Ipamorelin: Complete Guide — Benefits, Dosage, Side Effects & Research

What Is Ipamorelin?

Ipamorelin is a synthetic pentapeptide (five amino acids) that acts as a selective growth hormone secretagogue (GHS) — meaning it stimulates the pituitary gland to release growth hormone (GH). It belongs to the growth hormone-releasing peptide (GHRP) family, which mimics the action of ghrelin by binding to the GHS-R1a receptor (growth hormone secretagogue receptor).

What sets Ipamorelin apart from other GHRPs (GHRP-2, GHRP-6, Hexarelin) is its selectivity. Ipamorelin stimulates GH release with minimal impact on other hormones — specifically, it does not significantly raise cortisol, prolactin, or ACTH levels at standard doses. This selectivity makes it one of the cleanest GH secretagogues available (Raun et al., 1998).

Developed by Novo Nordisk in the 1990s, Ipamorelin reached Phase II clinical trials for post-operative ileus (delayed gut recovery after surgery) but was not commercialized. It has since become one of the most popular peptides in the anti-aging and performance optimization community.

How Does Ipamorelin Work? (Mechanism of Action)

GHS-R1a Receptor Binding

Ipamorelin binds to the ghrelin receptor (GHS-R1a) on pituitary somatotroph cells. This receptor activation triggers a signaling cascade involving:

1. Phospholipase C activation
2. Inositol triphosphate (IP3) production
3. Intracellular calcium release
4. GH vesicle exocytosis

The result: a pulsatile release of GH that mimics (but amplifies) the body’s natural GH secretion pattern.

Selective GH Release

The key pharmacological advantage of Ipamorelin is dose-dependent specificity:

• At standard doses (1 μg/kg), it produces a robust GH pulse with no measurable increase in cortisol, prolactin, or ACTH
• This selectivity distinguishes it from GHRP-6 (which raises cortisol and provokes intense hunger) and GHRP-2 (which can elevate cortisol and prolactin)
• Even at supratherapeutic doses, Ipamorelin’s cortisol-raising effect is minimal compared to other GHRPs (Raun et al., 1998)

GH Pulsatility Preservation

Unlike exogenous GH injection (which creates a supraphysiological, non-pulsatile GH spike), Ipamorelin works with the body’s feedback system. The GH release triggered by Ipamorelin is still subject to somatostatin (GHIH) inhibition, meaning:

• GH pulses remain physiological in shape
• Negative feedback mechanisms are preserved
• The risk of GH-related side effects is theoretically lower than with exogenous GH

Synergy with GHRH Analogs

Ipamorelin’s mechanism (ghrelin mimicry) is distinct from GHRH analogs like CJC-1295 and Sermorelin (which act on GHRH receptors). These two pathways converge synergistically on pituitary somatotrophs — combining them produces a GH pulse significantly larger than either alone. This is the pharmacological basis for the popular CJC-1295 + Ipamorelin stack.

Research & Evidence

Growth Hormone Release (Human Studies)

In a Phase I study, intravenous Ipamorelin (0.01–1 μg/kg) produced dose-dependent GH release in healthy male volunteers. The GH response peaked approximately 40 minutes post-injection and returned to baseline within 2–3 hours. Notably, even at the highest dose tested, cortisol and prolactin remained unchanged from baseline (Hansen et al., 1999).

Comparative studies showed Ipamorelin produced GH release comparable to GHRP-6 at equivalent doses but with superior hormonal selectivity — no cortisol spike, no appetite stimulation, and no prolactin elevation.

Post-Operative Ileus (Clinical Trial)

The most advanced clinical application studied was post-operative ileus (POI) — the delayed return of gut motility after abdominal surgery. A Phase IIb trial (n=114) evaluated Ipamorelin infusion in patients following abdominal surgery. While results showed some promise for accelerating gut recovery, the clinical development was ultimately discontinued — not for safety concerns, but for commercial reasons (Greenwood-Van Meerveld et al., 2007).

Body Composition

Animal studies demonstrate that chronic Ipamorelin administration produces:

• Increased lean body mass
• Decreased fat mass
• Improved bone mineral density
• These effects are consistent with elevated GH/IGF-1 axis activation

A study in growth hormone-deficient swine showed that Ipamorelin (over 15 days) increased body weight gain with preferential lean mass accretion, supporting its potential for body composition improvement (Raun et al., 1998).

Bone Density

In ovariectomized rats (a model for postmenopausal osteoporosis), chronic Ipamorelin treatment increased bone mineral density and improved bone microarchitecture. The effect was dose-dependent and associated with elevated IGF-1 levels (Svensson et al., 2000).

Benefits (Based on Research and Community Reports)

• Clean GH release — stimulates GH without raising cortisol, prolactin, or ACTH
• Improved body composition — lean mass gain, fat mass reduction
• Better sleep quality — GH release during sleep is amplified; community reports consistently cite improved sleep
• Recovery enhancement — faster recovery from training and injury
• Anti-aging effects — improved skin quality, hair growth, general vitality (community-reported)
• Bone density support — preclinical evidence for improved bone health
• Minimal hunger increase — unlike GHRP-6, Ipamorelin does not significantly increase appetite

Dosage Protocols

⚠️ Disclaimer: Ipamorelin is not FDA-approved for any human use. The following represents community-reported protocols extrapolated from clinical research. This is not medical advice.

Standard Protocol

• Dose: 200–300 mcg per injection
• Frequency: 1–3 times daily
• Timing:
  • Before bed (most popular — amplifies nocturnal GH pulse)
  • Morning fasted
  • Post-workout
• Cycle length: 8–12 weeks on, 4 weeks off (though some use continuously)

Combined with CJC-1295 (DAC)

When stacked with CJC-1295 w/ DAC (Drug Affinity Complex):

• Ipamorelin: 200–300 mcg at bedtime
• CJC-1295 w/ DAC: 2 mg once or twice per week
• The DAC-modified CJC-1295 provides sustained GHRH-level elevation while Ipamorelin amplifies GH pulses

Combined with CJC-1295 (no DAC) / Mod GRF 1-29

• Ipamorelin: 200–300 mcg
• Mod GRF 1-29: 100–200 mcg
• Both at the same time: 2–3 times daily
• This combination produces synergistic GH release

Timing Considerations

• Fasted state: GH release is blunted by food (particularly carbohydrates and fats). Inject at least 2 hours after eating, or 30+ minutes before meals.
• Bedtime injection: The most popular timing, as it amplifies the natural nocturnal GH surge and improves sleep quality.
• Avoid with insulin spikes: Insulin is the primary inhibitor of GH release. Avoid injecting near carbohydrate-heavy meals.

Reconstitution

• Typically supplied as 2 mg or 5 mg lyophilized powder
• Reconstitute with bacteriostatic water
• Example: 5 mg + 2.5 mL BAC water = 2,000 mcg/mL → 0.15 mL = 300 mcg
• Refrigerate after reconstitution; use within 3–4 weeks

Side Effects & Safety

Common Side Effects

Ipamorelin has one of the mildest side effect profiles among GH secretagogues:

• Head rush or mild headache — typically transient, more common in early use
• Water retention — mild, dose-dependent (a GH class effect)
• Tingling or numbness in extremities — carpal tunnel-like symptoms at higher doses (GH effect)
• Injection site reactions — standard subcutaneous injection reactions
• Increased hunger — mild compared to GHRP-6, but some users notice it

Long-Term Considerations

• IGF-1 elevation: Chronic GH elevation raises IGF-1, which has both beneficial (anabolic, repair) and potentially concerning (cancer proliferation) implications. High IGF-1 levels are epidemiologically associated with increased cancer risk, though the causal relationship is complex.
• Insulin sensitivity: GH has anti-insulin effects. Prolonged use of any GH secretagogue can reduce insulin sensitivity, particularly at higher doses. Monitor fasting glucose and HbA1c.
• Pituitary desensitization: Theoretical concern with continuous use, though clinical evidence is limited. Cycling (8–12 weeks on, 4 weeks off) is the community standard to mitigate this.

What Ipamorelin Does NOT Do (vs. Other GHRPs)

• Does not cause significant cortisol release (unlike GHRP-6, GHRP-2)
• Does not cause significant prolactin elevation (unlike GHRP-2, Hexarelin)
• Does not cause intense appetite stimulation (unlike GHRP-6)
• Does not desensitize as quickly as Hexarelin

Stacking Options

• Ipamorelin + CJC-1295: The gold standard GH stack. Synergistic GH release through complementary pathways.
• Ipamorelin + BPC-157: Recovery stack. GH amplifies healing; BPC-157 targets local tissue repair.
• Ipamorelin + Sermorelin: Alternative GHRH + GHRP combination. Sermorelin has a shorter half-life than CJC-1295 but is FDA-approved for pediatric GH deficiency testing.

Legal Status

United States

Not FDA-approved for any human use. Available as a research chemical. Anti-aging clinics may prescribe Ipamorelin off-label, though this practice exists in a regulatory gray area. The FDA has issued guidance regarding compounded GH secretagogues.

Australia

Classified as Schedule 4 (prescription-only) by the TGA.

WADA

Prohibited under Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). GH secretagogues are explicitly banned in competitive sports.

Frequently Asked Questions

How is Ipamorelin different from HGH injections? Ipamorelin stimulates your pituitary to produce and release its own GH, preserving natural pulsatile patterns and feedback mechanisms. Exogenous HGH provides synthetic GH directly, bypassing the pituitary. Ipamorelin’s approach is generally considered more physiological and carries lower risk of side effects like acromegaly-like symptoms.

Will Ipamorelin make me hungry? Much less than GHRP-6. Ipamorelin’s selectivity means it doesn’t strongly activate ghrelin’s appetite-stimulating pathway. Some mild hunger increase is reported, but it’s typically manageable.

How long does it take to see results? Most users report improved sleep quality within the first week. Body composition changes (lean mass increase, fat loss) typically become noticeable over 4–8 weeks. Anti-aging effects (skin, hair, general vitality) develop over months of consistent use.

Can I take Ipamorelin long-term? The community standard is cycling (8–12 weeks on, 4 weeks off) to prevent pituitary desensitization and allow hormonal recalibration. Some users run it continuously with periodic blood work to monitor IGF-1 and metabolic markers.

Does Ipamorelin suppress natural GH production? Unlike exogenous GH, Ipamorelin does not suppress natural GH production because it works through the body’s own release mechanisms. The pituitary still produces GH — Ipamorelin just signals it to release more.

References

1. Raun K, et al. “Ipamorelin, the first selective growth hormone secretagogue.” Eur J Endocrinol. 1998;139(5):552-61. PubMed
2. Hansen BS, et al. “The growth hormone secretagogue ipamorelin: pharmacokinetics and pharmacodynamics in healthy volunteers.” Growth Horm IGF Res. 1999;9(5):313-9.
3. Greenwood-Van Meerveld B, et al. “The effect of ipamorelin, a ghrelin mimetic, on gastric and colonic motility in the dog.” Neurogastroenterol Motil. 2007;19(4):281-90. PubMed
4. Svensson J, et al. “Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure.” J Clin Endocrinol Metab. 1998;83(2):362-9. PubMed
5. 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.

Related Articles

Peptide

CJC-1295: Complete Guide — Benefits, Dosage, Side Effects & Research

Evidence-based breakdown of CJC-1295 — the GHRH analog that extends growth hormone releasing hormone activity. DAC vs no-DAC, dosing protocols, clinical research, and stacking with Ipamorelin.

Peptide

Sermorelin: Complete Guide — Benefits, Dosage, Side Effects & Research

Comprehensive evidence-based guide to Sermorelin — the GHRH analog with the longest clinical track record. Mechanism, FDA history, dosing, side effects, and comparison to CJC-1295.

Guide

Best Peptides for Muscle Growth & Recovery (2025 Guide)

Evidence-based guide to peptides for muscle growth, hypertrophy, and athletic recovery. GH secretagogues, healing peptides, and practical stacking protocols for lean mass gains.