GHRP-2 vs GHRP-6: Head-to-Head Comparison

GHRP-2 and GHRP-6 both activate the GHS-R1a (ghrelin receptor) to stimulate pituitary GH release, but their structural differences produce distinct pharmacological profiles.

GHRP-2: Maximum GH Potency

GHRP-2 (D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2) was developed as an optimization of earlier GHRPs, designed for maximal GH-releasing activity. It is widely considered the most potent GH secretagogue in the GHRP class:^[1]

• GH release: GHRP-2 produces the strongest GH release per dose among the classical GHRPs, inducing a robust GH pulse comparable to or exceeding GHRP-6.
• Ghrelin mimicry: As a synthetic ghrelin analog, GHRP-2 increases food intake in a manner similar to endogenous ghrelin, though the appetite effect is generally less intense than GHRP-6.^[2]
• Cortisol and prolactin: GHRP-2 produces moderate elevations in both ACTH/cortisol and prolactin, though research suggests its cortisol effects may be somewhat lower than GHRP-6’s.^[1]

GHRP-6: Potent GH Release with Maximum Appetite Effect

GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is one of the earliest synthetic GH secretagogues and remains widely studied for its GH-releasing and appetite-stimulating properties:^[3]

• GH release: GHRP-6 is a potent GH secretagogue, producing substantial acute GH elevation from pituitary somatotrophs, though slightly less than GHRP-2 at equivalent doses.
• Appetite stimulation: GHRP-6 produces the strongest appetite response among GHRPs, triggering pronounced hunger within 15–20 minutes of injection. Studies have shown significant increases in food intake following administration.
• Cortisol elevation: GHRP-6 significantly increases ACTH and cortisol levels, with cortisol effects that may exceed those of GHRP-2.^[1]
• Cardioprotection: Unique to GHRP-6, research has demonstrated cardioprotective effects mediated through CD36 receptors, independent of GH release.

Both peptides have been studied in human subjects, with some head-to-head comparisons available.

Comparative Hormonal Effects

Research by Arvat et al. directly compared the hormonal effects of GHRP-2, GHRP-6, and hexarelin in human subjects:^[1]

• GH release: GHRP-2 induced the strongest GH response among the peptides tested, exceeding the response to GHRH alone.
• ACTH and cortisol: Both GHRP-2 and GHRP-6 elevated ACTH and cortisol, with effects greater than those seen with GHRH. GHRP-6 tended to produce slightly higher cortisol responses.
• Prolactin: Both peptides elevated prolactin moderately, with comparable effects.

GHRP-2 Appetite Research

Studies by Laferrère et al. demonstrated that GHRP-2 infusion increased food intake by 35.9% compared to saline in healthy men, confirming its ghrelin-mimetic appetite-stimulating properties.^[2]

GHRP-6 Cardioprotective Research

Cuban research groups have extensively studied GHRP-6’s cardioprotective and cytoprotective effects. GHRP-6 demonstrated protective effects against ischemia-reperfusion injury in multiple organ systems, mediated through CD36 receptor activation rather than GH release.^[3]

GHRP-2 and GHRP-6 share similar dosing parameters, but their side effect profiles create different practical considerations.

Shared Dosing Parameters

• Dose range: 100–300 mcg subcutaneous injection, 1–3 times daily for both peptides.
• Saturation dose: Research suggests diminishing GH returns above approximately 100–200 mcg per injection for both compounds.
• Timing: Administered on an empty stomach, typically before bed, upon waking, and/or pre-workout.
• Combination use: Both are commonly combined with a GHRH analog (CJC-1295 or sermorelin) for synergistic GH release.

Practical Differences

• GHRP-2: The moderate appetite effect is more manageable than GHRP-6’s intense hunger, making it somewhat more practical for researchers on controlled diets.
• GHRP-6: The strong hunger response requires planning meals around injection timing and makes it impractical for fasting or caloric restriction protocols.
• Both: The cortisol and prolactin elevation with both peptides has led many researchers to prefer ipamorelin, which produces comparable GH release without these hormonal side effects.

Both GHRP-2 and GHRP-6 share a non-selective side effect profile that distinguishes them from newer, more selective GH secretagogues.

GHRP-2 Side Effects

• Appetite increase: Moderate hunger stimulation, less intense than GHRP-6 but still noticeable.
• Cortisol elevation: Moderate ACTH/cortisol increase that could become problematic with chronic use.
• Prolactin elevation: Moderate increase that may affect reproductive hormone balance with sustained use.
• Water retention: Consistent with GH-mediated fluid effects.
• Tingling/numbness: Transient paresthesias reported at higher doses.

GHRP-6 Side Effects

• Intense hunger: The most prominent side effect—pronounced appetite within 15–20 minutes that can be difficult to manage.
• Cortisol elevation: Significant ACTH/cortisol increase, potentially exceeding GHRP-2’s effect.^[1]
• Prolactin elevation: Comparable to GHRP-2.
• Water retention and tingling: Similar to GHRP-2.

Neither GHRP-2 nor GHRP-6 has undergone formal FDA safety review. Both have been largely superseded by ipamorelin for GH optimization research due to ipamorelin’s selective profile that avoids cortisol, prolactin, and appetite effects entirely.

While both peptides have been largely replaced by ipamorelin for general GH optimization, each retains specific research niches.

GHRP-2 May Be Preferred For:

• Maximum GH release: When the research goal is the highest possible acute GH pulse and cortisol/prolactin effects are acceptable trade-offs.
• Moderate appetite needs: When some appetite stimulation is acceptable or even desired, but the extreme hunger of GHRP-6 is not.
• Ghrelin-pathway research: As a ghrelin mimetic, GHRP-2 is useful for studying hunger signaling and energy homeostasis.

GHRP-6 May Be Preferred For:

• Appetite stimulation research: When increased food intake is a desired outcome—for muscle wasting, cachexia, or recovery from illness.
• Cardioprotection research: GHRP-6’s unique CD36-mediated cardioprotective effects are not shared by GHRP-2 or ipamorelin.
• Cytoprotection studies: The extensive Cuban research on GHRP-6’s protective effects against ischemia-reperfusion injury supports its use in cytoprotection research.
• Budget priority: GHRP-6 is typically the least expensive GH secretagogue available.

Consider Ipamorelin Instead

For most GH optimization research, ipamorelin has superseded both GHRP-2 and GHRP-6 due to its selective GH release without cortisol, prolactin, or appetite effects. Unless the specific non-selective properties of GHRP-2 or GHRP-6 are desirable for the research question, ipamorelin is generally the better-tolerated option.