Section 01
What it's used for
Boosting growth hormone release
MOD-GRF-1-29 is most often combined with ipamorelin or GHRP-2/6, other growth-hormone-stimulating compounds, in research protocols. Together they are studied for boosting the body's natural bursts of growth hormone release.
▸Clinical wording
Most commonly used as the GHRH component in combination protocols with ipamorelin or GHRP-2/6 for physiological GH pulse amplification.
Muscle and fat changes
In research combining MOD-GRF-1-29 with other growth-hormone-releasing peptides, studies report increased lean muscle mass, reduced fat mass, and better recovery from exercise or injury within these combination protocols.
▸Clinical wording
Research shows improved lean mass, reduced fat mass, and enhanced recovery when used in combination secretagogue protocols.
Boosting nighttime hormone release
Taking MOD-GRF-1-29 before bed is studied for amplifying the body's own natural growth hormone pulse that occurs overnight, since growth hormone release naturally peaks during the deepest stages of sleep each night.
▸Clinical wording
Pre-bedtime administration amplifies the natural nocturnal GH pulse.
Countering age-related hormone decline
MOD-GRF-1-29 is being studied for somatopause, the natural age-related decline in growth hormone, by amplifying the body's own pulses of growth hormone release rather than replacing the hormone directly with injections.
▸Clinical wording
Addresses somatopause by amplifying endogenous GH pulsatility.
Section 02
Mechanism of Action
A shortened hormone rebuilt to last
- Only the first 29 building blocks of the natural releasing hormone are needed to keep its activity.
- A blood enzyme cuts that fragment near one end, and swapped building blocks block the cut.
- Imaging shows it inserting as a helix, with one anchoring contact worth roughly 200-fold in potency.
- The modified version resisted the enzyme in the dish and released growth hormone from rat pituitary cells.
▸Clinical wording
GHRH receptor engagement by the 1-29 core
GHRH(1-29)-NH2 is the shortened fragment that retains releasing activity, and in human plasma it is cleaved by dipeptidyl peptidase IV at the 2-3 bond; a D-amino acid at position 1 or 2 blocks that hydrolysis. Cryo-EM of the activated human receptor shows the peptide as an alpha helix with its C-terminus on the extracellular domain and its N-terminus buried in the transmembrane core: Tyr1 hydrogen-bonds inside the pocket, Ala2 adds hydrophobic contacts, and Asp3 forms a salt bridge with Lys182 whose mutation cuts potency roughly 200-fold. Mod GRF (1-29) is a tetrasubstituted hGRF(1-29) backbone shown in vitro to resist DPP-IV and to release GH from cultured rat anterior pituitary cells.
The signal that refills the stores
- Binding starts a cascade of messengers inside the hormone-producing cells of the pituitary.
- The final relay switches on the growth hormone gene, so stores are rebuilt rather than only emptied.
- The same relay also raises production of the receptor the peptide binds to.
▸Clinical wording
Gs-coupled cAMP, PKA and CREB signalling in somatotrophs
The GHRH receptor is a 423-amino-acid class B G-protein-coupled receptor. Ligand binding lets it couple to Gs, which activates adenylate cyclase and raises intracellular cAMP; cAMP then activates protein kinase A, which phosphorylates CREB. Phosphorylated CREB binds cAMP response elements in the GH gene promoter and can induce the pituitary-specific transcription factor Pit-1, so that hormone stores are rebuilt rather than only emptied, and CREB also drives transcription of the receptor itself. MAPK/ERK and PI3K/Akt activation have been described downstream in the same tissue.
Electric charge releases stored hormone
- The messenger opens a channel that changes the cell's electrical charge and lets calcium flood in.
- Calcium makes the cell dump packets of growth hormone it had already made.
- So the immediate effect is release of stored hormone, not fresh production.
- In mice lacking the natural hormone, long stimulation grew the pituitary cells and normalised body size.
▸Clinical wording
Depolarization-driven calcium influx and granule exocytosis
The same cAMP rise opens a sodium channel and depolarizes the somatotroph, which opens voltage-dependent calcium channels; calcium entry triggers exocytosis of GH already held in secretory granules, so the acute response to receptor activation is release of preformed hormone rather than new synthesis. Sustained receptor stimulation is also trophic: in GHRH-knockout mice a long-acting analogue built on the same GRF backbone raised total pituitary RNA and GH mRNA with immunohistochemical evidence of somatotroph proliferation, and normalized body weight and length.
The brake that sets the timing
- In humans the timing of hormone bursts follows the lifting of a braking signal from the brain.
- The response to a six-hour infusion faded, while the response to another trigger kept working.
- Release stayed in waves even under continuous infusion lasting up to fourteen days.
- A separate family of releasing peptides counters that brake and works together with this one.
▸Clinical wording
Somatostatin tone and the ghrelin-receptor synergy
In humans GH bursts appear to be timed by withdrawal of hypothalamic somatostatin: the response to exogenous GHRH varies with somatostatin tone, attenuates during a six-hour GHRH infusion while the response to hypoglycaemia does not, and stays pulsatile under continuous GHRH infusion lasting up to 14 days. The GH-releasing hexapeptides act through a separate receptor, appear to antagonize somatostatin functionally, and synergize with GHRH; that synergy in humans requires endogenous GHRH, and intravenous GHRP releases more GH than GHRH in humans while the reverse holds in vitro.
What the released hormone does next
- Released growth hormone docks on its own receptor and starts a relay inside target cells.
- The liver's output of a growth factor is the measurable result throughout the body.
- In healthy adults a related long-acting analogue raised hormone two- to tenfold and the growth factor up to threefold.
- Overnight sampling showed the wave pattern unchanged while the baseline between waves rose sharply.
▸Clinical wording
Downstream GH receptor JAK2/STAT5 signalling
Secreted GH acts on the growth hormone receptor, whose activation drives JAK2 and, through it, STAT1, STAT3 and STAT5, alongside a JAK2-independent Src arm and SOCS-mediated negative feedback; hepatic IGF-1 output is the systemic readout. In healthy adults, single subcutaneous doses of the albumin-binding analogue built on this GRF backbone raised mean plasma GH two- to ten-fold and IGF-1 1.5- to three-fold. Overnight sampling after one injection showed pulse frequency and amplitude unchanged while trough GH rose 7.5-fold and IGF-1 rose 45%.
Section 03
Biological Pathways
- GHRH-R engagement and DPP-IV resistanceCryo-EM shows the peptide as a helix binding the receptor's transmembrane core; a tetrasubstituted backbone resists cleavage by dipeptidyl peptidase IV, the enzyme that inactivates native GHRH within minutes.
- Gs/cAMP/PKA/CREB transcriptionReceptor coupling to Gs raises cAMP, activating PKA, which phosphorylates CREB; CREB then binds the GH gene promoter and induces Pit-1, rebuilding hormone stores rather than only emptying them.
- Calcium-driven exocytosis of stored GHThe same cAMP rise depolarizes the somatotroph and opens voltage-dependent calcium channels, triggering exocytosis of GH already held in secretory granules as the acute release response.
- Somatostatin withdrawal and ghrelin synergyGH pulses appear timed by falling hypothalamic somatostatin tone, and the separate ghrelin-receptor pathway of secretagogues synergizes with GHRH, an interaction that in humans requires endogenous GHRH.
- Downstream GH/JAK2/STAT5/IGF-1 axisSecreted GH activates its receptor's JAK2 and STAT5 signaling; single subcutaneous doses of an albumin-binding analogue on this backbone raised trough GH 7.5-fold overnight and IGF-1 by 45% in healthy adults.
Section 04
Dosage Information
Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — sermorelin label | FDA label for sermorelin, the unmodified parent peptide | 30 µg/kg at bedtime once daily — about 2.1–2.7 mg for a 70–90 kg adult; the same label's test dose is 1 µg/kg into a vein | That is the parent peptide, dosed in children with growth failure and withdrawn in 2008. The four changes slow its breakdown, so the doses do not carry across. |
| Intravenous | 1993 dose-response study in 30 healthy men | 0.25–2 µg/kg once — about 18–180 µg for a 70–90 kg adult. Growth hormone peaked at 1–2 µg/kg and stayed up about three hours | One injection of the unmodified peptide, one hormone measured. Above 2 µg/kg more adds nothing — a ceiling, not a repeat schedule or a clinical effect. |
| Intranasal | The same 1993 study — the only data for this route | 3–5% of a nasal dose reached the blood; matching 1 µg/kg into a vein took about 50 µg/kg — 3.5–4.5 mg for a 70–90 kg adult | A mix made for that study, with the unmodified peptide. Sprays sold as mod GRF 1-29 give about 20 µg per puff, so a whole 2 mg bottle is short of one such dose. |
| Subcutaneous — self-administration | Self-administration, usually sold as "CJC-1295 no DAC" | 100–300 µg per injection, one to three times a day, usually with a growth-hormone releaser — about 1.1–4.3 µg/kg for 70–90 kg | Practice, not a finding: never given in a human trial; the 30-minute half-life comes from rats and dishes. The name also drags in the DAC form's weekly dosing. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Lyophilised powder
MOD-GRF (1-29) is supplied as a lyophilised powder kept at -20°C for 18-24 months or at 2-8°C for 3-6 months. It is usually reconstituted with bacteriostatic water. The four substitutions in its sequence give it resistance to breakdown by DPP-4.
After reconstitution
The reconstituted solution is kept at 2-8°C and used within 21 days. Its biological half-life is short, around 30 minutes, once it is administered.
Section 07
Side Effects & Precautions
Facial flushing and warmth (15-30 minutes post-injection). Mild headache. Water retention with sustained use. Injection site reactions. No significant cortisol or prolactin effects. Hypoglycemia rare.
Section 08
Regulatory Status
It remains a research peptide: no approved label, indication, dose or established human safety profile exists for this specific, modified analogue.
FDA / United States
Not approved
In 2023 the FDA had assigned CJC-1295 to Category 2 of the interim 503A bulk-substances list and removed it in April 2026 after the nomination behind it was withdrawn; removal from Category 2 is not addition to the 503A Bulks List. Mod GRF (1-29) is not on that list, so section 503A opens no lawful compounding route.
Not Sermorelin (Geref)
A different history
The unmodified GRF(1-29) fragment was once FDA-approved as Geref for diagnosing growth-hormone deficiency, then discontinued in 2008 for commercial reasons. Mod GRF (1-29) is a separately engineered, more stable analogue that never went through its own approval process.
EU / EMA
Not approved
Mod GRF (1-29) has no EU marketing authorisation and does not appear among medicines evaluated by the CHMP.
WADA
Prohibited under S2
As a growth-hormone-releasing-hormone analogue, mod GRF (1-29) / CJC-1295 falls under category S2 (Peptide Hormones, Growth Factors and Related Substances) — banned at all times, in and out of competition, with no therapeutic-use exemption.
Clinical trials
Human data covers a different molecule
Published Phase I/II trials (Teichman et al., 2006) and an HIV-lipodystrophy study (NCT00267527) tested CJC-1295 with DAC, the long-acting, albumin-linked version — not the unlinked mod GRF (1-29) itself, which has no dedicated human trial of its own.
A «research use only» label does not turn mod GRF (1-29) into an approved medicine and says nothing about its purity. Regulatory status differs between jurisdictions and changes over time — check the current documents of your own regulator before relying on any of this.
Section 09
Research Studies
- [1]Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasmaFrohman LA, Downs TR, Heimer EP, Felix AM. · Journal of Clinical Investigation · 1989
- [2]Structural basis for activation of the growth hormone-releasing hormone receptorZhou F, Zhang H, Cong Z, et al. · Nature Communications · 2020
- [3]Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF AnalogJette L, Leger R, Thibaudeau K, et al. · Endocrinology · 2005
- [4]Growth hormone-releasing hormone receptor (GHRH-R) and its signalingHalmos G, Szabo Z, Dobos N, Juhasz E, Schally AV. · Reviews in Endocrine and Metabolic Disorders · 2025
- [5]Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouseAlba M, Fintini D, Sagazio A, et al. · American Journal of Physiology - Endocrinology and Metabolism · 2006
- [6]Physiological role of somatostatin on growth hormone regulation in humansThorner MO, Vance ML, Hartman ML, et al. · Metabolism · 1990
- [7]History to the discovery of ghrelinBowers CY. · Methods in Enzymology · 2012
- [8]The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological AspectsDehkhoda F, Lee CMM, Medina J, Brooks AJ. · Frontiers in Endocrinology · 2018
- [9]Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adultsTeichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. · The Journal of Clinical Endocrinology & Metabolism · 2006
- [10]Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analogIonescu M, Frohman LA. · The Journal of Clinical Endocrinology & Metabolism · 2006
Section 10
Frequently Asked Questions
MOD-GRF (1-29) is the tetrasubstituted GHRH(1-29) fragment sold as "CJC-1295 without DAC": the same four amino-acid substitutions resist enzymatic breakdown, extending the half-life from about 5-7 minutes for native GHRH to roughly 30 minutes. CJC-1295 with DAC adds a Drug Affinity Complex that binds albumin, stretching action out for days and producing sustained GH elevation, whereas MOD-GRF (1-29) clears fast and produces a single acute pulse instead.
In vitro and in cultured rat pituitary cells it releases GH by activating the GHRH receptor, but the human trials in its own research record were run on native unmodified GHRH(1-29) or on CJC-1295 with the DAC extension, not on the no-DAC tetrasubstituted peptide itself. No published human trial has dosed MOD-GRF (1-29) specifically and measured GH output; what exists is receptor pharmacology plus a different molecule's clinical data.
Self-administration outside any trial runs at 100-300 µg per injection, one to three times a day, usually alongside a GH-releasing peptide like ipamorelin - roughly 1.1-4.3 µg/kg for a 70-90 kg adult. That range has never been tested in a human study; the 30-minute half-life behind the dosing schedule comes from rat and cell-culture work, not from people.
MOD-GRF (1-29) activates the GHRH receptor, while ipamorelin and similar GH-releasing hexapeptides work through a separate receptor that appears to counter somatostatin's inhibitory tone; combining the two is proposed to produce a larger GH pulse than either alone. This synergy is described from receptor pharmacology and animal work rather than from a human trial comparing the combination against either agent alone.
Facial flushing and warmth 15-30 minutes after injection, mild headache, water retention with sustained use, and injection-site reactions are described, alongside no significant effect on cortisol or prolactin and rare hypoglycaemia. No formal human safety trial of this specific analog underlies that list; it reflects the reporting pattern for GHRH-analog use generally.
It is not FDA-approved for any use and is classed as a research compound. WADA prohibits growth hormone-releasing factors, the category covering MOD-GRF (1-29), under S2.
Sermorelin is essentially the native, unmodified GHRH(1-29) fragment; it was FDA-approved for growth-hormone testing and pediatric growth failure at 30 µg/kg but was withdrawn from the market in 2008. MOD-GRF (1-29) carries four substitutions at positions 2, 8, 15 and 27 that block the DPP-4 cleavage native GHRH undergoes in plasma, stretching its bioactive half-life to about 30 minutes - the sermorelin dosing figures do not carry across to the modified peptide.