CJC-1295 (No DAC) + Ipamorelin

What CJC-1295 (No DAC) + Ipamorelin is

CJC-1295 (No DAC)—also widely called Modified GRF(1-29) or Mod GRF 1-29—is a 29-amino-acid synthetic analogue of endogenous GHRH, the hypothalamic hormone that instructs the pituitary gland to manufacture and release growth hormone ^[1]. Unlike the longer-acting 'DAC' formulation that covalently binds to serum albumin via a drug-affinity complex linker, the No DAC version lacks this modification entirely, giving it a plasma half-life of approximately 30 minutes and producing an acute, pulsatile GH response that closely mirrors the body's natural secretory pattern ^[2]. Four strategically placed amino-acid substitutions at positions 2, 8, 15, and 27 of the native GHRH(1-29) sequence protect the peptide from rapid degradation by the enzyme dipeptidyl peptidase-4 (DPP-4), substantially extending its functional half-life compared to unmodified GHRH(1-29) without altering its pulsatile pharmacokinetic profile ^[3].

Ipamorelin (research designation NNC 26-0161) is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) developed by Novo Nordisk in the late 1990s from a medicinal chemistry program aimed at identifying growth hormone secretagogues with an improved selectivity profile over earlier compounds in the class ^[4]. First described in the peer-reviewed literature in 1998, it was characterized as 'the first selective growth hormone secretagogue'—a pentapeptide that releases GH via the same ghrelin/GHS-R1a receptor as the endogenous hunger hormone ghrelin, but without the significant cortisol, ACTH, or prolactin elevation seen with earlier GH-releasing peptides such as GHRP-6 ^[5]. When co-studied with CJC-1295 (No DAC), the two compounds engage separate but complementary receptor pathways—the GHRH receptor (GHRHR) and the ghrelin receptor (GHS-R1a) respectively—creating a dual-mechanism framework for studying pulsatile GH axis modulation ^[6].

What it is being researched for

1. Dual-pathway GH axis stimulation and pulsatility research

The central scientific rationale for studying CJC-1295 (No DAC) and Ipamorelin together is the concept of dual-pathway synergy at the anterior pituitary. CJC-1295 (No DAC) binds and activates the GHRH receptor (GHRHR) on somatotroph cells, stimulating GH synthesis and release, while Ipamorelin independently activates the ghrelin receptor (GHS-R1a), which signals through a distinct second-messenger cascade ^[6]. Research using GHRH and GHRP compounds has demonstrated that simultaneous activation of both receptor systems produces a synergistic—not merely additive—GH response, consistent with the well-established concept that GHRH and ghrelin/GHRP signals converge on the secretory machinery of somatotrophs to amplify GH burst amplitude ^[7]. The No DAC formulation is specifically preferred in combination research because its short half-life allows investigators to study acute, pulsatile GH dynamics rather than the sustained basal elevation produced by the DAC variant, enabling cleaner characterization of combined receptor-pathway kinetics ^[2].

2. IGF-1 axis signalling and downstream anabolic pathways

Growth hormone released from the pituitary in response to GHRH-analogue and GHS stimulation drives the liver to produce insulin-like growth factor 1 (IGF-1), which is the primary downstream mediator of many GH-dependent anabolic and metabolic effects. Human pharmacological data with CJC-1295 (the DAC form) demonstrated dose-dependent increases in mean plasma IGF-1 concentrations of 1.5- to 3-fold above baseline lasting 9–11 days after a single injection in healthy adults, providing a benchmark for how robustly GHRH-analogue stimulation can engage this axis ^[8]. For Ipamorelin, IGF-1 levels are observed to rise following repeated administration in a dose-dependent manner, though published preclinical data indicate they typically remain within the upper physiological range rather than reaching supraphysiological levels associated with exogenous GH injection ^[9]. The combination of both peptides in experimental models is proposed to contribute to anabolic processes including positive nitrogen balance and lean body mass preservation through this coordinated IGF-1 pathway activation ^[6].

3. Bone metabolism and longitudinal bone growth

The GH/IGF-1 axis is a major regulator of bone metabolism, and both peptides in this combination have been studied individually in this context. Ipamorelin was shown to dose-dependently increase longitudinal bone growth rate (LGR) in adult female rats over a 15-day study period, as measured by intravital tetracycline labelling in the proximal tibia metaphysis ^[10]. A separate rodent study by Svensson and colleagues published in the Journal of Endocrinology (2000) showed that Ipamorelin and GHRP-6 both increased bone mineral content in adult female rats, suggesting GHS-mediated GH release can influence skeletal anabolism ^[9]. These findings are preclinical in nature; no published human trials have evaluated the bone-specific effects of Ipamorelin or the CJC-1295 (No DAC) + Ipamorelin combination, representing a significant gap in the translational evidence base ^[9].

4. Gastrointestinal motility and postoperative recovery

Ipamorelin has been investigated as a ghrelin mimetic in the context of gastrointestinal motility, given that the GHS-R1a receptor is expressed not only in the pituitary but also in enteric and vagal neurons that regulate gut function. A rodent study of postoperative ileus (POI) found that Ipamorelin, as a selective GH secretagogue and ghrelin receptor agonist, accelerated gastrointestinal transit and ameliorated symptoms in a surgically induced ileus model, with repetitive treatment improving cumulative fecal pellet output, food intake, and body weight recovery compared to vehicle ^[11]. A Phase II randomized, double-blind, placebo-controlled human trial of Ipamorelin for POI following abdominal surgery enrolled over 100 patients and evaluated time to first bowel movement and length of hospital stay; however, this trial did not meet its primary endpoint ^[9]. This remains the only published randomized controlled trial of Ipamorelin in humans to date.

5. Selectivity profiling and hormonal safety research

One of the most studied pharmacological properties of Ipamorelin is its hormonal selectivity relative to earlier growth hormone-releasing peptides. The landmark 1998 characterization by Raun and colleagues demonstrated that Ipamorelin did not release ACTH or cortisol at levels significantly different from baseline, even at concentrations more than 200-fold above the ED₅₀ for GH release—a selectivity profile that earlier GHRPs such as GHRP-6 and GHRP-2 did not achieve ^[5]. This makes Ipamorelin a useful research tool for isolating GH/IGF-1 pathway effects from the confounding hormonal changes seen with less selective secretagogues, and explains why it is the preferred GHRP in combination frameworks with GHRH analogues like CJC-1295 (No DAC) ^[4]. The No DAC formulation of CJC-1295 similarly permits researchers to study selective GHRHR stimulation in an acute-pulse context, without the prolonged, tonic receptor activation that complicates interpretation with the DAC variant ^[2].

6. Neuroendocrine axis modelling and circadian GH research

CJC-1295 (No DAC) is specifically valued in laboratory research for its ability to replicate physiological pulsatile GH secretion patterns rather than producing continuous, tonic GH elevation. Its short half-life (~30 minutes) and absence of albumin binding make it suitable for studying somatotroph activation, GH pulse frequency and amplitude, and circadian or ultradian GH rhythm dynamics in preclinical models ^[2]. The combination with Ipamorelin is proposed to study sequential activation kinetics—research reports suggest Ipamorelin's GHS-R1a-mediated activity has an earlier onset profile that may prime GH release, while CJC-1295 extends the duration of GH-related axis activity, together producing a response profile more closely resembling the natural amplitude and duration of endogenous GH secretory bursts ^[6]. Veldhuis and Bowers (2009) established in a controlled human study that simultaneous GHRH and GHRP infusion produces marked, time-dependent GH release, underscoring the mechanistic value of this dual-pathway approach in human neuroendocrinology research ^[7].

How it is thought to work

CJC-1295 (No DAC) binds to and activates the GHRH receptor (GHRHR) on somatotroph cells of the anterior pituitary. This receptor is a G-protein-coupled receptor (GPCR) that, upon activation, signals through the adenylate cyclase/cyclic AMP (cAMP) second-messenger pathway, ultimately stimulating GH gene expression and triggering the release of stored GH in discrete pulses ^[3]. Four amino-acid substitutions in the tetrasubstituted sequence protect CJC-1295 (No DAC) from rapid cleavage by DPP-4, extending its effective plasma half-life to approximately 30 minutes compared to the 7–10 minute half-life of native GHRH(1-29), while preserving the pulsatile pharmacokinetic profile that mirrors physiological GHRH activity ^[3]. The absence of the drug-affinity complex (DAC) modification means the peptide does not bind albumin and is cleared relatively quickly, making it well-suited for research models requiring controllable, episodic GH stimulation rather than prolonged axis activation ^[2].

Ipamorelin works through an entirely separate but complementary mechanism: it binds to the ghrelin receptor (GHS-R1a) on pituitary somatotrophs, the same receptor activated by the endogenous hunger and GH-releasing hormone ghrelin ^[4]. GHS-R1a signalling operates through the phospholipase C/inositol trisphosphate (PLC/IP₃) pathway, mobilizing intracellular calcium and stimulating GH secretion independently of the cAMP cascade engaged by GHRHR ^[7]. Critically, ghrelin-receptor agonists such as Ipamorelin are also thought to partially suppress hypothalamic somatostatin (SS) release; since somatostatin is the primary endogenous inhibitor of GH secretion, reducing somatostatin tone while simultaneously stimulating two GH-releasing receptor pathways creates the mechanistic basis for the supraadditive GH response observed when GHRH analogues and GHRPs are co-administered ^[7]. This convergence on pituitary somatotrophs via two distinct second-messenger systems is the foundational rationale for studying CJC-1295 (No DAC) and Ipamorelin together ^[6].

Where the evidence stands

The strongest published human pharmacological data for this combination's component compounds comes from the 2006 randomized, double-blind, placebo-controlled ascending-dose trials by Teichman and colleagues in the Journal of Clinical Endocrinology and Metabolism. These trials used CJC-1295 with DAC (not the No DAC form) in healthy adults aged 21–61 years and demonstrated dose-dependent increases in mean plasma GH concentrations of 2- to 10-fold above baseline lasting 6 or more days, and mean plasma IGF-1 concentrations of 1.5- to 3-fold above baseline lasting 9–11 days after a single injection, with evidence of a cumulative effect after multiple doses ^[8]. For Ipamorelin specifically, the foundational selectivity pharmacology was established in animal models (swine and rats) by Raun and colleagues (1998), showing robust GH release without ACTH or cortisol elevation even at doses more than 200-fold above the GH ED₅₀ ^[5]. Johansen and colleagues (1999) demonstrated dose-dependent longitudinal bone growth stimulation in adult female rats over 15 days of Ipamorelin treatment ^[10]. The only completed human RCT of Ipamorelin—a Phase II trial in postoperative ileus—did not meet its primary endpoint, and no published human RCTs have evaluated the specific CJC-1295 (No DAC) + Ipamorelin combination ^[9].

Several important limitations define this evidence landscape. First, the key human GH/IGF-1 data was generated with CJC-1295 DAC, a pharmacokinetically distinct compound from CJC-1295 No DAC; the no-DAC form has not been evaluated in published human clinical trials of comparable scope ^[2]. Second, neither CJC-1295 (No DAC) nor Ipamorelin has completed Phase 3 clinical trials for any GH-related indication ^[9]. Third, all body-composition, bone density, lean mass, and recovery-related research for Ipamorelin remains preclinical—there are no completed human trials examining these endpoints for Ipamorelin alone or in combination with any GHRH analogue ^[9]. The mechanistic rationale for synergy between GHRH-pathway and GHS-R1a-pathway compounds is well-supported by human neuroendocrine research (Veldhuis and Bowers, 2009), but this has not been translated into efficacy trials of the specific CJC-1295 (No DAC) + Ipamorelin pairing in humans ^[7]. Researchers should interpret preclinical findings cautiously and recognise that human translation remains an open question.

Frequently asked questions

What is the difference between CJC-1295 with DAC and CJC-1295 without DAC?

CJC-1295 with DAC contains a maleimidopropionyl linker that covalently binds the peptide to circulating serum albumin, extending its plasma half-life to approximately 6–8 days and producing sustained, tonic GH and IGF-1 elevation. CJC-1295 without DAC (also called Mod GRF 1-29) lacks this linker entirely, has a half-life of approximately 30 minutes, and produces a brief, acute GH pulse that closely resembles the body's natural pulsatile secretory pattern. They are not interchangeable research tools and produce fundamentally different pharmacokinetic and GH-release profiles.

Why are CJC-1295 (No DAC) and Ipamorelin often studied together?

The two peptides activate entirely separate receptor systems: CJC-1295 (No DAC) stimulates the GHRH receptor (GHRHR), while Ipamorelin stimulates the ghrelin receptor (GHS-R1a). These two pathways signal through distinct intracellular cascades that converge on pituitary somatotrophs, and research demonstrates that co-activation of both pathways produces a synergistic GH response greater than either compound achieves alone. Combining a GHRH-pathway amplifier with a GHS-R1a-pathway inducer is therefore studied as a dual-mechanism approach to modelling robust, physiologically patterned GH secretion.

Is Ipamorelin the same as GHRP-6 or other growth hormone-releasing peptides?

No. While Ipamorelin belongs to the same growth hormone secretagogue class and binds the same GHS-R1a receptor as GHRP-6, GHRP-2, and Hexarelin, it was characterized in 1998 as 'the first selective growth hormone secretagogue' because it does not significantly elevate cortisol, ACTH, or prolactin even at very high concentrations. Earlier GHRPs were found to stimulate these additional hormones, which complicates experimental interpretation. This selectivity profile is Ipamorelin's primary pharmacological distinction in the research literature.

Has the CJC-1295 (No DAC) + Ipamorelin combination been tested in human clinical trials?

As of late 2026, no published human randomized controlled trials have evaluated the specific CJC-1295 (No DAC) + Ipamorelin combination for any indication. Human pharmacology data for CJC-1295 relates to the DAC formulation, not the No DAC form. The only published human RCT involving Ipamorelin alone—a Phase II trial in postoperative ileus—did not meet its primary endpoint. The combination remains in the preclinical and mechanistic research stage.

What does 'pulsatile GH release' mean and why does it matter in research?

Pulsatile GH release refers to the natural pattern in which the pituitary gland secretes growth hormone in discrete bursts rather than at a constant rate. This pulsatility is physiologically important because many downstream effects of GH—including IGF-1 production, protein synthesis, and metabolic regulation—are sensitive to the amplitude and frequency of these pulses, not just average GH levels. CJC-1295 (No DAC) is preferred over the DAC formulation in certain research models specifically because its short half-life preserves this pulsatile pattern rather than producing continuous GH stimulation.

What is IGF-1 and how does it relate to CJC-1295 and Ipamorelin research?

IGF-1 (insulin-like growth factor 1) is a hormone produced primarily by the liver in response to GH stimulation, and it mediates many of the anabolic, metabolic, and skeletal effects associated with GH activity. In CJC-1295 human pharmacology studies, IGF-1 elevation serves as the primary measurable downstream biomarker of GH axis activation, with published data showing 1.5- to 3-fold increases lasting 9–11 days after a single injection of the DAC formulation. IGF-1 levels are also monitored in Ipamorelin preclinical studies as an indicator of effective GHS-R1a-mediated GH secretion.

What are the known safety signals from CJC-1295 research?

The 2006 Phase I trials of CJC-1295 with DAC in healthy adults reported that subcutaneous administration was generally safe and relatively well tolerated, particularly at lower doses. Reported adverse events were typical of GHRH-analogue class effects. It is important to note that the clinical development program for CJC-1295 (with DAC) was halted following a patient death in a Phase II study, and the compound never received regulatory approval for therapeutic use. The No DAC formulation has not been independently evaluated in comparable human safety trials.

Can CJC-1295 (No DAC) + Ipamorelin be purchased legally in Canada for research?

In Canada, peptides including CJC-1295 (No DAC) and Ipamorelin are sold by licensed research-peptide suppliers for in vitro and preclinical laboratory research purposes only. They are not approved drugs under Health Canada's Food and Drugs Act and may not be sold or used as human therapeutics without regulatory approval. Researchers should verify current regulatory status and ensure all use conforms to applicable institutional and federal guidelines.

Does Ipamorelin raise cortisol or affect other hormones?

Based on preclinical pharmacology data, Ipamorelin is distinguished from earlier growth hormone-releasing peptides by its lack of significant cortisol or ACTH elevation, even at concentrations more than 200 times above the level required for maximal GH release. Unlike ghrelin itself, Ipamorelin also does not significantly stimulate appetite at typical research concentrations. This selectivity profile makes it a cleaner research tool for isolating GH/IGF-1 axis effects, though all findings are based on animal models and the single failed human RCT.

How does somatostatin relate to the mechanism of this combination?

Somatostatin, also called growth hormone-inhibiting hormone (GHIH), is released from the hypothalamus and acts as the primary brake on GH secretion. GHRH and ghrelin/GHS-R agonists both stimulate GH release, but ghrelin-mimetic compounds like Ipamorelin are also thought to partially suppress hypothalamic somatostatin release, effectively reducing the inhibitory tone on the pituitary. This dual action—stimulating two GH-releasing receptor pathways while simultaneously reducing somatostatin tone—is proposed as one mechanism behind the supraadditive GH response observed when GHRH analogues and GHRPs are combined in research models.

Glossary

GHRH (Growth Hormone-Releasing Hormone)

A 44-amino-acid hypothalamic peptide that stimulates the anterior pituitary to synthesize and secrete growth hormone by binding to the GHRH receptor (GHRHR) on somatotroph cells.

GHS-R1a (Growth Hormone Secretagogue Receptor 1a)

The G-protein-coupled receptor activated by ghrelin and synthetic ghrelin mimetics such as Ipamorelin, which triggers GH release through a distinct intracellular pathway from the GHRH receptor.

Somatotroph

A specialized cell type in the anterior pituitary gland that synthesizes and secretes growth hormone in response to stimulation from GHRH and ghrelin-pathway signals.

IGF-1 (Insulin-Like Growth Factor 1)

A peptide hormone produced primarily by the liver in response to GH stimulation, which mediates the anabolic, metabolic, and skeletal growth-promoting effects downstream of GH secretion.

Somatostatin

A hypothalamic inhibitory peptide that suppresses GH release from the pituitary and acts as the primary counterbalance to the stimulatory signals of GHRH and ghrelin-pathway compounds.

DPP-4 (Dipeptidyl Peptidase-4)

A circulating enzyme that rapidly degrades native GHRH(1-29) and other peptides containing certain N-terminal sequences; the amino-acid substitutions in CJC-1295 (No DAC) are specifically designed to confer resistance to DPP-4 cleavage.

DAC (Drug Affinity Complex)

A maleimidopropionyl chemical linker added to CJC-1295 (the DAC formulation) that covalently binds the peptide to serum albumin after injection, extending its plasma half-life from ~30 minutes to approximately 6–8 days; the No DAC form lacks this modification entirely.

Growth Hormone Secretagogue (GHS)

A class of synthetic or natural compounds that stimulate GH release from the pituitary, typically by acting on the GHS-R1a receptor; Ipamorelin is a member of this class and was the first characterized as selective for GH without significant cortisol or ACTH stimulation.

References

1. Modified GRF (1-29) — Wikipedia — Wikipedia / encyclopedic summary of primary literature
2. CJC-1295 — Wikipedia — Wikipedia / encyclopedic summary of primary literature
3. CJC-1295 No DAC (Mod GRF 1-29): Research Overview — NeuroPept Labs — Supplier research reference page
4. Ipamorelin — Wikipedia — Wikipedia / encyclopedic summary of primary literature
5. Ipamorelin, the first selective growth hormone secretagogue — Raun K et al., European Journal of Endocrinology, 1998 — PubMed / European Journal of Endocrinology (PMID 9849822)
6. Pharmacological and Metabolic Insights into the Ipamorelin & CJC-1295 Blend — Biotech Peptides — Biotech Peptides research blog
7. Determinants of GH-releasing hormone and GH-releasing peptide synergy in men — Veldhuis JD, Bowers CY, American Journal of Physiology-Endocrinology and Metabolism, 2009 — American Journal of Physiology – Endocrinology and Metabolism (PubMed: 19240251)
8. 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 adults — Teichman SL et al., Journal of Clinical Endocrinology and Metabolism, 2006 — PubMed / Journal of Clinical Endocrinology and Metabolism (PMID 16822944)
9. Ipamorelin: Mechanism, Research, and Status — Superpower — Superpower.com research guide (aggregates primary literature)
10. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats — Johansen PB et al., Growth Hormone & IGF Research, 1999 — PubMed / Growth Hormone & IGF Research (PMID 10373343)
11. Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus — ScienceDirect — ScienceDirect / peer-reviewed journal article