghrelin / GHSR-1a agonist	GH-stimulation diagnostic; research secretagogue	IV (Dx) · SC research	Human PD + Japan diagnostic approval	Japan diagnostic; not FDA; WADA-banned
GHRP-6	Ghrelin / GHSR-1a agonist	GH secretagogue; strong appetite	IV/SC/intranasal research	Human/animal PD; no formal approval	Not FDA; WADA-banned
Ipamorelin	Ghrelin / GHSR-1a agonist (selective)	GH secretagogue, cleaner profile	SC research/practice	Human/animal PD; compounding discussion	Not FDA; WADA-banned
Hexarelin	Ghrelin / GHSR-1a agonist (potent)	GH secretagogue; strong adrenal-axis	IV/SC research	Human PD; stronger ACTH/cortisol	Not FDA; WADA-banned
Sermorelin	GHRH-receptor agonist	GH stimulation	SC	Traditional endocrine use history	US discontinued product; compounding varies
CJC-1295	GHRH analog	GH-axis amplification (research)	SC research	PK studies; synergistic with GHRPs	Not FDA; WADA-banned
Macimorelin	Oral ghrelin-receptor agonist	Adult GHD diagnostic test	Oral	FDA-approved diagnostic use	FDA-approved (Dx); WADA-relevant for athletes

Related peptides.

09 · Reading-layer ledes

The same molecule, three depths.

L1 · Consumer — GHRP-2 (pralmorelin) is a synthetic peptide that triggers a short burst of growth-hormone release. Its strongest legitimate use is a diagnostic test of growth-hormone function — not general wellness or performance enhancement. It is approved only in Japan (for that test), is not FDA-approved, and is banned in sport.

L2 · Clinical — A ghrelin/GHSR-1a agonist and GH secretagogue with human pharmacodynamic evidence of acute GH release after IV and SC exposure, approved in Japan as a single-dose diagnostic agent for GH-deficiency assessment. Non-diagnostic dosing is experimental and demands careful endocrine-risk framing (PRL/ACTH/cortisol, glucose, appetite, edema), with pregnancy and active malignancy as hard stops.

L3 · Research — Pralmorelin is a met-enkephalin–derived synthetic hexapeptide, D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂, activating GHSR-1a (Gq/11–PLC–Ca²⁺) and converging with GHRH-receptor (Gs–cAMP) signaling while withdrawing somatostatin tone — a triple drive yielding the highest peak GH of classic GHRPs. Its downstream signature includes GH-pulse amplification and route/dose/frequency-dependent PRL, ACTH, cortisol, appetite, and IGF-1 effects.

08 · References & evidence

Source register.

Evidence grades reflect the strength of support for the specific claim cited, not the prestige of the journal. GHRP-2's human pharmacodynamic and diagnostic-label sources are its firmest evidence; mechanistic, animal, and detection-science sources support specific mechanism and safety claims.

A · RCT / regulatory approval

B · Human PK/PD / consistent clinical study

C · Animal / exploratory

D · Database / regulatory / practice-pattern

P · Mechanistic / preclinical pharmacology

Explore the ATLAS index

GHRP-2pralmorelin · diagnostic GH secretagogue

What GHRP-2 is — and what it is not.

How GHRP-2 drives a growth-hormone pulse.

1 · GHSR-1a / ghrelin receptor agonism

2 · Pituitary GH pulse amplification

3 · Hypothalamic GHRH facilitation

4 · Somatostatin suppression (GH-brake withdrawal)

5 · Appetite / feeding-behavior signaling

6 · ACTH / cortisol / PRL co-activation & IGF-1 downstream

Route-specific dosing models.

Reconstitution & Dose Calculator

Stacking GHRP-2.

Safety profile & contraindications.

Monitoring scaffold

Contraindications & cautions

What the evidence actually shows.

Pihoker et al. 1998 — PK/PD of GHRP-2, phase I in children

Nijland et al. 1998 — 5-day SC GHRP-2 in healthy men

Arvat et al. 1997 — GHRP-2 vs hexarelin: GH, PRL, ACTH, cortisol

Gondo et al. 2001 — GHRP-2 in GHRH-receptor–deficient subjects

Laferrère et al. 2005 — GHRP-2 increases food intake

GHRP Kaken 100 — Japanese prescribing information

IUPHAR — pralmorelin ligand / ghrelin receptor

Growth-hormone secretagogue receptor — review

Swine GHRP-2 ×10 days — frequency-dependent GH/IGF-1

Thomas et al. — GHRP urinary metabolites by LC-MS/MS

Pralmorelin (KP-102, GPA-748) — Drugs in R&D

Furuta et al. 2004 — general pharmacology of KP-102 (GHRP-2)

Mericq et al. 1998 — graded-dose GHRP in GH-deficient children

Doi et al. 2004 — pharmacological characteristics of KP-102 (GHRP-2)

Hirotani et al. 2005 — ACTH-releasing activity of KP-102 mediated by CRF

Raun et al. 1998 — ipamorelin, the first selective GH secretagogue

Bowers / Tulane — origin of the GHRP series (1976→)

GHRP-2 vs the secretagogue field.

Related peptides.

The same molecule, three depths.

Source register.

More GH Axis peptides & tools.