Ipamorelin
The cleanest of the growth hormone-releasing peptides: a selective ghrelin-receptor agonist that triggers a natural GH pulse without spiking cortisol, prolactin, or ACTH.
Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) and selective growth hormone secretagogue that acts as a ghrelin receptor (GHS-R1a) agonist. Developed by Novo Nordisk in the late 1990s, its defining feature is selectivity: it stimulates pulsatile GH release with minimal effect on cortisol, prolactin, ACTH, LH, FSH, or TSH, unlike earlier GHRPs such as GHRP-2, GHRP-6, and hexarelin. It reached Phase 2 trials for postoperative ileus (via Helsinn/Sapphire) but was discontinued for lack of efficacy, and it has no FDA approval for any indication. It is most commonly researched paired with a GHRH analog such as CJC-1295 or sermorelin, whose complementary receptor pathway produces a substantially larger GH pulse than either agent alone.
Class
Synthetic pentapeptide (selective GH secretagogue / GHS-R1a agonist)
Half-life
~2 hours (plasma)
Routes
Subcutaneous, Intravenous (clinical research only)
Category
Growth Hormone & Performance
Researched benefits
What it's studied for
Selective GH release without stress-hormone burden
Ipamorelin stimulates dose-dependent GH secretion from pituitary somatotrophs while producing no significant elevation of cortisol, prolactin, ACTH, LH, FSH, or TSH, even at doses many times above the GH-releasing threshold. This selectivity, established in the original 1998 characterization, is the primary reason it is favored over less selective GHRPs.
Preserves natural pulsatile GH architecture
Because it clears in roughly 2 hours, each injection produces a discrete GH pulse that reabsorbs into the body's normal pulsatile rhythm, allowing somatostatin to suppress GH between pulses. This preserves negative feedback and avoids the tonic, non-pulsatile elevation of exogenous HGH.
IGF-1 elevation and body composition support
The acute GH pulse drives hepatic IGF-1 synthesis; consistent dosing (typically with a GHRH partner) raises steady-state IGF-1 roughly 30-80% over baseline within 2-4 weeks, supporting muscle protein synthesis, lipolysis, and modest lean-mass gain in hypogonadal adults. Human outcome data for body composition remain limited to mechanism and PK studies.
Improved slow-wave sleep and recovery
Because physiologic GH pulses occur during deep sleep, pre-bed dosing is reported to improve slow-wave sleep architecture and accelerate recovery between training sessions. Community reports frequently cite improved sleep onset and quality within the first nights.
Synergy with GHRH analogs
Ipamorelin (ghrelin receptor / Gq-11 pathway) and GHRH analogs like CJC-1295 or sermorelin (GHRH receptor / Gs-cAMP pathway) converge on the same somatotroph through distinct second messengers, producing a GH pulse 3-5x larger than either agent alone. This combination is the backbone of modern peptide-clinic GH protocols.
GI motility (the studied clinical indication)
Ghrelin-receptor activation accelerates gastric emptying, which is why ipamorelin was clinically developed for postoperative ileus. In the Phase 2 trial it was well tolerated and produced numerical improvement in time to first tolerated meal, though it did not meet its primary efficacy endpoint.
Mechanism
How it works
Ipamorelin acts as a selective agonist at the growth hormone secretagogue receptor 1a (GHS-R1a), the same Class A G-protein-coupled receptor activated by endogenous ghrelin. GHS-R1a is expressed on pituitary somatotrophs, hypothalamic arcuate-nucleus neurons, and at lower density on gastric cells, pancreatic islets, and cardiomyocytes. Ligand binding activates Gq/11, triggering phospholipase-C to cleave PIP2 into IP3 and DAG; IP3 mobilizes intracellular calcium while DAG activates PKC, depolarizing the somatotroph and driving rapid exocytosis of preformed GH granules. A detectable GH rise occurs within about 15 minutes and peaks at 30-60 minutes post-injection. Ipamorelin has an EC50 of roughly 1.3 nM at GHS-R1a, similar to native ghrelin.
The distinguishing property is selectivity. Earlier GHS peptides (hexarelin, GHRP-6, GHRP-2) also cross-react with adjacent receptors on corticotrophs and lactotrophs, producing cortisol, prolactin, and ACTH elevation. Ipamorelin, at doses far above its GH-releasing ED50 (reported as no measurable change even at 200x the effective dose), produces no significant rise in cortisol, prolactin, ACTH, LH, FSH, or TSH. This clean endocrine profile was the primary design objective and is why it can be used in longer protocols without compromising recovery, immune function, or sleep.
The standard research and clinical protocol pairs ipamorelin with a GHRH analog (most commonly MOD-GRF 1-29 / CJC-1295 without DAC, or sermorelin). The two pathways converge on the pituitary somatotroph through different second messengers: ipamorelin via GHS-R1a / Gq-11 / IP3-calcium, and the GHRH analog via GHRHR / Gs / cAMP-PKA-CREB. Dual activation produces a GH pulse roughly 3-5x larger than either agent alone and recruits a larger fraction of the somatotroph reserve, which is why nearly all protocols use the combination.
Downstream, the acute GH pulse stimulates hepatic IGF-1 synthesis (peaking around 24 hours post-dose), which drives muscle protein synthesis, cartilage deposition, and lipolysis. Because GHS-R1a extends beyond the pituitary, chronic administration also produces mild appetite increase (much less than native ghrelin given the short half-life), accelerated gastric emptying, and cardioprotective/anti-inflammatory signaling in some animal models.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Reconstitution
Standard: 5 mg lyophilized vial + 2 mL bacteriostatic water = 2.5 mg/mL (2500 mcg/mL). Inject the BAC water down the vial wall (not directly onto the powder), swirl gently for 10-15 seconds and let stand until clear and colorless in 1-2 minutes; never shake or vortex. At 2.5 mg/mL: 100 mcg = 0.04 mL (4 units), 200 mcg = 0.08 mL (8 units), 300 mcg = 0.12 mL (12 units) on a 1 mL insulin syringe. Label with the reconstitution date and refrigerate (2-8 C / 36-46 F); use within 30 days. Unreconstituted powder is stable 2+ years refrigerated. Do not freeze the reconstituted solution.
Beginner (standalone)
- Dose
- 200 mcg
- Frequency
- Once daily
- Timing
- Pre-bed, fasted (>=2 hours after last meal, no carbs before injection)
- Duration
- Weeks 1-4
- Route
- Subcutaneous (abdominal fat, rotate sites)
Goal is to learn the injection workflow and assess personal response before adding a stack partner. Do not exceed 200 mcg per injection, do not combine with a GHRH analog in week 1, and do not inject pre-workout or after meals. Track sleep quality, recovery, evening appetite, and any head-heaviness or injection-site reactions.
Intermediate (standard stack)
- Dose
- 200 mcg ipamorelin + 100 mcg MOD-GRF 1-29 (CJC-1295 without DAC)
- Frequency
- 1-2x daily
- Timing
- Pre-bed (within 30 min of lights-out) and/or morning fasted on waking
- Duration
- 8 weeks on / 4 weeks off
- Route
- Subcutaneous (both peptides can be drawn into the same syringe)
Exploits the GHRH x ghrelin synergy for maximal pulse amplitude. 1x daily pre-bed is the conservative sleep/recovery protocol; 2x daily (pre-bed + morning fasted) is the body-composition protocol with roughly 30% higher steady-state IGF-1 but more fluid retention. Reduce dose or stop if IGF-1 exceeds the age-adjusted upper limit, HbA1c rises >0.3 points in a cycle, or edema/carpal-tunnel symptoms appear.
Advanced (tri-daily stack)
- Dose
- 100-200 mcg ipamorelin + 100 mcg MOD-GRF 1-29 per injection
- Frequency
- 3x daily
- Timing
- Morning fasted, midday (fasted >=2h before lunch), and pre-bed
- Duration
- 8-12 weeks on / 4-6 weeks off
- Route
- Subcutaneous
For experienced users with baseline labs and longitudinal monitoring. Three pulses per day roughly mimic the natural 3-5 pulse/day adult GH rhythm. An alternative advanced configuration is 100 mcg ipamorelin + 2 mg tesamorelin once daily pre-bed for visceral-fat-focused goals. Long-term continuous dosing (>6 months) is not well characterized; monitor bloodwork monthly.
- Typical therapeutic range is 100-300 mcg subcutaneous per injection, 1-3 times daily; a flat 200 mcg dose (roughly 1-3 mcg/kg) suits most.
- Dose-response is roughly linear from ~50 to 300 mcg; above 300 mcg per injection GH pulse amplitude plateaus while side effects (fluid retention, hunger, paresthesias) rise. Run more frequent smaller pulses rather than larger single doses for higher total exposure.
- Fasted dosing is non-negotiable: elevated insulin raises somatostatin tone and can blunt the GH pulse by 50-70%. The two reliable fasted windows are pre-bed (2+ hours post-meal) and morning on waking.
- Alcohol independently suppresses GH; avoid within 4 hours of dosing. Caffeine does not interfere and may amplify the slow-wave-sleep effect.
- Cycling (commonly 8-12 weeks on / 4-6 weeks off) supports HPA axis integrity, insulin sensitivity recovery, and IGF-1 washout, even though ipamorelin does not produce the sustained receptor occupancy that drives tachyphylaxis.
- Recommended monitoring: baseline and periodic IGF-1, fasting glucose, HbA1c, and insulin; add testosterone, PSA (men >40), CBC, and a metabolic panel for stacked protocols.
Evidence
Research & clinical studies (4)
Ipamorelin, the first selective growth hormone secretagogue
Established dose-dependent GH release in swine and characterized ipamorelin's selectivity, showing no measurable change in cortisol, prolactin, FSH, LH, TSH, or ACTH even at 200x the GH-releasing dose.
Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients
In a Phase 2 trial (n=114), ipamorelin 0.03 mg/kg twice daily was well tolerated over 7 days with no serious adverse events and produced numerical improvement in time to first tolerated meal, though the primary efficacy endpoint was not statistically significant.
PMID 25331030Injectable Peptides in Sports Medicine: A Structured Narrative Review of Evidence, Safety, and Antidoping Implications
Concluded that ipamorelin, as a GH-axis secretagogue, remains investigational for musculoskeletal applications with uncertain safety, product-quality concerns, and antidoping restrictions, lacking sufficient clinical evidence for sports-medicine use.
PMID 42160466Therapeutic Peptides in Aesthetic, Metabolic and Endocrine Conditions: Effects, Safety, Clinical Applications, and Future Perspectives
Found that therapeutic peptides show promise for metabolic and endocrine conditions but emphasized that many novel peptides currently lack sufficient research data to support safe human use.
PMID 42123471Combinations
Stacking & blends
CJC-1295 + Ipamorelin (GH Optimization)
Amplified, physiologically natural GH release for body composition and recovery
Pairs a GHRH analog that extends the GHRH signal window with a selective ghrelin-receptor secretagogue; the two pathways converge on the somatotroph through distinct second messengers to produce a GH pulse 3-5x larger than either alone, with minimal cortisol or prolactin burden. This is the single most common peptide-clinic GH protocol.
CJC-1295 + Ipamorelin + BPC-157 (Recovery & GH)
Systemic anabolic support plus targeted tissue and injury repair
The GH-secretagogue synergy supports protein synthesis and systemic recovery while BPC-157 provides localized tendon, ligament, and gut healing, so athletes get both a systemic GH/IGF-1 signal and local repair simultaneously.
CJC-1295 + Ipamorelin + GHRP-6 (GH Secretagogue Max)
Maximal endogenous GH output
An advanced triple-secretagogue stack combining extended GHRH signaling, selective clean ghrelin-receptor stimulation, and additional pulse amplitude plus appetite stimulation from GHRP-6, aimed at the highest attainable GH output without exogenous HGH.
Tesamorelin + Ipamorelin
Visceral-fat-focused GH axis support
Tesamorelin is a stabilized GHRH analog with longer GHRH-receptor occupancy and a more durable GH pulse than MOD-GRF 1-29, giving a stronger effect on visceral adiposity when paired with ipamorelin's selective secretagogue action.
Ipamorelin + GLP-1 recomposition
Preserve lean mass during a GLP-1-induced caloric deficit
The ipamorelin + GHRH pulse maintains the GH/IGF-1 anabolic signal that supports lean mass while GLP-1 agonists drive fat loss; a common recomposition pairing. Monitor glucose, since both classes influence insulin sensitivity.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Active malignancy or cancer history (GH/IGF-1 are trophic factors)
- Known or suspected pituitary tumor / acromegaly
- Active diabetic retinopathy
- Pregnancy or breastfeeding
- Severe insulin resistance or uncontrolled type 2 diabetes
Ipamorelin has the cleanest side-effect profile of the GHRP class and, unlike GHRP-2/6 and hexarelin, does not elevate cortisol, prolactin, or ACTH. Most effects are dose-dependent and minimized by staying at or below 300 mcg per injection and cycling. At supraphysiological or chronically high doses, general GH-excess effects can appear: insulin resistance, carpal tunnel symptoms, and fluid retention. Long-term human safety has not been established through controlled trials; monitor IGF-1, fasting glucose, and HbA1c, and discontinue for persistent edema, worsening carpal tunnel, IGF-1 >300 ng/mL, rising glucose/HbA1c, any new mass or visual change, or severe headache.
FAQ
Ipamorelin — common questions
What makes ipamorelin different from GHRP-2 or GHRP-6?
Selectivity. Ipamorelin is the first and only GHS peptide clinically characterized as releasing growth hormone without elevating cortisol, prolactin, ACTH, LH, FSH, or TSH, even at doses far above the GH-releasing threshold. Earlier GHRPs cross-activate corticotrophs and lactotrophs, producing cortisol and prolactin spikes that compromise recovery and, in men, can affect breast tissue. This clean profile is why ipamorelin became the default GHS peptide.
Do I need to stack it with CJC-1295 or MOD-GRF 1-29?
Functionally, most protocols do. Ipamorelin alone produces a modest GH pulse; paired with a GHRH analog the pulse is roughly 3-5x larger because the two pathways converge on the somatotroph through different second messengers and recruit more of the GH reserve. Standalone ipamorelin is mainly used in the first few weeks to confirm tolerance before adding the GHRH partner.
What is the correct dose and how often should it be injected?
The typical range is 100-300 mcg subcutaneously per injection, 1-3 times daily. Common configurations are 200 mcg pre-bed once daily for sleep/recovery, or 200 mcg + 100 mcg MOD-GRF 1-29 twice daily (pre-bed and morning fasted) for body composition. Dose-response plateaus above 300 mcg per injection, so more frequent smaller pulses outperform larger single doses.
Why must it be injected in a fasted state?
Elevated insulin raises somatostatin tone and reduces somatotroph sensitivity, which can blunt the GH pulse by 50-70%. The two reliably fasted windows are pre-bed (2+ hours after the evening meal) and morning on waking before the first meal. Alcohol also suppresses GH and should be avoided within 4 hours of dosing.
How long until results appear?
Effects follow different timelines: improved slow-wave sleep within 1-3 nights, better recovery within 1-2 weeks, measurable IGF-1 elevation (roughly +30-80% with the ipamorelin + MOD-GRF stack) at about 4 weeks, and body-composition changes at 8-12 weeks with consistent dosing. Effects are dose-dependent, so a single daily dose produces subtler changes than a 2-3x daily stacked protocol.
Is ipamorelin safer than injecting growth hormone (somatropin)?
Mechanistically it amplifies the body's own pulsatile GH release via the pituitary, preserving negative feedback and physiologic pulse architecture, whereas somatropin produces tonic, non-pulsatile elevation with a higher burden of insulin resistance and edema. Both share the GH/IGF-1 safety envelope, and active malignancy, diabetic retinopathy, and pituitary tumors are absolute contraindications for either. Ipamorelin is not FDA-approved; somatropin is approved for specific indications.
Is ipamorelin FDA-approved and legal?
It is not FDA-approved for any indication. Clinical development for postoperative ileus reached Phase 2 and was halted, and no active program exists. It is legal to purchase as a research chemical (not for human use) in most jurisdictions, and following the October 2024 PCAC vote it is excluded from 503A compounding. It is also a WADA-prohibited substance for competitive athletes.
Does it affect appetite or cause weight gain?
Mildly. It activates the same GHS-R1a receptor as ghrelin, but its ~2-hour half-life limits tonic activation of hypothalamic feeding neurons, so appetite effects are much smaller than GHRP-6. Scale weight often goes up from increased lean mass and modest fluid retention while fat mass tends to fall, so body-composition tracking is more informative than the scale.
