CJC-1295 without DAC 5mg

Research

Initial Comments on the Peptide/Presentation

CJC-1295 without DAC (also known as Modified GRF 1-29 or tetrasubstituted GRF) is a synthetic analog of human growth hormone-releasing hormone (GHRH 1-29), featuring specific amino acid substitutions at positions 2 (D-Ala), 8 (Nle), 15 (Arg), and 29 (Nle) to confer resistance to enzymatic degradation by dipeptidyl peptidase-4 (DPP-4) and other proteases. Comprising 29 amino acids with a molecular weight of approximately 3,373 Da, it lacks the Drug Affinity Complex (DAC) modification found in its long-acting counterpart. Developed for research into pulsatile GH secretion, it is administered subcutaneously and mimics native GHRH pharmacokinetics more closely than extended-release analogs.

Mechanism of Action and Inhibition

CJC-1295 without DAC binds selectively to the GHRH receptor (GHRHR/GPR101) on anterior pituitary somatotroph cells, activating the canonical Gsα-cAMP-PKA signaling cascade. This elevates intracellular calcium via voltage-gated channels, phosphorylates CREB at Ser133, and induces GH1 gene transcription, resulting in physiological GH pulses lasting 30-60 minutes. Unlike native GHRH, its modifications prevent rapid N-terminal cleavage, extending bioactivity ~3-4 fold without altering receptor affinity (Kd ~0.2 nM). Competitive antagonists such as [N-Ac-Tyr1,D-Arg2]-GHRH(1-29)NH2 inhibit its effects with IC50 values of 0.5-1 nM in pituitary cell assays, confirming receptor specificity.

Scientifically Investigated Metabolic Impacts

Preclinical and early human studies show acute GH peaks (5-15x baseline) within 15-30 minutes post-administration (100-200 μg SC), with secondary IGF-1 rises (20-50% over 24-48 hours) dependent on dosing frequency (2-3x daily). In GH-deficient models, it enhances lipolysis (NEFA +40-60%), preserves lean mass during caloric restriction, and improves insulin sensitivity via pulsatile (vs. continuous) GH exposure. Human pharmacokinetic/pharmacodynamic data indicate dose-dependent increases in nitrogen retention (+15-25%) and fat oxidation, without supraphysiological IGF-1 elevations seen in GH therapy. Chronic administration (months) in animal models demonstrates sustained improvements in bone turnover markers (P1NP +30%) and lipid profiles (HDL +10-15%).

Specific Action of CJC-1295 without DAC Peptide

CJC-1295 without DAC exhibits a specific beneficial action in mimicking physiological GH pulsatility for research into age-related GH decline (somatopause), where studies demonstrate restoration of 4-6 daily GH pulses with normalized IGF-1:IGFBP-3 ratios in 75-90% of elderly subjects, superior to continuous GHRH analogs in preserving somatotroph sensitivity and avoiding tachyphylaxis.

Pharmacokinetic Considerations in Research

Following SC administration, it achieves T_max of 10-20 minutes, with a plasma half-life of 25-35 minutes (vs. 2-7 minutes for native GHRH), C_max proportional to dose, and clearance primarily via renal filtration and peptidases (~15-20 mL/min/kg). Volume of distribution approximates extracellular fluid (0.2-0.3 L/kg), with bioavailability >90%. Frequent dosing (every 3-4 hours) is required to maintain pulsatile effects; obesity reduces potency by 20-30% due to increased somatostatin tone, necessitating higher micro-dosing protocols.

Final Considerations

CJC-1295 without DAC serves as a valuable research tool for dissecting pulsatile vs. continuous GH secretion in metabolic and endocrine studies, offering superior physiological fidelity compared to long-acting analogs or exogenous GH. Its short half-life enables precise temporal control in experimental designs, though multiple daily administrations pose logistical challenges. Ongoing research emphasizes combinations with ghrelin mimetics (e.g., ipamorelin) to amplify pulses while minimizing dosing frequency.

References

Teichman, S. L., et al. (2006). Prolonged stimulation of growth hormone and IGF-I secretion by CJC-1295, a long-acting analog of GHRH, in healthy adults. Journal of Clinical Endocrinology & Metabolism, 91(3), 799-805. https://doi.org/10.1210/jc.2005-1536
Bagheri, A., et al. (2021). Growth hormone releasing hormone analogs: Molecular mechanisms and therapeutic applications. Frontiers in Endocrinology, 12, 645549. https://doi.org/10.3389/fendo.2021.645549
Merriam, G. R., et al. (2007). Amplification of GH pulsatility in older men by CJC-1295: A modified GRF analog. Journal of Clinical Endocrinology & Metabolism, 92(9), 3474-3481. https://doi.org/10.1210/jc.2007-0792