Ipamorelin

Ipamorelin binds GHS-R1a on somatotrophs and, to a lesser degree, in the hypothalamus, increasing intracellular calcium and provoking GH release while also blunting somatostatin tone. Unlike the earlier GHRPs it shows essentially no activity at ACTH or prolactin release at GH-releasing doses, which is the entire reason it displaced GHRP-2 and GHRP-6 in practice. Because release is pulsatile and the pituitary's releasable GH pool is finite, the GH response plateaus above roughly 200 to 300 mcg in most adults. It synergises strongly with a GHRH analogue, which raises the size of the pulse rather than just its frequency.

Targets: GHS-R1a (ghrelin receptor), Pituitary somatotrophs, Somatostatin tone, IGF-1 axis

• · The single most common real-world protocol. Fasted state matters: circulating glucose and fatty acids blunt the GH pulse.
• · Mimics natural pulsatility more closely. Total daily exposure 300 to 600 mcg. Requires real discipline about food timing.
• · The synergy is genuine and more than additive; this is the classic stack.

Work out your exact syringe units →

• commonHead rush or flushing shortly after injection— Lasts a few minutes and usually fades after the first week.
• commonInjection-site redness or itching— Rotate sites around the abdomen.
• uncommonWater retention and puffiness in hands or face— Dose-dependent and reverses within days of stopping.
• uncommonNumbness or tingling in the hands (carpal tunnel type)— A classic GH-excess sign; drop the dose.
• uncommonIncreased fasting glucose or reduced insulin sensitivity— GH is counter-regulatory to insulin; more likely with prolonged high-dose use.
• uncommonVivid dreams or lighter sleep— Some people get deeper slow-wave sleep, others get the opposite.

• Active or recent malignancy - raising GH and IGF-1 is a poor idea in a proliferative setting.
• Active proliferative diabetic retinopathy.
• Uncontrolled type 2 diabetes, since GH opposes insulin.
• Pregnancy and breastfeeding, where there is no safety data at all.

• synergycjc-1295-no-dac — GHRH plus GHRP produces a larger GH pulse than either alone; this is the standard pairing.
• synergycjc-1295-dac — Widely stacked, though the constant GHRH bleed partially blunts the pulsatile advantage.
• redundantmk-677 — Both act on GHS-R1a. Running them together mostly adds MK-677's appetite and water retention without a proportional GH gain.
• conflictsomatropin — Exogenous GH suppresses the endogenous axis through IGF-1 negative feedback, so a secretagogue has far less to work with.

• · Baseline and 8-to-12-week IGF-1, aiming to sit in the upper half of the age-adjusted reference range rather than above it.
• · Fasting glucose and HbA1c if running longer than 12 weeks.
• · Track morning fasted weight and ring or shoe tightness as a crude fluid-retention signal.

Not approved as a drug anywhere. It was removed from the US compounding-permitted bulk substances category by the FDA in 2023 and is sold as a research chemical; it is also a prohibited substance in sport under WADA S2.

• Raun et al. 1998, Ipamorelin, the first selective growth hormone secretagogue (preclinical)
• Helsinn phase 2 programme of ipamorelin for postoperative ileus, which failed its primary endpoint (trial)
• WADA Prohibited List, section S2 growth hormone secretagogues (guideline)

GHS-R1a is a Gq-coupled receptor with unusually high constitutive activity - roughly half its maximal signalling occurs with no ligand bound at all. Ipamorelin binding drives phospholipase C, which cleaves PIP2 into IP3 and DAG; IP3 releases calcium from intracellular stores while DAG activates protein kinase C, and the resulting calcium spike triggers exocytosis of pre-formed GH granules. That is the whole reason the response is a discrete pulse rather than a plateau: it empties a granule pool that then has to be refilled, and it is also why dose-response flattens above roughly 200 to 300 mcg. The granule pool, not the receptor, is the limiting factor. Selectivity is the other half of the story. GHRP-6 and hexarelin recruit arginine vasopressin release and thereby drive the HPA axis, which is how they raise ACTH and cortisol; ipamorelin's Aib-His N-terminus does not, and Raun's original work showed no ACTH or cortisol response at doses over 200 times the GH-releasing ED50. Its hypothalamic action - suppressing somatostatin tone in the periventricular nucleus - does not require crossing an intact blood-brain barrier, because the arcuate nucleus and median eminence sit outside it. That is worth understanding, because it means the CNS effects are real without the molecule ever being brain-penetrant in the usual sense.

The most common failure is food. Circulating glucose and free fatty acids blunt somatotroph responsiveness, so injecting 45 minutes after dinner gets you a fraction of the pulse you paid for - two hours fasted before, and thirty minutes after, is not fussiness, it is the difference between working and not. The second failure is dose inflation: people who feel nothing at 300 mcg go to 500 or 1000 mcg, which does almost nothing for GH because the releasable granule pool is already empty, and instead buys water retention and a bigger bill. Third is product identity. Ipamorelin has no distinctive subjective signature beyond a brief head rush, so a completely inert or mislabelled vial feels identical to a good one, and the only way to know is an IGF-1 draw. If you develop hunger, prolactin symptoms or a cortisol-like flat feeling on ipamorelin, the reasonable first hypothesis is that you have GHRP-2 or GHRP-6 in the vial. Finally, carpal tunnel symptoms - numb or tingling hands on waking - are the earliest reliable sign of too much GH signalling and should be treated as a dose instruction rather than an inconvenience.

• GHS-R1a (ghrelin receptor), pituitary somatotroph — Low nanomolar in binding assays; the human pharmacodynamic EC50 for GH release was 214 nmol/L plasma concentration in Gobburu et al. 1999

  Gq/PLC activation, IP3-driven calcium release, exocytosis of stored GH granules. A single episodic GH surge peaking around 40 minutes after the end of an intravenous infusion.

• GHS-R1a, hypothalamic arcuate and periventricular nuclei — Not separately quantified in humans

  Reduces somatostatin output, removing the brake on the somatotroph. This is the component that makes a GHRH analogue work far better when co-administered.

• ACTH / cortisol axis — No measurable activity at GH-releasing doses

  Explicitly absent. This is the defining property of the molecule and the entire reason it displaced GHRP-2 and GHRP-6.

• Arcuate NPY/AgRP appetite circuitry — Not characterised in humans

  Clinically minimal. Users report little to no appetite change, in sharp contrast to GHRP-6 and MK-677.

• Ipamorelin 201 Study Group, proof-of-concept trial for postoperative ileus after bowel resection 2 · 2014

  Time to first tolerated meal. Median 25.3 hours on ipamorelin versus 32.6 hours on placebo, p = 0.15 - numerically favourable, statistically negative. Ipamorelin was well tolerated. This is the only randomised controlled trial of ipamorelin in humans and it did not meet its endpoint.

• Gobburu et al., single-dose ascending intravenous pharmacokinetic and pharmacodynamic study in healthy male volunteers 1 · 1999

  Dose-proportional kinetics with terminal half-life 2 hours, clearance 0.078 L/h/kg, steady-state volume of distribution 0.22 L/kg. A single episodic GH surge peaking around 40 minutes, with EC50 of 214 nmol/L. This is where essentially every real number about ipamorelin comes from.

GH begins rising within 15 minutes and peaks around 30 to 40 minutes after a subcutaneous dose, back to baseline inside two to three hours. Subjectively, deeper or more vivid sleep is usually the first thing people notice, typically within the first week. Recovery between training sessions and reduced joint soreness show up around weeks two to four. IGF-1 has usually moved measurably by week four and is at its new plateau by week eight. Body composition changes, where they happen at all, are a twelve-week-plus phenomenon and are small compared with what exogenous GH does.

The pairing that actually earns its place is a GHRH analogue - Mod GRF 1-29 at 100 mcg, or sermorelin, drawn into the same syringe. The two act on different receptors and the combined pulse is larger than the arithmetic sum, because ipamorelin removes the somatostatin brake while the GHRH arm determines how hard the accelerator is pressed. Stacking ipamorelin with MK-677, GHRP-2, GHRP-6 or hexarelin is pointless: they all compete for GHS-R1a, so you get one receptor's worth of effect plus the other compound's side effects. Ipamorelin plus BPC-157 or TB-500 is extremely common in recovery stacks and there is no pharmacological conflict, but there is also no combination data - you are running two independent bets, not a synergy. The genuinely important negative is exogenous GH: once somatropin is on board, IGF-1 feedback shuts down the pituitary and there is nothing left for a secretagogue to release. Running both is paying for one.

Against GHRP-2: ipamorelin gives a smaller GH pulse but essentially no prolactin or cortisol drift, and no meaningful hunger. If you want maximum acute GH and can tolerate prolactin creep, GHRP-2 wins; for anything run longer than a few weeks, ipamorelin is the better trade. Against hexarelin: hexarelin produces the largest pulse of any of them and desensitises within about two weeks, whereas ipamorelin can be run for months. Against GHRP-6: GHRP-6's hunger is a feature only if you are trying to gain weight and cannot eat. Against MK-677: MK-677 hits the same receptor orally and raises IGF-1 far more, but with real glucose deterioration, persistent appetite and water retention - ipamorelin is the low-side-effect, low-effect-size option and MK-677 is the opposite. Against exogenous somatropin: not comparable. Somatropin bypasses every regulatory ceiling and produces IGF-1 elevations a secretagogue cannot approach, along with the side-effect profile to match.

$35–$90/month. Approximate grey-market research-chemical pricing. A 5 mg vial typically runs 25 to 50 USD; at 250 mcg nightly you use about 7.5 mg per month, so roughly one and a half vials. Compounded pharmacy ipamorelin, where still obtainable, is several times that. These are observed street prices, not quoted from any vendor list, and they move.

• ?No published subcutaneous bioavailability, tmax or absolute exposure figure exists. The half-life, clearance and volume of distribution quoted everywhere come from an intravenous study.
• ?The sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 is consistent with the confirmed molecular formula C38H49N9O5 and molecular weight 711.9 (PubChem CID 9831659), but the residue-by-residue sequence was not independently resolved in this session, so it is flagged unverified.
• ?GHS-R1a binding affinity for ipamorelin is widely quoted in the low nanomolar range but the primary source for a specific Ki value was not resolved here.
• ?Whether ipamorelin crosses an intact blood-brain barrier is genuinely unknown. Its hypothalamic effects do not require it to, because the relevant nuclei are adjacent to circumventricular organs.
• ?There is no human data at all on chronic dosing beyond a few weeks, on receptor desensitisation timelines, or on body composition. The 12-week-on, 4-week-off convention is folklore with a plausible mechanism behind it, not a studied schedule.
• ?The claim that ipamorelin is superior to other GHRPs for sleep architecture specifically is not supported by any polysomnography study that this session could locate.

• Ipamorelin, the first selective growth hormone secretagogue Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH, European Journal of Endocrinology, 1998 · PMID 9849822

  The founding paper. Establishes that ipamorelin releases GH with a selectivity comparable to GHRH itself, and specifically that it does not raise ACTH or cortisol at doses more than 200-fold above its GH-releasing dose.

• Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers Gobburu JV, Agersø H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999 · PMID 10496658

  The source of every genuine human PK number for ipamorelin: half-life 2 hours, clearance 0.078 L/h/kg, Vss 0.22 L/kg, EC50 214 nmol/L, GH peak at roughly 40 minutes.

• Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014 · PMID 25331030

  The only randomised controlled human trial of ipamorelin. Negative on its primary endpoint but reassuring on tolerability.