Peptides: Ipamorelin Overview
Ipamorelin is the first selective growth hormone secretagogue with negligible cortisol and prolactin elevation at 100–300mcg doses. Evidence grade B from human pharmacokinetic studies.
| Measure | Value | Unit | Notes |
|---|---|---|---|
| Evidence Grade | B | grade | Multiple human pharmacokinetic studies confirm GH selectivity and safety profile (PMID 9849822); no large RCTs for body composition |
| Standard Dose | 200–300 | mcg/injection | 2–3× daily; typically combined with CJC-1295 no-DAC for maximum GH pulse; inject fasted |
| Half-life | ~2 | hours (subcut) | Longer half-life than GHRP-2 or GHRP-6 (~15–30 min); allows slightly more flexible injection timing |
| GH Pulse Onset | 15–30 | minutes post-injection | GH pulse measurable within 15–30 min; returns toward baseline within 2–3 hours; pulsatile pattern maintained |
| Cortisol Elevation | Minimal | at standard doses | Negligible cortisol elevation at 100–300mcg; distinguishing feature vs GHRP-2/6; Raun et al. confirmed selectivity (PMID 9849822) |
| Prolactin Elevation | Minimal | at standard doses | Prolactin elevation negligible at standard doses; mild at very high doses (>1mg); not a practical concern at 200–300mcg |
| Sequence | Aib-His-D-2-Nal-D-Phe-Lys-NH2 | pentapeptide | 5 amino acid pentapeptide; alpha-aminoisobutyric acid (Aib) at position 1 confers protease resistance |
Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH2) is a synthetic pentapeptide GHSR agonist first characterized by Raun et al. in 1998 (PMID 9849822). It was described in that foundational paper as “the first selective growth hormone secretagogue” — selective in the specific sense that it stimulates GH release without the cortisol, prolactin, and appetite side effects that characterize earlier GHRPs. This selectivity profile makes ipamorelin the preferred starting point for most practitioners approaching GH peptide protocols.
The Aib (alpha-aminoisobutyric acid) residue at position 1 confers protease resistance, contributing to ipamorelin’s longer effective half-life (~2 hours subcut) compared to GHRP-2 and GHRP-6 (~15–30 minutes). This longer window provides slightly more flexibility in injection timing while still producing discrete, pulsatile GH pulses.
Selectivity Comparison: Ipamorelin vs Other GH Secretagogues
| Effect | Ipamorelin | GHRP-2 | GHRP-6 | MK-677 (oral) |
|---|---|---|---|---|
| GH stimulation | Strong — ~3–4× baseline at 200mcg | Strong — ~4–5× baseline at 100mcg | Strong — ~4–5× baseline at 100mcg | Strong — 40–100% IGF-1 increase |
| Cortisol increase | Minimal at ≤300mcg | Mild; dose-dependent above 200mcg | Mild; dose-dependent above 200mcg | Mild-moderate; reported in some studies |
| Prolactin increase | Minimal at ≤300mcg | Mild; dose-dependent | Mild; dose-dependent | Mild |
| Hunger stimulation | Minimal | Mild | Strong — significant at all doses | Strong — persistent; major side effect |
| Water retention | Mild | Moderate | Moderate | Significant; common side effect |
| Cost-per-dose | Moderate | Low-moderate | Low-moderate | High (oral bioavailable) |
| Evidence grade | B | B | B | B |
| Oral availability | No — injection only | No — injection only | No — injection only | Yes — oral |
Dosing Protocol
Standard ipamorelin protocol:
- Dose: 200–300mcg per injection
- Frequency: 2–3× daily; typically morning fasted + pre-sleep; optionally pre-workout fasted
- Route: Subcutaneous injection; abdomen preferred
- Combination: CJC-1295 no-DAC 100–200mcg simultaneously (same injection session, separate syringe)
- Cycle: 12 weeks on / 4 weeks minimum off
Ipamorelin’s 2-hour half-life (vs 30 minutes for most GHRPs) means the window between injection and meal/post-workout carbohydrates is more forgiving than with GHRP-2 or GHRP-6.
Why the Selective Profile Matters
The cortisol and prolactin elevation associated with GHRP-2 and GHRP-6 at higher doses represent genuine physiological trade-offs. Chronically elevated cortisol can:
- Promote muscle catabolism
- Worsen insulin sensitivity
- Impair sleep quality
- Blunt the anabolic effects of GH/IGF-1
Ipamorelin’s negligible HPA axis activation at standard doses (PMID 9849822) means users achieve GH pulse amplification without these cortisol-mediated counter-effects — directly improving the net anabolic balance.
Legal Status
| Jurisdiction | Status | Schedule | Notes |
|---|---|---|---|
| USA | Research chemical | Unscheduled | Not FDA-approved; WADA prohibited (S2) for competitive athletes |
| UK | Not scheduled | None | Legal to possess; WADA prohibited under UKAD anti-doping rules |
| Australia | Prescription restricted | Schedule 4 (TGA) | ASADA prohibited; not commercially available without prescription |
| Canada | Gray market | No schedule | No approved DIN; WADA prohibited for athletes |
| EU | Generally unscheduled | Varies by country | No EMA approval; WADA prohibited for athletes |
Related Pages
Sources
- Raun K et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-61. PMID 9849822
- Johansen PB et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999;9(2):106-13. PMID 10373343
Frequently Asked Questions
Why is ipamorelin considered the cleanest GH secretagogue?
Ipamorelin's selectivity comes from its structural design: it activates GHSR-1a for GH release with minimal stimulation of the orexigenic (appetite) pathway and negligible HPA axis activation. In Raun et al. 1998 (PMID 9849822), ipamorelin was characterized as the first growth hormone secretagogue that does not stimulate cortisol or prolactin at GH-effective doses, distinguishing it clearly from GHRP-2, GHRP-6, and hexarelin.
What is the optimal injection timing for ipamorelin?
Pre-sleep injection is generally considered optimal, aligning with the largest natural GH pulse that occurs approximately 60 minutes after sleep onset during deep NREM sleep. Fasted morning (before breakfast) and pre-workout fasted state are secondary options. Food intake within 2 hours before injection blunts the GH response by 50–75% due to elevated insulin and somatostatin tone.
Should ipamorelin be used alone or combined with CJC-1295?
Ipamorelin can be used as a standalone GH secretagogue, but combining it with CJC-1295 no-DAC (injected simultaneously) produces approximately 3–4× greater GH pulse amplitude by simultaneously stimulating GHSR (ipamorelin) and GHRH-R (CJC-1295) — two different receptors on pituitary somatotrophs. The ipamorelin + CJC-1295 no-DAC combination is the most commonly used GH peptide stack and is considered more effective than either alone.