CJC-1295 No DAC (GHRH analog) and ipamorelin (GHS-R1a agonist) stimulate endogenous GH through complementary cAMP and Ca²⁺ signaling pathways.
Clinical and mechanistic studies of GHRH+GHS-R1a agonists co-administration demonstrate amplified pulsatile GH release compared to either pathway alone, supporting dual-axis activation of the somatotroph system.
CJC-1295 without DAC is a synthetic analog of growth hormone–releasing hormone (GHRH amino acid 1–29 or Mod GHF1-29 ). This CJC-1295 is designed to stimulate endogenous growth hormone (GH) secretion through activation of the GHRH receptor (GHRH-R) on anterior pituitary somatotrophs.
Without the Drug Affinity Complex (DAC), it does not bind albumin, resulting in a shorter half-life and more physiologic, pulse-like GH stimulation.
Mechanistically, it activates the adenylyl cyclase–cAMP–protein kinase A (PKA) signaling cascade, promoting GH release and downstream increases in circulating insulin-like growth factor-1 (IGF-1) [1].
Because it works upstream at the hypothalamic–pituitary axis, CJC-1295 without DAC preserves endogenous inhibitory feedback regulation via somatostatin and IGF-1.
Ipamorelin is a selective growth hormone secretagogue (GHS) that binds to the ghrelin receptor (GHS-R1a) on anterior pituitary somatotrophs [2].
It stimulates endogenous GH release primarily through activation of the phospholipase C (PLC)–IP3–calcium signaling pathway, increasing intracellular calcium and promoting pulsatile GH secretion [3].
Unlike earlier GHS compounds and ghrelin itself, ipamorelin is relatively selective for GH release, with minimal stimulation of ACTH, cortisol, or hunger compared to less selective secretagogues [2].
By acting through a pathway distinct from GHRH analogs, ipamorelin is frequently studied in combination paradigms evaluating complementary stimulation of the somatotroph axis.
CJC-1295 without DAC and ipamorelin stimulate endogenous growth hormone (GH) release through distinct but convergent regulatory pathways within the HPA axis.
Their combined use is based on dual activation of GHRH and ghrelin receptor systems via:
Because these pathways operate independently, their combined activation should increase both the magnitude and efficiency of GH pulsatility.
Although published studies typically evaluate GHRH combined with GHRP compounds (such as GHRP-6 or ghrelin) rather than ipamorelin specifically, the mechanistic framework likely applies to ipamorelin due to its selective GHS-R1a agonism.
Cell-based studies demonstrate that co-activation of GHRH and GHS receptors can produce approximately twofold greater cAMP signaling compared to GHRH alone, suggesting receptor-level cross-talk and amplification of somatotroph responsiveness [4].
A clinical study evaluated whether ghrelin, the endogenous ligand for the GHS receptor, interacts synergistically with growth hormone–releasing hormone (GHRH) to stimulate GH secretion [5].
8 male adults were administered ghrelin (0.08, 0.2, and 1.0 μg/kg) intravenously alone or combined with 1.0 μg/kg GHRH. Results showed that combined administration with GHRH:
This study demonstrates that co-administration of ghrelin and GHRH produces true synergistic GH release in humans, exceeding additive stimulation from either agent alone.
The findings support the concept that dual activation of the GHRH receptor and GHS receptor enhances pituitary somatotroph responsiveness.
In some metabolic conditions (e.g., obesity-associated blunting of GHRH response), GHS agonists partially restored GH responsiveness [6].
Ipamorelin is highlighted in research contexts due to its relative selectivity for GH release, with minimal stimulation of ACTH and cortisol compared to earlier GHRP compounds.
This selective profile may allow more targeted evaluation of somatotroph activation without broader pituitary axis activation.
When paired with a short-acting GHRH analog such as CJC-1295 without DAC, the goal is typically to:
The absence of the DAC component in CJC-1295 results in a shorter half-life, aligning more closely with natural episodic GH dynamics rather than prolonged elevation.
Balanced ratios such as 2 mg + 2 mg or 5 mg + 5 mg can be conceptually described as targeting simultaneous engagement of:
Proportional dosing may theoretically promote coordinated receptor activation. However, precise optimization of dose ratios has not been definitively established in controlled combination trials and remains an empirical parameter in research settings.
References:
1 Sackmann-Sala, L., Ding, J., Frohman, L. A. and Kopchick, J. J. (2009) Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm. IGF Res., Elsevier BV 19, 471–477
2 Raun, K., Hansen, B. S., Johansen, N. L., Thøgersen, H., Madsen, K., Ankersen, M., et al. (1998) Ipamorelin, the first selective growth hormone secretagogue. Eur. J. Endocrinol., Oxford University Press (OUP) 139, 552–561
3 Mear, Y., Enjalbert, A. and Thirion, S. (2013) GHS-R1a constitutive activity and its physiological relevance. Front. Neurosci., Frontiers Media SA 7, 87
4 Cunha, S. R. and Mayo, K. E. (2002) Ghrelin and growth hormone (GH) secretagogues potentiate GH-releasing hormone (GHRH)-induced cyclic adenosine 3’,5'-monophosphate production in cells expressing transfected GHRH and GH secretagogue receptors. Endocrinology, The Endocrine Society 143, 4570–4582
5 Hataya, Y., Akamizu, T., Takaya, K., Kanamoto, N., Ariyasu, H., Saijo, M., et al. (2001) A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GH-releasing hormone in humans. J. Clin. Endocrinol. Metab., The Endocrine Society 86, 4552
6 Popovic, V., Damjanovic, S., Micic, D., Djurovic, M., Dieguez, C. and Casanueva, F. F. (1995) Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level. J. Clin. Endocrinol. Metab., The Endocrine Society 80, 942–947
Research Use Only. All findings described above are derived from preclinical studies (animal models and in vitro experiments). CJC-1295 (no DAC)+Ipamorelin (5+5) is not approved by the FDA for any diagnostic or therapeutic use in humans. Genesis Peptides makes no claims regarding human clinical efficacy. This product is sold exclusively for laboratory research.
Every lot undergoes six independent assays before release. Results are published in the lot-specific Certificate of Analysis.
Ipamorelin is a growth hormone secretagogue (GHS) from the peptidomimetic GHS family. In animal research, ipamorelin is described as a peripherally restricted ghrelin mimetic. The authors of that animal study suggested it may offer a novel approach for treating acute visceral and somatic pain. In a separate study, ipamorelin was one of the peptidomimetic GHS families from which the authors derived 4-fluorobenzoylated compounds for PET imaging of the ghrelin receptor.
In animal studies, ipamorelin is described as a peripherally restricted ghrelin mimetic and a selective ghrelin receptor agonist. In rats, ipamorelin was given intravenously to study visceral and somatic nociception. In animals, the anti-nociceptive effects of ipamorelin and HM01 were blocked by the ghrelin receptor antagonist H0900, indicating a ghrelin receptor-mediated mechanism. In the animal study, the authors suggest that this peripherally restricted ghrelin mimetic may offer a novel approach for treating acute visceral and somatic pain.
The provided facts do not mention FDA approval for ipamorelin. A review describes ipamorelin, a growth hormone axis secretagogue, as investigational, with uncertain safety profiles, product quality concerns, and widespread antidoping restrictions. The same review's conclusion calls peptides such as ipamorelin experimental substances with poorly defined long-term risks. Growth hormone releasing peptides, the class ipamorelin belongs to, are listed on the World Anti-Doping Agency Prohibited List.
A review describes Ipamorelin, a growth hormone axis secretagogue, as investigational, with an uncertain safety profile and product quality concerns. The same review concludes that peptides such as Ipamorelin remain experimental substances with poorly defined long-term risks, and that their use should be considered high-risk until longitudinal data are available. The review also notes that the largely unregulated supply chain for peptides such as Ipamorelin means products are often mislabeled or contaminated.
In a fish study, ipamorelin (IPA) at 5 or 30 µg significantly elevated serum luteinizing hormone (LH) and 11-ketotestosterone (11-KT) compared with controls. The available findings concern 11-ketotestosterone, so they do not directly show a rise in testosterone. Fish treated with 30 µg of IPA also showed a significant elevation in androgen receptor protein expression.
In ferrets, ipamorelin was given intraperitoneally at 1-3 mg/kg 30 s before cisplatin (5 mg/kg, i.p.), with subsequent doses every 24 h, and behaviour was recorded for up to 72 h. In these ferret experiments, intraperitoneally administered ipamorelin had no effect on cisplatin-induced acute or delayed emesis. Ipamorelin inhibited cisplatin-induced weight loss on the last day of the delayed phase (48-72 h) by approximately 24 % in ferrets. The authors concluded that intraperitoneally administered ipamorelin had beneficial effects in alleviating cisplatin-induced weight loss during the delayed phase in ferrets.
In rats with acetic acid-induced visceral hypersensitivity, ipamorelin significantly attenuated colonic hypersensitivity and somatic allodynia compared with vehicle controls. The anti-nociceptive effects of ipamorelin were blocked by the ghrelin receptor antagonist H0900, which indicates a ghrelin receptor-mediated mechanism in these rats. The authors describe ipamorelin as a peripherally restricted ghrelin mimetic and suggest it may offer a novel approach for treating acute visceral and somatic pain.
In a study in the tilapia Oreochromis mossambicus, Ipamorelin acetate (IPA), a ghrelin agonist, was given at 5 or 30 µg for 21 days. Both doses were reported to cause a significant, dose-dependent rise in food intake, along with significant increases in primary spermatocytes, secondary spermatocytes, and early spermatids compared with controls. Fish given 30 µg of IPA also showed a significant rise in late spermatids and in the areas of the lobule and lumen compared with the control group. The percentage of gonadotropin-releasing hormone (GnRH)-immunoreactive fibres in the hypothalamus and anterior pituitary gland did not differ significantly between groups.
The paper describes a method that detects Ipamorelin in urine by direct urine injection into a liquid chromatograph, followed by ion-mobility time-of-flight mass spectrometry. The authors describe this method as a facile, specific and sensitive assay for the peptidic compounds it covers, including Ipamorelin. In a human clinical trial, Ipamorelin (1-4) free acid was detected in urine samples after complete withdrawal of the parent substances. In human urine after nasal administration, Ipamorelin was metabolized intensively and excreted as a set of parent compounds with metabolites.
Gly-Ipamorelin is ipamorelin extended by an N-terminal glycine residue. Gly-Ipamorelin was identified as one of three analogues of growth hormone releasing peptides (GHRPs) found in black market products. The structure of Gly-Ipamorelin was characterised by high resolution (tandem) mass spectrometry, and its identity was additionally confirmed by custom synthesis.
FOR RESEARCH USE ONLY — Products are sold exclusively for in vitro and preclinical laboratory research. Not for human consumption or administration. Not intended for diagnostic or therapeutic use. These statements have not been evaluated by the FDA.