Selective growth hormone secretagogue receptor (GHSR-1a / ghrelin) agonist; pentapeptide ghrelin mimetic

Ipamorelin

CAS: 170851-70-4 MW: 711.85 g/mol Formula C38H49N9O5

Key takeaways

  • The community indication (body composition / recovery / sleep) has never been tested in humans at any dose. The only human Phase 2 trial — Beck 2014 / NCT00672074 for postoperative ileus, n=114 — missed its primary endpoint, and development was formally discontinued. Two fatal SAEs occurred in the ipamorelin arm (causal attribution not established, imbalance flagged by FDA). ⚠️
  • The clinic / community standard dose (100–300 mcg sub-Q) is approximately 10× lower than the dose used in the only published human PK/PD study (Gobburu 1999: ~0.03 mg/kg IV ≈ 2.4 mg in an 80 kg adult). Community "no IGF-1 movement on bloodwork" complaints are the predictable consequence of this dose disconnect, not necessarily evidence the molecule is inactive.
  • The foundational selectivity claim — that ipamorelin releases GH without cortisol, ACTH, or prolactin elevation — derives entirely from a single Novo Nordisk research group (Raun 1998) 🔴 and has never been independently replicated in humans. Long-term and supratherapeutic chronic-dose human selectivity remains uncharacterised.
  • On 29 October 2024 the FDA Pharmacy Compounding Advisory Committee voted 0–12–1 against placing ipamorelin (free base) and ipamorelin acetate on the §503A bulks list. As of 14 May 2026, ipamorelin remains outside the legal US compounding pathway. Australia's TGA classifies ipamorelin as Schedule 4 with Appendix D possession restriction (since February 2016). WADA 2026 Prohibited List S2.2.4 names it explicitly.
  • Community Score A/80 reflects ~18 years of continuous forum presence (since the 2008–2012 DatBtrue era), high stack centrality (the dominant companion peptide in the CJC-1295 + ipamorelin combo that defined US telehealth peptide prescribing 2018–2024), and tight protocol codification — but lower effect-consistency than other A-tier peptides due to the IGF-1 dispute, the Huberman-vs-MPMD disagreement on hunger, and the "I lost more weight in my wallet than in body fat" outcome frequency in long logs.

1. Identity

FieldValueSource
INN / common nameIpamorelin (no marketed INN-bearing product)[Academic secondary source — DrugBank DB12370]
Research codesNNC 26-0161 (Novo Nordisk discovery designation); historically conflated with NN703 / NNC-26-0703 (related but distinct analogs)[Peer-reviewed — Raun 1998, PMID 9849822] 🔴
CAS (free base)170851-70-4[Regulatory — FDA PCAC Briefing Document, Oct 2024]
CAS (acetate salt)1258196-85-8 (commonly mis-cited as 170851-70-4 in vendor literature)[Regulatory — FDA PCAC Briefing Document, Oct 2024]
UNII (free base)Y9M3S784Z6[Regulatory — FDA PCAC Briefing Document, Oct 2024]
Molecular formulaC₃₈H₄₉N₉O₅[Regulatory — FDA PCAC Briefing Document, Oct 2024]
Molecular weight711.85 g/mol (free base)[Regulatory — FDA PCAC Briefing Document, Oct 2024]
SequenceH-Aib-His-D-2-Nal-D-Phe-Lys-NH₂ (C-terminal amide; pentapeptide with non-proteinogenic Aib and D-2-Nal)[Peer-reviewed — Raun 1998, PMID 9849822]
ClassSelective growth hormone secretagogue receptor 1a (GHSR-1a / ghrelin receptor) agonist; ghrelin mimetic; pentapeptide GHS[Peer-reviewed — Raun 1998, PMID 9849822]
Brand namesNone — no approved human medicinal product anywhere globally[Regulatory — FDA PCAC Briefing Document, Oct 2024]
Terminal half-life (IV, healthy men)≈ 2 hours (two-compartment; CL ≈ 0.078 L/h/kg; Vss ≈ 0.22 L/kg)[Peer-reviewed — Gobburu 1999, PMID 10496658] ⚠️
IUPHAR/BPS GtoPdbListed within GHSR / ghrelin receptor agonist class[Academic secondary source — IUPHAR/BPS Guide to Pharmacology]
PubChem CID9831659[Academic secondary source — PubChem CID 9831659]
DrugBank IDDB12370 (investigational)[Academic secondary source — DrugBank DB12370]

2. History and Development

Ipamorelin was discovered by a Novo Nordisk medicinal-chemistry programme in the mid-1990s as one of a series of pentapeptides derived by truncation of the central Ala-Trp dipeptide of GHRP-1. The lead publication is Raun et al., European Journal of Endocrinology 1998 [Peer-reviewed — PMID 9849822] ⚠️ 🔴. The composition-of-matter patent is EP 0736039 B1. Internal Novo Nordisk designation: NNC 26-0161; the codes NN703 / NNC-26-0703 frequently used in lay literature refer to related analogs and should not be treated as synonyms.

After early human pharmacokinetic / pharmacodynamic characterisation in 48 healthy male volunteers [Peer-reviewed — Gobburu 1999, PMID 10496658] ⚠️, Novo Nordisk did not advance ipamorelin to a registrational programme for growth-hormone deficiency, and rights passed to Helsinn Healthcare (Lugano, Switzerland), which pursued the molecule as a ghrelin-receptor agonist for postoperative ileus (POI) through Helsinn Therapeutics (U.S.), Inc.

The pivotal Phase 2 POI trial (NCT00672074, “Ipamorelin 201 Study”) completed enrolment of 114 evaluable patients and was published in 2014 [Peer-reviewed — Beck 2014, PMID 25331030] ⚠️. It did not show a statistically significant benefit on the primary efficacy endpoint (time to tolerance of a standardised solid meal: 25.3 h vs 32.6 h placebo, P > 0.05). A subsequent narrative review stated explicitly that “due to these disappointing results, [ipamorelin’s] development was discontinued” [Peer-reviewed secondary — Ishida 2020, as cited in FDA PCAC Briefing Document].

There is no record in Drugs@FDA, the EMA EPAR database, MHRA, TGA ARTG, Health Canada DPD, PMDA, NMPA, MFDS, or GRLS of any approval, conditional approval, or active IND for ipamorelin for any indication as of 2026-05-16. The molecule remains investigational worldwide. The most recent peer-reviewed work using ipamorelin (Lu et al. 2024, Helsinn-affiliated authors; PMID 39043357) is a ferret model of cisplatin-induced anorexia comparing ipamorelin to anamorelin — preclinical and explicitly not a re-initiation of human development.

3. Mechanism of Action

3.1 Demonstrated in humans

  • Selective GH release via GHSR-1a agonism. Single intravenous doses of 14.04–140.45 nmol/kg in healthy men produced concentration-dependent, episodic plasma GH peaks (maximum ≈ 465 mIU/L at ≈ 40 min post-dose), declining to baseline by 6 h [Peer-reviewed — Gobburu 1999, PMID 10496658] ⚠️ 🔴.
  • Linear pharmacokinetics. Two-compartment behaviour; t½ ≈ 2 h; CL ≈ 0.078 L/h/kg; Vss ≈ 0.22 L/kg [Peer-reviewed — Gobburu 1999].
  • Selectivity claim in humans. The published human selectivity profile (no clinically meaningful rises in prolactin, ACTH, cortisol, aldosterone, FSH, LH, TSH) derives from a small healthy-volunteer cohort with the Novo Nordisk swine selectivity dataset as the foundational comparator. Single-group origin [Peer-reviewed — Raun 1998] 🔴 ⚠️.

3.2 Proposed / preclinical only

  • Hypothalamic + pituitary site of action. GHSR-1a receptors are densely expressed on hypothalamic GHRH neurons and on anterior-pituitary somatotrophs. Ipamorelin’s GH-releasing potency in primary rat pituitary cultures EC₅₀ ≈ 1.3 nM; in vivo ED₅₀ ≈ 80 nmol/kg in pentobarbital-anaesthetised rats [Peer-reviewed preclinical — Raun 1998] 🔴.
  • Selectivity vs GHRP-2 / GHRP-6 / hexarelin. In swine, GHRP-6 and GHRP-2 produced concurrent ACTH and cortisol elevation; ipamorelin did not, at doses ≥ 200× its ED₅₀ for GH release [Peer-reviewed preclinical — Raun 1998] 🔴. This single-group finding is the foundational basis of community preference for ipamorelin over older GHRPs.
  • GI prokinetic activity. In rodent and ferret models, ipamorelin accelerates gastric emptying and colonic transit via cholinergic-vagal ghrelin-receptor-mediated mechanisms [Peer-reviewed preclinical — Venkova 2009; Pietra 2011; Lu 2024 PMID 39043357] ⚠️.
  • Reward / addiction potential (class). Ghrelin-receptor activation in the ventral tegmental area modulates dopamine release and drug-seeking in rodents. Ipamorelin’s reinforcement potential has not been directly characterised but is identified by the FDA as a class-level theoretical concern [Regulatory — FDA PCAC Briefing Document, Oct 2024].
  • Reproductive toxicity (class). Both ghrelin-receptor activation and antagonism in mice negatively affected fertilisation, implantation, and embryo-fetal development (Luque 2014); whether ipamorelin shares this class effect is unconfirmed [Regulatory — FDA PCAC Briefing Document, Oct 2024].

4. Regulatory Status

4.1 Drug-regulatory status

AuthorityStatus (2026-05-16)
US FDANot approved for any indication. No active IND. Was studied under Helsinn IND for POI ca. 2008–2014 (NCT00601679 terminated; NCT00672074 Phase 2 negative). §503A: placed in Category 2 on 29 September 2023; removed 27 September 2024 after nominators withdrew. PCAC vote 29 October 2024: 0 Yes / 12 No / 1 Abstain against placing both free base and acetate on the 503A bulks list, citing inadequate characterisation, immunogenicity concerns, and absence of supporting safety/efficacy data. As of 14 May 2026, ipamorelin does not appear on the Category 1 list or the final 503A bulks list and remains ineligible for legal compounding under §503A. No final notice-and-comment rulemaking has been published. §503B: acetate placed in Category 2 of interim 503B list; no Category 1 listing. Last reported outsourcing-facility compounding ≈ 2020. [Regulatory — FDA PCAC Final Summary Minutes 29 Oct 2024; FDA 503A Bulk Drug Substances List 2026-05-14]
EMANever approved; no EPAR; no orphan designation.
MHRA (UK)Not listed; not authorised.
TGA (Australia)Not in ARTG. February 2016 ACMS recommended, and the delegate confirmed, adding ipamorelin to the Poisons Standard as a Performance and Image Enhancing Drug; Schedule 4 (Prescription Only) with Appendix D possession restriction. No subsequent reclassification in the Therapeutic Goods (Poisons Standard — October 2025) Instrument 2025. [Regulatory — TGA Poisons Standard October 2025]
Health CanadaNot in DPD; no Notice of Compliance.
PMDA (Japan)Not approved; no public regulatory action.
NMPA (China)Not approved.
MFDS (Korea)Not approved.
GRLS (Russia)Not on the state register.
WHO EMLNot listed.

4.2 Anti-doping status

  • WADA 2026 Prohibited List (in force 1 January 2026): ipamorelin is prohibited at all times (in- and out-of-competition) under S2.2.4 “Growth Hormone Releasing Factors” — specifically the “growth hormone secretagogues (GHS) and their mimetics” sub-bullet, explicitly named alongside anamorelin, capromorelin, ibutamoren (MK-677), lenomorelin (ghrelin), macimorelin, and tabimorelin [Anti-doping — WADA 2026 Prohibited List, S2.2.4]. (Note: the FDA PCAC briefing document cites “S2.4” reflecting the older 2022/2023 list numbering; current 2026 placement is S2.2.4.)
  • TUE eligibility: in principle available under the standard process; in practice not granted, because ipamorelin is not an approved medicine and no recognised therapeutic indication exists.
  • NCAA banned-drug classes: captured under “Peptide hormones, growth factors, related substances and mimetics.”
  • DoD/OPSS: flagged as a prohibited/high-risk peptide ingredient; named in OPSS “ingredients to avoid” guidance.
  • Global DRO (UK/USA/Canada/Japan/Australia, checked 2026-05-16): ipamorelin returns as Prohibited at all times in all jurisdictions [Anti-doping — Global DRO, queried 2026-05-16].
  • BSCG advisories: ipamorelin identified as a contaminant of concern in the unregulated “research peptide” supply chain.
  • Detection. Ipamorelin and related GHS have been detected in athlete-confiscated vials in Germany, Belgium, Australia, and the USA [Cox et al. 2015, as cited in FDA PCAC Briefing Document]. WADA-accredited labs use targeted LC-MS/MS optimised for short-chain peptides. Typical urine detection window after sub-Q administration is short (hours); plasma/serum and dried-blood-spot methods extend it.
  • Named athlete sanctions involving ipamorelin specifically: none located on this pass; cases involving GHS more broadly typically name GHRP-2 or GHRP-6.

4.3 Last regulatory review

Last regulatory review: 2026-05-16

5. Formulations and Routes

  • Investigational dosage forms in published trials: intravenous infusion (0.03 mg/kg twice daily over 7 days for POI; 4.21–140.45 nmol/kg single 15-minute IV infusion in the PK/PD study) [Peer-reviewed — Beck 2014; Gobburu 1999] ⚠️.
  • No approved formulation exists anywhere.
  • Compounding-pharmacy products in the US (historical, now restricted): prepared by 503A pharmacies as lyophilised powder for subcutaneous injection at concentrations including 0.6 mg/mL, 1.5 mg/mL, and proposed 2 mg/mL (the latter exceeds the reported aqueous solubility of the free base, 0.0032 mg/mL — FDA flagged as a formulation feasibility concern). Also reported in sublingual troches and rapid-dissolve tablets despite no published bioavailability data for non-injectable routes. Following the September 2023 Category 2 placement, outsourcing-facility reports declined to zero by H2 2020; the October 2024 PCAC vote means ipamorelin remains outside the legal §503A pathway [Regulatory — FDA PCAC Briefing Document Oct 2024; FDA 503A Bulks List 2026-05-14].
  • Storage. Lyophilised free base stable ~3 weeks at room temperature; long-term storage desiccated below −18 °C; solution stability ~2–3 weeks at 4 °C.

6. Preclinical Evidence

All foundational ipamorelin pharmacology data derive from the Novo Nordisk group (Raun, Hansen, Johansen, Ankersen, Madsen, Andersen; Måløv, Denmark), creating a 🔴 single-group dependency that has been only partially mitigated in subsequent decades.

  • GH-releasing potency in primary rat pituitary cells: EC₅₀ ≈ 1.3 nM; efficacy ≈ 85% of GHRP-6 maximum [Peer-reviewed preclinical — Raun 1998, PMID 9849822] ⚠️ 🔴.
  • In vivo GH release: ED₅₀ ≈ 80 nmol/kg in anaesthetised rats; ≈ 2.3 nmol/kg in conscious swine [Peer-reviewed preclinical — Raun 1998] 🔴.
  • Selectivity vs cortisol/ACTH/PRL: ipamorelin did not raise ACTH or cortisol at doses > 200× its ED₅₀ in swine; GHRP-2 and GHRP-6 did [Peer-reviewed preclinical — Raun 1998] 🔴.
  • POI rodent models (Helsinn-funded): ipamorelin 0.014–1.0 µmol/kg IV accelerated gastric emptying and colonic transit; effects reversed by ghrelin antagonism [Peer-reviewed preclinical — Venkova 2009; Pietra 2011] ⚠️.
  • Cisplatin-induced weight loss in ferrets (Helsinn-affiliated authors): ipamorelin 1–3 mg/kg IP reduced cisplatin-induced weight loss by ≈ 24% during the 48–72 h delayed phase; no antiemetic effect after IP administration [Peer-reviewed preclinical — Lu 2024, PMID 39043357] ⚠️.
  • Tilapia HPG-axis model: chronic ipamorelin acetate increased LH, 11-ketotestosterone, androgen-receptor expression, and spermatogenesis in Oreochromis mossambicus — a class-level ghrelin effect on the reproductive axis, mechanistically interesting but with no direct human translational claim [Peer-reviewed preclinical — Gouda 2024, PMID 38996787].

Cochrane has not produced a preclinical synthesis.

7. Clinical Evidence

7.1 Cochrane / systematic reviews

A Cochrane Database search (performed by FDA in the October 2024 PCAC briefing and independently for this refresh) identified no Cochrane systematic review specific to ipamorelin for any indication as of 2026-05-16 [Cochrane Library, queried 2026-05-16 — no matching record]. Adjacent Cochrane work on POI focuses on alvimopan and gum chewing.

7.2 Phase 1 / PK-PD

Gobburu 1999 [Peer-reviewed — PMID 10496658] ⚠️ 🔴. Randomised, placebo-controlled, dose-escalation single-IV-infusion study in 48 healthy men (5 active dose groups of 6 + 2 placebo each at 4.21, 14.04, 42.13, 84.27, 140.45 nmol/kg). Established linear PK (t½ ≈ 2 h) and a linear concentration–GH-release relationship with peak GH ≈ 465 mIU/L. No adverse events specifically attributed to ipamorelin. Funded by Novo Nordisk; single-group origin of dataset.

This is the only published human PK/PD study of ipamorelin. The dose range translates to ~340 mcg to ~11 mg in an 80 kg adult — note the relationship to community-channel doses (typically 100–300 mcg sub-Q, an order of magnitude below the lowest IV trial dose).

7.3 Phase 2

Beck 2014 / NCT00672074 (Ipamorelin 201 Study) [Peer-reviewed — PMID 25331030] ⚠️. Multicentre, double-blind, placebo-controlled Phase 2 in 117 adults undergoing small/large bowel resection (114 in mITT). Intervention: ipamorelin 0.03 mg/kg IV twice daily for up to 7 days. Primary endpoint (time from first dose to tolerance of a standardised solid meal) not met: 25.3 h vs 32.6 h placebo (P > 0.05). No statistically significant differences for secondary endpoints (GI-2, time to first flatus, length of stay, readiness for discharge). Subgroup signal in open-laparotomy patients only. Funded by Helsinn Therapeutics. Authors concluded the drug was well tolerated but did not improve primary efficacy.

  • NCT00601679 — Helsinn-sponsored POI study sometimes cited in older trial lists. Listed on ClinicalTrials.gov as terminated/withdrawn; results not posted; no peer-reviewed publication.
  • NCT01280344 — additional ipamorelin study in bowel-resection patients referenced in the FDA M-CERSI report; no peer-reviewed publication.

7.4 2024–2026 trial sweep

No new ipamorelin-specific interventional trials registered between January 2024 and 16 May 2026 in ClinicalTrials.gov or the EU Clinical Trials Information System with ipamorelin as an investigational agent. 2024–2026 PubMed literature is exclusively reviews and preclinical (Lu 2024 ferret; Gouda 2024 fish; Mayfield 2026, Rahman 2026, Coutinho 2026, Mavrych 2026, Renke 2026, Mendias 2026 — all narrative reviews).

7.5 Disputed Claims

Status as of 2026-05-16: No substantive published peer-reviewed scientific dispute identified. Three potential controversies were examined and characterised as data gaps rather than active disputes:

  1. Selectivity claim (no cortisol/ACTH/prolactin rise). Foundational data trace to a single Novo Nordisk swine experiment and a small healthy-volunteer dataset. No peer-reviewed paper contradicts the selectivity claim with human data at supratherapeutic chronic dosing — but no independent group has replicated it in humans either. This is a 🔴 single-group dependency, not a dispute. Mendias & Awan 2026 (Sports Med, PMID 41966639) and Coutinho et al. 2026 (J Sports Med Phys Fitness, PMID 41880199) both note that selectivity has been demonstrated only under short-term controlled dosing and may not extrapolate to the supraphysiological combined protocols typical in non-medical use.
  2. GH-pulse amplitude vs total integrated exposure. The Gobburu 1999 PK/PD model itself noted that “prolonged exposure to the peptide may not necessarily produce GH stimulation for long periods” — i.e., tachyphylaxis at the somatotroph level. The FDA echoed this framing in its October 2024 briefing document as a clinical concern rather than a dispute.
  3. IGF-1 response. No peer-reviewed controlled chronic-dosing IGF-1 dataset exists for ipamorelin in humans. The “sustained IGF-1 elevation” claim widely circulated outside peer-reviewed literature is addressed in §7B (community layer) and is not adopted here.

No retractions of cited ipamorelin papers were identified.

7B. Community Evidence Layer

The community-evidence layer (Pass 2, 2026-05-16) is summarised here. Full sourcing in ipamorelin_com_2026-05-16_A80.md. Community Score 80 / 100, Community Tier A.

7B.1 Adoption timeline

  • 2005–2010. Earliest sustained discussion in bodybuilding forums (EliteFitness, AnabolicMinds, ProfessionalMuscle, MESO-Rx) follows the “DatBtrue tradition” — an anonymous figure who systematised the saturation-dose framework (100 mcg or 1 mcg/kg of a GHRP paired with Modified GRF (1-29)). In that tradition ipamorelin was positioned as the “cleaner but weaker” GHRP — discussed but second-tier to GHRP-2/6 because the GH pulse was lower.
  • 2012–2018. Migration from pure bodybuilding boards into the men’s-health / TRT-clinic conversation through ExcelMale, Defy Medical, Tier 1 Health Club, Cenegenics. Ipamorelin’s selectivity (no cortisol/prolactin spike vs GHRP-6) became its defining selling point.
  • 2018–2023. Compounding pharmacies (Empower, Tailor Made, Hallandale, Olympia, Strive, Wells, Pure) routinely shipped CJC-1295 / ipamorelin combo vials to physician-supervised telehealth patients. Jay Campbell’s books and Ben Greenfield’s “Wolverine Peptide Stack” institutionalised the 200 mcg sub-Q daily, 5-on/2-off, 8-on/8-off template.
  • April 2024. Huberman Lab “Benefits & Risks of Peptide Therapeutics” episode names ipamorelin in the Type-2 GH-secretagogue section. Huberman frames ipamorelin as “increases ghrelin which increases hunger but does increase GH release and improves deep sleep (though maybe at the expense of REM)” — a framing that confused the community because the academic literature has long held ipamorelin as the least hunger-stimulating GHRP. Search-volume and clinic-intake inquiries spiked.
  • 29 October 2024. FDA PCAC voted against placing ipamorelin acetate on the 503A bulks list. Compounding pharmacies with ipamorelin in formulary discontinued or significantly restricted programmes through Q4 2024 / Q1 2025, producing sharp grey-market migration.
  • October 2024 onward. Huberman Lab #156 (Dr. Craig Koniver, 7 Oct 2024) reintroduced ipamorelin as part of a multi-peptide bedtime stack (BPC-157 + ipamorelin + tesamorelin) at 100 mcg. By Q2 2026, with three peptides (CJC-1295, ipamorelin, thymosin α-1) reportedly re-categorized for prescription access per Huberman’s pre-recording update, ipamorelin is again being marketed by telehealth platforms but at narrower formularies and higher per-script prices than the 2022–2024 peak.

7B.2 Documented protocols (representative sources, dose range)

The dominant community protocol is 100–300 mcg per injection, 1–3× daily sub-Q, almost always paired with CJC-1295 (no-DAC), cycled 5 days on / 2 off and 8 weeks on / 8 weeks off. Reconstitution math standardised across vendors: 3.0 mL bac water into 10 mg/10 mg CJC-no-DAC + ipa blend → ~33 mcg of each peptide per U-100 insulin unit. Representative sources: DatBtrue Austeroids archive (100 mcg or 1 mcg/kg, 3×/day); Ben Greenfield Wolverine Peptide Stack (200 mcg ipa + 200 mcg CJC no-DAC pre-bed, 5-on/2-off, 8–10 weeks on/off); Jay Campbell (200 mcg + 200 mcg AM, 5-on/2-off, 8/8); Huberman Lab #156 / Koniver (100 mcg bedtime in BPC + ipa + tesa stack); PeptideDeck / PeptideDosages (200–300 mcg per injection); Perfect B clinic (0.6 mg week 1 escalating to 2.0 mg by month 2, CJC + ipa combined).

A meaningful minority of clinic-prescribed protocols use 350–500 mcg per injection for low-IGF-1 patients (ExcelMale “Ipamorelin Dosage Discussion” thread; clinic-prescribed 350 mcg pre-bed). The ExcelMale “Ipamorelin and IGF-1” thread is the canonical place where forum SME “BigTex” argues that “500 mcg of ipamorelin is the starting point if you want to see your GH and IGF-1 levels rise” — a community-side acknowledgement that the standard 100–300 mcg dose may not move IGF-1 measurably.

7B.3 Claimed effects (frequency-tagged)

  • Improved sleep depth, more vivid dreams — widespread. Often the first reported effect, within days. ExcelMale, Greenfield, Campbell, Koniver, virtually every long-form log.
  • No cortisol / prolactin spike (the “selectivity” claim) — widespread, treated as ipamorelin’s defining property. Derek MPMD substack: “the cleanest GHRP… the precision tool.”
  • Minimal hunger spike vs GHRP-6/2 — “cutter-friendly” — widespread, with notable dissent. Huberman’s April 2024 episode is the prominent dissent (framing ipa as ghrelin-mediated hunger-inducer); most named sources disagree.
  • Recovery / reduced soreness — common.
  • Subcutaneous fat loss / midsection tightening — common, contested in magnitude. Koniver (Huberman #156): “subcutaneous fat reduction from the ipamorelin, visceral fat reduction from the tesamorelin.” Counterclaim users describe results as “very subtle, requires tight diet.”
  • Lean mass preservation / mild recomp in stack context — common. Increasingly framed as the “Ozempic butt” mitigation add-on to GLP-1 therapy (California Trim Clinic Feb 2026; Advanced Scripts Pharmacy “Peptide Stacking 101”).
  • Skin quality and “glow” — common. Koniver: “their skin would be better… more durable.”
  • IGF-1 elevation on bloodwork — disputed/inconsistent. Multiple users on ExcelMale at 100–200 mcg report no IGF-1 movement; community SMEs suggest 500 mcg threshold to see lab-detectable change. Directly maps to the dose-disconnect gap analysis in §11B.
  • Joint comfort — occasional; community redirects to BPC-157 / TB-500.
  • “Wasted my money” / nothing-felt outcome — occasional, surfaces in most multi-month logs. Representative ExcelMale post: “I’ve lost more weight in my wallet than bodyweight.”

7B.4 Reported side effects

Injection-site reactions (mild, transient — common); headache / head pressure first 1–2 weeks (common, GH-mediated intracranial pressure attribution); lethargy / daytime fatigue early use (common, mitigated by bedtime-only dosing); water retention / mild bloat (occasional with monotherapy, more common with CJC + DAC pairings); numbness / tingling in hands and feet (occasional, more in CJC + DAC discussions); blood glucose elevation (occasional, mild at community doses; flagged as risk for diabetics); increased appetite (disputed — Huberman vs. dominant community framing); tachyphylaxis / desensitisation on chronic high-dose use (occasional, addressed by 8-on/8-off cycling); no IGF-1 movement on bloodwork (functions as an “absence-of-effect” complaint, frequency-common).

7B.5 Community dissent

Four real community disagreements, surfaced rather than smoothed:

  1. Does ipamorelin actually move IGF-1 at community-typical sub-Q doses? The ExcelMale “Ipamorelin and IGF-1” thread is the canonical place this dispute lives. Three positions in the same thread: GH pulse is real even if IGF-1 doesn’t track; if IGF-1 doesn’t move, product is junk; you have to dose at ≥500 mcg to see lab movement. This is the community-side acknowledgement of the dose-disconnect that §11B subclass #4 codifies.
  2. The “ipamorelin is weak / why not GHRP-2 or tesamorelin” school. AnabolicMinds dating to the DatBtrue era: “slightly weaker than GHRP-6.” Derek MPMD ranks ipamorelin at low-to-moderate GHRP strength. The Peptide Catalog frames it as “tesa + ipa is the strongest body-comp stack; CJC + ipa is the cheaper, widely available starter stack… not weak, but smaller in magnitude.”
  3. “Failed POI Phase 2 means the molecule is weak.” Skeptical minority post-2024 PCAC vote — Substack “The Evidence Gap”: “Zero published human composition RCTs of ipamorelin monotherapy. Phase 2b POI program (Helsinn) explored bowel-motility recovery, not body composition. The compound entered the research chemical market and has lived there ever since.”
  4. The 2024 PCAC vote — community response. Three camps: compounding-pharmacy clinicians treating the vote as a regulatory disaster pushing patients toward less-regulated grey-market sources; research-peptide vendors absorbing displaced demand; skeptical biohacker minority accepting the PCAC decision as appropriate given thin clinical evidence (Substack “Evidence Gap” tradition; Bolt Pharmacy UK guide).

7B.6 Stack patterns

Ipamorelin is almost never run as monotherapy. Ranked by documented frequency:

  • CJC-1295 no-DAC + ipamorelin — by far the dominant pairing; canonical “GHRH + GHRP synergy” stack; premixed 10 mg / 10 mg blend vials are the dominant SKU.
  • CJC-1295 with DAC + ipamorelin — minority pairing with active community pushback (Greenfield explicitly warns against; Campbell and Koniver prefer no-DAC). DAC’s 5–8 day half-life “fights” ipa’s 1.5–2.5 h pulse, mismatching pulsatile physiology. Side-effect reports (water retention, tingling) cluster more with the DAC pairing.
  • Sermorelin + ipamorelin — secondary pairing, dispensed by compounding pharmacies. ExcelMale moderator consensus tends to view sermorelin as “not very effective due to very short half life” and prefer CJC no-DAC.
  • Tesamorelin + ipamorelin — clinically-strongest GHRH-side pairing per community summaries. Koniver describes a BPC + tesa + ipa bedtime tri-stack. Considered the “premium recomp” stack at meaningfully higher cost.
  • Ipamorelin + MK-677 — uncommon; community considers redundant (both hit GHSR-1a).
  • Ipamorelin stacked into TRT cycles — common (175 mg/wk Test Prop + ipa/CJC for recovery and recomp; some add IGF-1 LR3 during cutting blocks).
  • Ipamorelin during GLP-1 weight loss (“Ozempic butt” mitigation) — emerging since ~2023; California Trim Clinic press release Feb 2026; Advanced Scripts Pharmacy frames CJC/ipa as the “lean-mass-preservation add-on” to semaglutide/tirzepatide.
  • Ipamorelin + BPC-157 / TB-500 recovery stacks — common in post-injury community. Community framing claims BPC-157 “upregulates the GH receptor,” a mechanistic claim repeated across the Greenfield/Campbell ecosystem with no published validation.

Peptide Sciences alone lists ≥7 ipa-containing blends (CJC/Ipa, ModGRF/Ipa, GHRP-2/Ipa, GHRP-6/Ipa, Sermorelin/Ipa, Tesa/Ipa, Tesa/CJC/Ipa). SKU density is unusual — ipa is the most-blended companion molecule in the catalog, exceeded only perhaps by BPC-157.

7B.7 Vendor and supply context

Pre-2024 vs post-2024 compounding-pharmacy landscape. Through 2024, Empower, Tailor Made, Hallandale, Olympia, Strive, and Wells Pharmacy Network all had ipamorelin programmes accessible through telehealth (Defy Medical, Marek Health, Cenegenics, BodyLogicMD, Hone, Eden, Maximus, Tucson Wellness MD, Vitalize Medical, PRAMAH/The Haven Tampa). The October 2024 PCAC vote forced ipamorelin into regulatory limbo where compounding access was effectively cut off or heavily curtailed through Q1 2025. Some clinics (Defy, Marek Health) continued listing CJC/ipa on formulary pages into 2026, though the regulatory-actual-supply status is in flux. As of early 2026 Huberman noted in the pre-recording update to the Koniver episode that CJC-1295, ipamorelin, and thymosin α-1 had been “re-allowed for prescription,” though community sources (PeptideVerdict, Onhealthcare.tech) caveat that no formal Federal Register update has been published.

Pricing arbitrage (community-observed):

  • Research-peptide 10/10 CJC-no-DAC + ipa blend: ~$50–$90 / vial (~1 month at 200 mcg/day)
  • Compounded clinic CJC/ipa pre-October 2024: $150–$400 / month
  • Post-PCAC grey market (effectively the research channel): same $50–$90, with reported volume increase
  • Telehealth platforms (Marek Health, Maximus, Defy) charging $99–$350/month inclusive of consultation and labs (formulary varies by quarter)

Reported QC issues. Underdosed batches (recurring complaint on r/Peptides, r/PeptideUmbrella; hard to confirm without third-party assay); DAC vs no-DAC mass-spec confusion (flagged in Peptide Catalog vendor guide; some vendors have allegedly shipped CJC-DAC blends labeled as no-DAC; mass-spec differential 3,649 Da vs 3,367 Da is diagnostic but most users lack access); blend-chromatogram ambiguity (Janoshik blend COAs report mass per component, no overall purity %; vendors publishing single “blend purity %” are flagged as red flag); FDA-level CoA inconsistency at the 503A nomination tier — the PCAC briefing noted nominators submitted CoAs that “refer to one BDS by name in the title and a different BDS by the molecular weight/formula.” Janoshik Analytical is the dominant third-party lab cited.

8. Safety Profile

  • Beck 2014 Phase 2 (n = 114). Most TEAEs mild–moderate and surgery-related. Notable imbalances vs placebo: hypokalemia (12.5% vs 3.4%), insomnia (10.7% vs 5.2%), hyperglycaemia at discharge (14.3% vs 8.6%). SAEs in 17.9% (ipa) vs 15.5% (placebo); 12 subjects had infection, 3 had anastomotic leak. Two fatal SAEs in the ipamorelin arm (both following colon-cancer resection complicated by anastomotic leak; primary causes hyperkalaemia/sepsis/perforated ulcer/renal failure). Causal attribution to drug was not established but the imbalance was flagged by FDA. ⚠️
  • Gobburu 1999. No specific AEs attributed.
  • FAERS through 30 September 2023. Two reports for compounded ipamorelin products: 32-year-old male with increased lacrimation/headache after a compounded ipamorelin nasal spray (illegal vendor source); 46-year-old male with arthralgia after a compounded ipamorelin + sermorelin injection for erectile dysfunction. Both non-serious. CAERS reported zero cases.
  • GH-class concerns (FDA-identified, applicable to any effective GH secretagogue): increased neoplasm risk, glucose intolerance / diabetes, intracranial hypertension, fluid retention, hypoadrenalism, hypothyroidism, slipped capital femoral epiphysis (paediatric), scoliosis progression, pancreatitis, QT prolongation (per macimorelin label).
  • Immunogenicity. FDA identified immunogenicity from peptide aggregates and synthesis impurities as a primary safety concern with compounded ipamorelin, particularly for subcutaneous administration.
  • Reproductive / embryonic toxicity. Class signal from ghrelin / ghrelin-antagonist mouse studies (Luque 2014); not directly demonstrated for ipamorelin.
  • Trial exclusion criteria (Beck 2014): Crohn’s disease history, complex bowel resections, IBS, cancer history outside the index resection, pregnancy, significant comorbidity. No paediatric data exist.
  • Community-reported AEs documented in §7B.4. None reach the FAERS-reporting threshold and none are individually well-characterised, but the volume of reports (injection-site, headache, fatigue, water retention) is consistent with a peptide in widespread sub-Q use.

9. Drug Interactions

No formally characterised human drug-interaction studies. Pharmacologically anticipated interactions:

  • Somatostatin / somatostatin analogs (octreotide, lanreotide, pasireotide): somatostatin tonically inhibits pituitary GH release and will blunt ipamorelin’s pharmacodynamic effect.
  • Glucocorticoids (chronic supraphysiological): blunt GH responsiveness to secretagogues at the somatotroph.
  • Insulin / oral antihyperglycaemics (metformin, GLP-1 RAs): theoretical antagonism of glycaemic control because GH is counter-regulatory; the Beck 2014 hyperglycaemia signal is consistent.
  • Levothyroxine / cortisol replacement: must be replete for normal GH-axis function (per Endocrine Society GHD evaluation guidance by extension).
  • Other GH secretagogues / GHRH analogs (sermorelin, tesamorelin, CJC-1295): commonly co-administered in non-medical compounding channels; no controlled human PK/PD or safety data exist for ipamorelin + CJC-1295 combinations despite their widespread non-prescription use.
  • Alcohol and opioids: preclinical ghrelin-pathway reward modulation raises a theoretical interaction; no human data.

10. Research Gaps

  1. No Phase 3 trial anywhere globally for any indication.
  2. No long-term (≥ 12 weeks) controlled human safety data at any dose for any indication.
  3. No published chronic-dosing IGF-1 trajectory in humans.
  4. Selectivity at supraphysiological / chronic doses unverified in independent human cohorts; foundational data 🔴 single-group.
  5. No paediatric data; FDA explicitly noted the absence in its PCAC analysis.
  6. No cancer-survivor population data; GH-axis stimulation in this population requires the safety inference structure used for recombinant GH (where labels carry neoplasm warnings).
  7. No controlled data on the ipamorelin + CJC-1295 combination despite its dominance in US compounding channels and the GLP-1 add-on use case.
  8. Reproductive / embryo-fetal toxicity uncharacterised; class signal from ghrelin pathway exists.
  9. Reinforcement / addiction potential identified as a theoretical concern by FDA; not characterised.
  10. Subcutaneous-route PK/PD never formally published; all human data are intravenous. The community uses sub-Q exclusively; the PK extrapolation from IV is unvalidated.
  11. No human data at community-typical sub-Q doses (100–300 mcg). Every published human study used IV doses an order of magnitude higher.

11. Bottom-Line Encyclopedia Note

Ipamorelin is a Novo Nordisk-discovered pentapeptide ghrelin-receptor (GHSR-1a) agonist with a single-group foundational dataset (Raun 1998) 🔴 supporting selective GH release without significant cortisol, ACTH, or prolactin elevation in healthy male volunteers and swine. Helsinn developed it for postoperative ileus through a 117-patient Phase 2 trial (Beck 2014, NCT00672074) that failed its primary endpoint; development was discontinued. No regulatory authority has approved ipamorelin for any indication. The FDA placed it on §503A Category 2 in September 2023; in October 2024 the Pharmacy Compounding Advisory Committee voted 0–12–1 against inclusion on the 503A bulks list, and ipamorelin remains outside the legal US compounding pathway as of May 2026. Prohibited at all times in sport under WADA 2026 S2.2.4; Schedule 4 with Appendix D possession restriction under the Australian Poisons Standard. Community use is widespread (Community Tier A) despite the absence of any controlled long-term human data and a 10× dose disconnect between trial and clinic/community dosing.

11B. Gap Analysis — Where Science and Community Diverge

Ipamorelin is the canonical case for the 4-cell “High community + Low science” gap pattern matrix introduced in v4 of this methodology. The compound sits simultaneously in three of the four subclasses: #2 (tested negative or mixed), #3 (indication divergence), and #4 (research dose substantially above community dose). This triple-subclass occupancy is what makes ipamorelin distinctive — it is not merely a “community-ahead-of-science” peptide in the BPC-157 sense (where no human trial exists at all), it is a peptide that has been in humans, in a registrational Phase 2 trial, that failed its primary endpoint for an indication the community does not care about, at a dose 10× higher than the community uses, leaving the community use case (body composition, recovery, sleep, anti-aging) never tested in any human study at any dose.

11B.1 Subclass #2 — Tested negative

TopicScienceCommunityGap
Postoperative ileus (the tested indication)Beck 2014 / NCT00672074: Phase 2 n=114, primary endpoint missed (25.3 h vs 32.6 h, P > 0.05). Helsinn discontinued development. Two fatal SAEs in the ipamorelin arm, causal attribution not established, imbalance flagged by FDA. ⚠️POI is not the community use case; rarely discussed.🟢 Layer-aligned but reader-disconnected. Trial readers and community readers are talking about different things. The community typically does not know the only human Phase 2 trial existed or failed.

11B.2 Subclass #3 — Indication divergence

TopicScienceCommunityGap
Body composition / recovery / sleep / aging — the community use caseNo controlled human evidence at any dose. No RCT, no observational, no Cochrane. Aged-rodent and ferret data exist for GI-motility and cisplatin-induced weight loss; tilapia HPG axis. None is the community indication.Codified protocol (100–300 mcg sub-Q, 1–3×/day, 5-on/2-off, 8-on/8-off); widespread claimed benefits in sleep, recomp, recovery, skin, fat loss.🔴 Untested. The molecule has been in humans (Gobburu 1999 PK/PD; Beck 2014 POI Phase 2), but the community indication has zero direct human trial data. The reader inference “ipamorelin is a tested peptide” is technically true; “ipamorelin has been tested for what the community uses it for” is false.
Selectivity at supraphysiological / chronic dosesSelectivity claim (no cortisol/ACTH/prolactin rise) derives entirely from Raun 1998 swine + small healthy-volunteer cohort, single Novo Nordisk group. 🔴 No independent human replication. Mendias 2026 and Coutinho 2026 reviews both flag that selectivity has been demonstrated only under short-term controlled dosing.Treated as ipamorelin’s defining property; the reason the community prefers ipa over GHRP-2/6.🔴 The most-cited community advantage of ipamorelin rests on unreplicated single-group data. Community-channel materials cite Raun’s selectivity result as if it were established class consensus; it is one paper from one group in 1998.
Skin / sleep / “glow” / longevityNo human RCT for any of these endpoints.Widespread claims (sleep is the most consistent; skin and “glow” are heavy in clinic marketing).🟡 Untested for community-relevant effects. Sleep claim has biological plausibility (nocturnal GH-pulse synchrony) but no controlled-sleep-architecture study has been conducted with ipamorelin.

11B.3 Subclass #4 — Research dose : community dose disconnect

CompoundResearch dose (cited paper)Community dose (cited source)RatioPredictable consequence
Ipamorelin0.03 mg/kg IV (Gobburu 1999, Beck 2014) ≈ 2.4 mg per dose in 80 kg adult100–300 mcg sub-Q (Greenfield, Campbell, Koniver, ExcelMale, telehealth standard)~10× (research dose 8–24× community per-injection dose)“No IGF-1 movement on bloodwork” complaints at 100–200 mcg sub-Q are predictable from the dose gap, not necessarily evidence the molecule is inactive. Community SME BigTex on ExcelMale: “500 mcg of ipamorelin is the starting point if you want to see your GH and IGF-1 levels rise.”

Interpretation. The 10× ratio is the largest dose disconnect identified in the GH/GHRH/GHS class so far (cf. sermorelin ~3–4×; tesamorelin ~1× because it has an approved indication and the regulated dose matches the community dose). Three things follow:

  1. Most users at 100–200 mcg sub-Q are receiving a fraction of the dose that drove the only published human PK/PD data. Even if the molecule were active for the community indication (untested), the typical community dose is below the tested range.
  2. The community-internal IGF-1 dispute is the predictable consequence. Half the community reports no IGF-1 movement; the other half says you need 500 mcg+. Both can be right: 100–200 mcg may be sub-threshold for IGF-1 detectability while still producing a GH pulse (which is what Gobburu 1999 actually demonstrated, at much higher IV doses).
  3. The community “no effect / wasted money” outcome that surfaces in long logs is informationally compatible with both “the molecule doesn’t work for this indication” and “the molecule may work but the dose is too low to test.” The Pass 1 evidence base cannot distinguish.

11B.4 Cross-subclass items

TopicScienceCommunityGap
CJC-1295 + ipamorelin combination — the dominant use caseNo peer-reviewed PK/PD or safety study of the fixed combination. Each compound studied in isolation.The combination is the de facto standard; premixed 10/10 blend vials are the dominant SKU; “GHRH + GHRP synergy” is the canonical mechanistic framing.🔴 Community uses the combination as a standard while no controlled trial of the combination has been conducted. The synergy claim is mechanistically plausible (GHRH + GHRP do produce a larger GH pulse than either alone in animal models) but the human dose-response, safety, and efficacy of the specific fixed-blend community use case is uncharacterised.
Sub-Q PK/PDAll published human data are IV. Sub-Q PK has never been formally published.Sub-Q is the exclusive community route.🔴 The route used by 100% of the community has never been published in a human study.
WADA / anti-doping awarenessS2.2.4 banned at all times.Aware (named in most vendor pages and Innerbody-style consumer guides) but underweighted in clinic discussions.🟡 Awareness present but salience low. Anyone subject to NCAA, USADA, WADA, or DoD-OPSS jurisdiction needs this before the first dose.
Single-group dependency on the selectivity claim🔴 Raun 1998 + the small Gobburu 1999 healthy-volunteer dataset are the entire human and primary preclinical foundation. No independent replication in 28 years.Selectivity is treated as established class consensus.🔴 Community is unaware of the single-group dependency. The clinical marketing framing of ipamorelin’s “clean” profile inherits from one paper from one group from one decade.
2024 PCAC vote0–12–1 against §503A inclusion; FDA cited inadequate characterisation, immunogenicity concerns, and absence of supporting safety/efficacy data.Three-way internal split: compounding pharmacies treat it as regulatory overreach; research-peptide vendors absorb displaced demand; skeptical biohacker minority accepts the PCAC decision. The “ipamorelin is back” framing in early-2026 telehealth marketing is overselling — no Federal Register update has confirmed re-listing.🟡 Both layers concur the vote happened and the evidence base is thin. Disagreement is on what to conclude operationally.

11B.5 Net characterisation

Ipamorelin sits in the “High community + Low science, indication divergence with dose disconnect” subclass of the gap-pattern matrix — a distinct flavor from BPC-157 (community ahead, no approval anywhere), SS-31 (FDA approval halo over thin general-use case), or sermorelin (FDA approval halo, regulatory pedigree on a 1990s trial cluster that hasn’t been refreshed). Unlike SS-31, ipamorelin has no FDA approval to lend inferential support. Unlike sermorelin, ipamorelin has no FDA-approved historical brand to anchor a §503A compounding pathway. Unlike BPC-157, ipamorelin has been in human trials — but the trial that exists tested an indication the community doesn’t care about, at a dose an order of magnitude above what the community uses, and missed its primary endpoint.

The two highest-consequence gaps for an optimization-audience reader:

  1. The community use case (body composition / recovery / sleep / longevity) has zero human controlled data at any dose. Aged-rodent and ferret data don’t address it. The closest human signal is the Beck 2014 hyperglycaemia and hypokalemia imbalance, which is a safety signal not an efficacy signal, and which was generated at IV doses 10× the community standard.
  2. The clinic-prescribed 100–300 mcg sub-Q dose is below the dose that generated the only published human PK/PD data, and the community-internal IGF-1 dispute is the predictable consequence. Reader inference: “no IGF-1 movement at 200 mcg” does not establish that ipamorelin is inactive; it establishes that the community dose is at or below the IGF-1 detection threshold in untrained users.

12. Three Paths

Definition, not prescription. The reader chooses the bar; the monograph names where the molecule currently sits relative to each.

Conservative path. Defined as engaging only after (a) peer-reviewed publication of an adequately powered RCT of ipamorelin in healthy adults with body-composition, recovery, sleep-architecture, or longevity endpoints; (b) marketing authorisation for ipamorelin in any indication in a major jurisdiction (FDA, EMA, MHRA, PMDA, TGA, Health Canada); (c) independent human replication of the Raun 1998 selectivity finding 🔴; or (d) a positive Cochrane systematic review of GHS use in healthy adults. None of these gates is currently met. Ipamorelin does not meet the conservative bar. For athletes subject to WADA, NCAA, USADA, or DoD-OPSS jurisdiction, ipamorelin is named on the 2026 Prohibited List S2.2.4 with banned-at-all-times status; the conservative path is mandatory, not optional.

Moderate path — clinic / telehealth, IGF-1-titrated, with informed-consent on the gap structure. Defined as engaging through a licensed prescriber on a 503A-pathway product where one is currently available — operationally, this means a US compounding-pharmacy / telehealth combination that has continued to dispense post-PCAC under whatever interim mechanism applies (the regulatory status as of May 2026 is in flux; no formal Federal Register update has confirmed re-listing of ipamorelin on the 503A bulks list as of 2026-05-16). The canonical clinic protocol: 100–300 mcg sub-Q nightly, pre-bed on empty stomach, 5 nights/week, 8 weeks on / 8 weeks off; almost always paired with CJC-1295 no-DAC. Baseline bloodwork (IGF-1, fasting glucose, HbA1c, lipid panel, CBC, CMP, PSA in men); on-cycle monitoring at 8–12 weeks (IGF-1 most importantly, with awareness that the clinic dose may be sub-threshold for lab-detectable IGF-1 movement; community SME consensus is that ≥500 mcg is needed to see lab change). Informed-consent items the prescriber should surface: the community indication has never been tested in humans; the selectivity claim is single-group; the CJC + ipa combination has never been studied as a fixed product; the dose used is ~10× below the dose that drove the only published human study. Drug-testing exposure: the moderate path collapses to the conservative path for any athlete subject to WADA, NCAA, USADA, or DoD-OPSS jurisdiction — ipamorelin is explicitly named on the 2026 List S2.2.4, no TUE precedent is documented, and Global DRO returns “Prohibited at all times” in all queried jurisdictions.

High-tolerance path — research-channel sourcing with community mitigation stack. Defined as acknowledging that (a) no conservative gate is met, (b) the community use case has zero human RCT data, (c) the dose used is an order of magnitude below the only published human study, (d) the legal §503A pathway is closed in the US as of May 2026, (e) the WADA banned-at-all-times status is absolute, and (f) the foundational selectivity claim rests on a single research group. The community mitigation stack documented in §7B: third-party COA verification (Janoshik or equivalent — vendor-published COAs without verification keys are flagged); reconstitution in bacteriostatic water with the 3 mL / 10 mg blend convention (33 mcg/U-100 unit); structured baseline + on-cycle bloodwork (IGF-1, fasting glucose, HbA1c, CBC, CMP) at minimum; awareness that the clinic dose (100–300 mcg) may produce no IGF-1 movement and that the community-internal IGF-1 dispute is the predictable consequence; avoidance of the DAC variant of CJC-1295 in combination (the Greenfield / Campbell consensus, supported by mechanistic mismatch); cycling 8 weeks on / 8 weeks off rather than open-ended; physician-monitoring dialogue even where the physician has not prescribed; if no effect is observed at 200 mcg by 8–12 weeks, the dose-disconnect framing recommends against escalation toward 500+ mcg as a default — that path produces tachyphylaxis at the somatotroph level (per Gobburu 1999’s own observation) and exits the dose range the foundational selectivity claim was based on.

The “FDA-approved” framing occasionally found in ipamorelin clinic and vendor copy is not applicable. Ipamorelin has never been FDA-approved for any indication. The “investigated by Novo Nordisk and Helsinn” framing is true but does not establish efficacy for the community indication — Helsinn’s investigation produced one Phase 2 trial that failed its primary endpoint, after which development was discontinued.

13. Key References

Science (Pass 1 layer)

Peer-reviewed primary literature

  • Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol 1998;139(5):552–61. PMID 9849822. DOI 10.1530/eje.0.1390552. ⚠️ 🔴
  • Gobburu JV, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res 1999;16(9):1412–6. PMID 10496658. ⚠️ 🔴
  • Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis 2014;29(12):1527–34. PMID 25331030. NCT00672074. ⚠️
  • Lu Z, Ngan MP, Liu JYH, et al. The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets. Physiol Behav 2024;284:114644. PMID 39043357. ⚠️
  • Gouda M, Ganesh CB. The influence of ghrelin agonist ipamorelin acetate on the hypothalamic-pituitary-testicular axis in a cichlid fish. Anim Reprod Sci 2024;268:107550. PMID 38996787.

Peer-reviewed reviews 2026 (narrative)

  • Mendias CL, Awan TM. Safety and efficacy of approved and unapproved peptide therapies for musculoskeletal injuries and athletic performance. Sports Med 2026. PMID 41966639.
  • Mayfield CK, Bolia IK, Feingold CL, et al. Injectable peptide therapy: a primer for orthopaedic and sports medicine physicians. Am J Sports Med 2026;54(1):223–9. PMID 41476424.
  • Rahman OF, Lee SJ, Seeds WA. Therapeutic peptides in orthopaedics. J Am Acad Orthop Surg Glob Res Rev 2026;10(1). PMID 41490200.
  • Coutinho LFD, et al. A new era of doping? Peptide and peptide-analog drugs in sport. J Sports Med Phys Fitness 2026. PMID 41880199.
  • Mavrych V, Shypilova I, Bolgova O. Therapeutic peptides in gerontology. Front Aging 2026;7:1790247. PMID 42021992.
  • Renke G, Chinellato L. Therapeutic peptides in aesthetic, metabolic and endocrine conditions. Int J Mol Sci 2026;27(9):3890. PMID 42123471.

Regulatory documents

  • US FDA. Final Summary Minutes, PCAC Meeting, 29 October 2024 (FDA document 185412). Vote 3b: Ipamorelin (free base) — 0 Yes / 12 No / 1 Abstain. Vote 3c: Ipamorelin acetate — 0 Yes / 12 No / 1 Abstain.
  • US FDA. Briefing Document, PCAC Meeting, 29 October 2024 — Ipamorelin-related bulk drug substances (FDA document 182088).
  • US FDA. Bulk Drug Substances Used in Compounding under §503A — Interim List, updated 14 May 2026 (FDA document 94155).
  • US FDA. Interim Policy on Compounding Using Bulk Drug Substances under §503A; Final Guidance, 7 January 2025.
  • US FDA. Notice of PCAC meeting 23–24 July 2026 (Docket FDA-2025-N-6895; Fed Reg 2026-07361, 16 April 2026) — agenda includes BPC-157, KPV, TB-500, MOTs-C, DSIP/emideltide, Semax, Epitalon; ipamorelin not on agenda.
  • TGA. Scheduling Delegate Interim Decisions, ACCS/ACMS February 2016 — ipamorelin added to Poisons Standard as a PIED; Schedule 4 with Appendix D possession restriction.
  • TGA. Therapeutic Goods (Poisons Standard — October 2025) Instrument 2025.

Anti-doping documents

  • WADA. 2026 Prohibited List, in force 1 January 2026. Section S2.2.4 “Growth Hormone Releasing Factors — growth hormone secretagogues and their mimetics” — ipamorelin specifically named.
  • Global DRO ipamorelin record — queried 2026-05-16, all jurisdictions “Prohibited at all times.”
  • NCAA 2025–26 Banned Drug Class List — Peptide Hormones, Growth Factors, Related Substances and Mimetics.
  • DoD Operation Supplement Safety — Peptide hormones advisory.
  • BSCG 2026 commentary — ipamorelin named as contaminant of concern.

Clinical trial registry

  • NCT00672074 — Ipamorelin in Ileus (Helsinn Therapeutics; Phase 2; completed; primary endpoint negative; published Beck 2014).
  • NCT00601679 — Helsinn-sponsored ipamorelin POI study; terminated; results not posted.
  • NCT01280344 — additional ipamorelin study in bowel resection patients; no peer-reviewed publication.

Academic secondary sources

  • DrugBank DB12370 (Ipamorelin).
  • PubChem CID 9831659.
  • IUPHAR/BPS Guide to Pharmacology (ghrelin receptor agonist class).

Community (Pass 2 layer)

Substantive retrieval-limitations disclosure carried into §7B. Key named community sources cited in this composition:

  • DatBtrue writeups (Austeroids archive of 2008–2012 originals)
  • AnabolicMinds “Ipamorelin vs Sermorelin” thread
  • EliteFitness “Ipamorelin and CJC 1295” thread
  • ExcelMale threads: “Ipamorelin and CJC-1295 (no dac) Plan”; “Ipamorelin only did the trick for me”; “CJC-1295/Ipamorelin (10mg) blend dosage”; “Ipamorelin Dosage Discussion”; “Ipamorelin and IGF-1” (BigTex thread); “Lecture: What You Should Know About CJC-1295 with Ipamorelin, PT-141, and BPC-157”
  • Huberman Lab “Benefits & Risks of Peptide Therapeutics” (April 2024); Huberman Lab #156 with Dr. Craig Koniver (October 2024)
  • Peter Attia Drive #274 with Derek MPMD
  • Derek MPMD Substack “The Complete Guide to Growth Hormone Secretagogues After 40 (Or 30)”
  • Ben Greenfield Life “Wolverine Peptide Stack”; Ben Greenfield peptide resource pages
  • Jay Campbell “Mod GRF 1-29 vs CJC-1295”; “CJC-1295 for Weight Loss, Muscle Growth and Bodybuilding”
  • Peptide Sciences product pages and blend catalog
  • Swolverine; Innerbody; PeptideDeck; PeptideDosages.com; Peptides.org; SeekPeptides; Valhalla Vitality; Elements Arms; The Peptide Catalog (multiple articles); The Peptide List Substack “The Evidence Gap”
  • Perfect B clinic protocol page; Marek Health; Defy Medical
  • Eternal Peptides; Panda Peptides COA hub; Chameleon Peptides; Vantixbio Janoshik-reading guide; Janoshik Analytical
  • APC (Alliance for Pharmacy Compounding) PCAC commentary; OneTwenty “Best Peptide Companies”; Onhealthcare.tech “Category 2 Peptide Unwind”; PeptideVerdict “FDA Peptide Status 2026”; Safe Harbor Group “FDA’s Overreach on Compounded Peptides”
  • Advanced Scripts Pharmacy “Peptide Stacking 101”; California Trim Clinic PR (Feb 2026) — “Ozempic butt” / lean-mass-preservation framing
  • FastLifeHacks Huberman Peptide List

Full numbered citation list with URLs and access dates in source file ipamorelin_com_2026-05-16_A80.md.

Retrieval-limitations disclosure (carried from Pass 2 §9). Reddit thread-level evidence at named-source resolution was not retrievable at this pass — community texture relies on ExcelMale, EliteFitness, and AnabolicMinds as the canonically-cited bodybuilding/TRT forums, plus the biohacker-publication and clinic-page ecosystem. Joe Rogan, Tim Ferriss, FoundMyFitness, Rhonda Patrick podcasts not directly cited at episode-specific resolution. Pre-2024 compounding-pharmacy SKU pages largely accessible only through Wayback Machine; not queried in this pass. “DatBtrue” original posting threads reconstructed from a third-party Austeroids republication; original ProfessionalMuscle / MESO-Rx threads not directly retrievable at named-source resolution today. These gaps are common to any 2026 Pass-2 retrieval against community sources; reliability rests on the named forum threads, biohacker-publication ecosystem, and explicit vendor/clinic page citations.

14. Audit / Refresh Trail

  • Composed: 2026-05-18
  • Science-layer source: ipamorelin_sci_2026-05-16_D10.md (Pass 1; refresh date 2026-05-16; prior coverage in Group_B_GH_GHRH_Secretagogues_2026-05-09.md and Growth_Hormone__GHRH_Analogues__and_GH_Secretagogues__Comprehensive_Scientific_and_Regulatory_Review_2026.md)
  • Community-layer source: ipamorelin_com_2026-05-16_A80.md (Pass 2; compiled 2026-05-16)
  • Section 4 Last regulatory review: 2026-05-16
  • Two-molecule calibration block: Not applicable — ipamorelin is a single canonical molecule (H-Aib-His-D-2-Nal-D-Phe-Lys-NH₂ pentapeptide). The NNC 26-0161 / NN703 / NNC-26-0703 lay-literature confusion is a naming-conflation issue, not a two-molecule structural ambiguity, and is handled in §1 and §2.
  • Gap-matrix subclass assignment (v4): Subclass #2 (tested negative — POI) + Subclass #3 (indication divergence — community body-composition use case never tested) + Subclass #4 (research dose : community dose ~10×). All three subclasses surfaced explicitly in §11B. Ipamorelin is the canonical case for v4 subclass #3 and a primary case for subclass #4 (along with sermorelin at ~3–4×).
  • Next refresh triggers:
    • Any modern multi-center RCT of ipamorelin in healthy adults (largest possible evidence-base shift)
    • Any updated Cochrane SR of GHS use in healthy adults
    • Any change to WADA Prohibited List Section S2.2.4 (annual cycle, effective 1 January)
    • Any FDA action affecting §503A or §503B compounding access for ipamorelin (e.g., a future PCAC re-nomination, a Federal Register update on the bulks list, or a re-categorisation)
    • Any change to TGA scheduling of ipamorelin or related GHS
    • Any further Helsinn / Stealth / Novo Nordisk / successor regulatory filings (e.g., a new sponsor re-application; Helsinn’s 2014 development discontinuation has remained in force)
    • Any high-profile WADA sanction with ipamorelin as the named substance
    • Material shift in the grey-market vendor landscape (further FDA enforcement, vendor scandals, COA failures)
    • Any new mainstream-podcast or named-figure endorsement or repudiation (Huberman, Attia, Rogan, Greenfield, Campbell, MPMD, Koniver)
    • Any peer-reviewed Reddit-corpus retrieval that closes the Pass 2 retrieval gap
    • Any new published characterisation of community-reported tachyphylaxis or IGF-1 dose-response in sub-Q ipamorelin dosing
    • Any positive Phase 3 readout from related GH/GHRH/GHS class members (tesamorelin lipodystrophy, anamorelin cancer cachexia) that updates the class-level evidence