GHRP-2: Complete Guide

GHRP-2 (D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2) was one of the first synthetic GH secretagogues developed, emerging from Cyril Bowers' pioneering work at Tulane University in the 1980s. Bowers and colleagues discovered that certain modified met-enkephalin derivatives could specifically stimulate GH release from pituitary cells — a finding that opened an entirely new pharmacological pathway for GH regulation, distinct from the known GHRH/somatostatin axis (Bowers et al., 1984).

GHRP-2 was synthesized and optimized as part of the effort to develop potent, selective GH secretagogues. It proved to be the most effective GH releaser of the peptidyl GHS series, producing larger and more sustained GH pulses than its predecessors GHRP-6 and GHRP-1. The research on GHRP-2 and its relatives was instrumental in characterizing the ghrelin receptor (GHSR-1a) — the orphan receptor that GHRPs were found to activate, which ultimately led to the discovery of ghrelin itself in 1999 by Kojima et al.

GHRP-2 has been approved in Japan under the name pralmorelin (marketed as GHRP Kaken) as a diagnostic agent for GH deficiency. A 100 mcg IV injection followed by serial GH measurements can differentiate between GH-deficient and GH-sufficient patients. This regulatory approval — though limited to diagnostic use — provides a level of clinical safety validation unusual for research peptides.

GHRP-2 activates GHSR-1a (growth hormone secretagogue receptor 1a) on pituitary somatotrophs, triggering GH release through a pathway complementary to GHRH. Understanding both pathways is essential for optimizing GH release:

• GH release via GHSR-1a: GHRP-2 binds ghrelin receptors on pituitary somatotrophs, depolarizing the cell membrane through a PLC/IP3/PKC-mediated calcium influx pathway. This produces dose-dependent GH pulses — larger in amplitude than those from ipamorelin, GHRP-6, or hexarelin at equivalent doses
• Synergy with GHRH: GHRH (or its analogs CJC-1295 and sermorelin) activates GHRH receptors via a cAMP/PKA pathway. Because GHRP-2 and GHRH act through different second messenger systems, their combined effect on GH release is synergistic — exceeding the sum of individual effects. Arvat et al. (2001) demonstrated that GHRP + GHRH co-administration produced GH peaks 2–3x greater than either alone
• ACTH/cortisol stimulation: GHRP-2 activates hypothalamic pathways that increase ACTH release, consequently elevating cortisol. This effect is more pronounced than with ipamorelin but less dramatic than with GHRP-6
• Prolactin elevation: Increases prolactin secretion through a mechanism not fully characterized but likely involving tuberoinfundibular dopaminergic pathway modulation. This is one of the key selectivity disadvantages versus ipamorelin
• Appetite stimulation: GHSR-1a activation in hypothalamic appetite centers produces moderate ghrelin-mimetic hunger — less intense than GHRP-6 but more noticeable than ipamorelin. Onset occurs within 20–30 minutes of injection

Choosing between GH secretagogues involves balancing potency against selectivity. GHRP-2 sits at the high-potency, lower-selectivity end of the spectrum:

For most GH optimization purposes, ipamorelin is preferred due to its clean side effect profile. GHRP-2 is chosen when maximum GH output is the priority and the user is willing to manage cortisol and prolactin elevation. GHRP-6 is preferred specifically when appetite stimulation is desired (hardgainers, bulking). Hexarelin offers the unique addition of cardiac benefits but desensitizes with chronic use.

Timing matters for GH secretagogues. Administer on an empty stomach — food, especially carbohydrates and fats, significantly blunts GH response by raising somatostatin and insulin. Optimal timing is upon waking (before breakfast), post-workout (if fasted), and before bedtime (at least 2 hours after last meal). The bedtime dose is often considered most important, as it amplifies the natural nocturnal GH pulse.

Use the peptide calculator for reconstitution. Typical reconstitution: add 2 mL bacteriostatic water to a 5 mg vial for 2.5 mg/mL concentration (100 mcg per 4 tick marks on a standard insulin syringe).

GHRP-2's side effect profile reflects its broader GHSR-1a activation compared to more selective agents like ipamorelin:

• Cortisol elevation: Clinically significant at higher doses. Chronic cortisol elevation can promote fat storage (particularly visceral), impair immune function, and interfere with sleep. Monitor cortisol levels if using GHRP-2 long-term, and consider limiting to 2 doses per day rather than 3
• Prolactin elevation: Can affect reproductive function, libido, and mood with chronic use. Men may experience reduced libido or nipple sensitivity; women may experience menstrual irregularities. Consider prolactin monitoring with extended use
• Appetite increase: Moderate hunger stimulation — less dramatic than GHRP-6 but noticeable within 20–30 minutes of injection. This may be beneficial for those in caloric surplus but counterproductive for fat loss goals
• Water retention: Related to GH elevation; typically mild. Manifests as slight puffiness, particularly in extremities
• Flushing and tingling: Common immediately after injection, typically lasting 5–10 minutes. Generally described as warmth or pins-and-needles sensation
• Injection site reactions: Mild redness and occasional itching at subcutaneous injection sites
• Numbness/tingling in extremities: Carpal tunnel-like symptoms possible with chronic GH elevation

• Fasted administration is critical: Elevated blood glucose and insulin suppress GH release. Wait at least 2 hours after eating before injecting. Eating immediately after injection (within 15–20 minutes) is acceptable as the GH pulse has already been initiated
• Storage: Lyophilized (powder) vials are stable at room temperature for weeks; refrigerated for months. Once reconstituted with bacteriostatic water, store at 2–8°C and use within 4–6 weeks
• Cycling considerations: Unlike hexarelin, GHRP-2 shows minimal receptor desensitization with continued use. Most research protocols run 8–12 week cycles, though some use it continuously for months. Periodic breaks may be advisable to normalize cortisol and prolactin
• Combining with GHRH analogs: The GHRP + GHRH combination is the standard approach in GH optimization research. GHRP-2 + CJC-1295 (no DAC) is the most popular high-potency stack. GHRP-2 + sermorelin is a common clinical combination. Do NOT combine two different GHRPs (e.g., GHRP-2 + GHRP-6), as they compete for the same receptor
• Anti-doping: GHRP-2 and its metabolites are detectable in urine testing. It is prohibited by WADA (World Anti-Doping Agency) under the S2 category (peptide hormones, growth factors)