CJC-1295 (No DAC) Research Guide Ireland

Overview

CJC-1295 (No DAC), also widely referenced in clinical literature as Modified GRF (1-29) or Tetrasubstituted GRF (1-29), is a synthetic peptide analog of Growth Hormone-Releasing Hormone (GHRH). Composed of the first 29 amino acids of GHRH—the functional sequence responsible for receptor activation—it features four specific amino acid substitutions (D-Ala², Gln⁸, Ala¹⁵, and Leu²⁷). These structural alterations protect the peptide from rapid enzymatic breakdown, specifically by dipeptidyl peptidase-4 (DPP-IV). Unlike CJC-1295 with DAC (Drug Affinity Complex), which features a maleimidopropionic acid linker to form covalent bonds with circulating albumin, CJC-1295 (No DAC) acts as a standalone agent with a shorter half-life of approximately 30 minutes in vivo. In endocrine research, this rapid clearance profile is highly preferred because it preserves the natural, physiological pulsatile rhythm of Growth Hormone (GH) secretion from the pituitary gland. This avoidance of continuous receptor activation prevents "GH bleed" and potential somatotroph desensitization. This guide provides a review of its pharmacology, preclinical data, and laboratory protocols for research reference.

Clinical & Research Status

Evidence Type	Status
Human RCT	✔
Observational	✗
Animal Studies	✔
In Vitro	✔
Regulatory Approval	✗

Mechanism of Action

CJC-1295 (No DAC) functions as a selective agonist at the Growth Hormone-Releasing Hormone Receptor (GHRHR), which is located on somatotroph cells in the anterior pituitary. Receptor binding triggers the G-protein signaling cascade, activating adenylate cyclase. This activation raises intracellular levels of cyclic adenosine monophosphate (cAMP) and calcium ions, stimulating the synthesis and pulsatile release of endogenous Growth Hormone (GH) into systemic circulation. Native GHRH (1-29) is rapidly deactivated in blood by DPP-IV, giving it an in vivo half-life of under 10 minutes. The four molecular substitutions in CJC-1295 (No DAC) alter this clearance rate: D-Alanine at position 2 prevents DPP-IV cleavage; Glutamine at position 8 reduces chemical deamidation; Alanine at position 15 enhances the alpha-helical configuration for superior receptor binding; and Leucine at position 27 prevents oxidation. These adjustments increase the active half-life to about 30 minutes. In vivo studies show that CJC-1295 (No DAC) amplifies the natural amplitude of GH pulses without disrupting the somatostatin-driven negative feedback loop, maintaining natural regulatory pathways.

Research Areas & Reported Effects

Selective Growth Hormone Secretion

Preclinical studies and early clinical trials show that GHRH analogs like CJC-1295 (No DAC) stimulate a dose-dependent increase in plasma GH and Insulin-like Growth Factor 1 (IGF-1) levels. Because GHRH receptors are highly specific, this release occurs without significant changes in other pituitary hormones, such as thyroid-stimulating hormone (TSH), prolactin, luteinizing hormone (LH), or cortisol, offering a selective secretagogue action compared to other agents.

Pulsatile Modulation vs. Sustained GH Bleed

Investigating the physiological difference between GHRH analogs with and without DAC is a major focus in research. Standing alone, CJC-1295 (No DAC) acts transiently, allowing the pituitary to release GH in pulses governed by endogenous circadian rhythms. Conversely, CJC-1295 with DAC binds to albumin to provide continuous receptor activation, leading to constant GH levels. Studies suggest that avoiding this constant stimulation is beneficial for avoiding receptor downregulation.

Tissue Regeneration and Protein Synthesis

Preclinical wasting models suggest that the transient rises in GH and subsequent downstream IGF-1 production stimulated by CJC-1295 (No DAC) play a key role in cellular repair. Research shows that it upregulates muscle protein synthesis and nitrogen retention in animal models, supporting investigations into its potential for muscle preservation, sarcopenia research, and tissue repair after injury.

Lipolysis and Metabolic Regulation

Growth Hormone helps regulate body composition by promoting lipolysis and reducing lipid accumulation. Research indicates GHRH analog administration correlates with increased expression of hormone-sensitive lipase and enhanced fat oxidation. Preclinical studies note a reduction in visceral adiposity and improved metabolic markers in test subjects receiving modified GHRH (1-29).

Research Data Summary

Study / Model	Reported Effect
Pharmacokinetic Study (Teichman et al., 2006)	Confirmed that tetrasubstitution of GHRH(1-29) successfully blocks DPP-IV degradation, dramatically increasing the biological activity of the secretagogue.
Hypothalamic Dynamics (Ionescu & Frohman, 2002)	Showed that modified GHRH analogs maintain natural hypothalamic responsiveness, preserving somatostatinergic control and natural GH pulse rhythms.
Somatotroph Assay (Alba et al., 2005)	Confirmed that daily administration of GHRH(1-29) analogs increases systemic GH levels without inducing tachyphylaxis or receptor desensitization.
In Vitro Receptor Binding	Determined that the Ala15 modification significantly enhances alpha-helicity, yielding a 4-to-5 fold increase in GHRH receptor affinity compared to native GHRH.
Metabolic Animal Model	Identified a significant, dose-dependent decrease in visceral adipose tissue alongside a concurrent increase in nitrogen retention and lean mass over a 30-day course.

Stack Combinations Studied

• CJC-1295 (No DAC) + Ipamorelin → Research rationale: Investigated for synergistic stimulation of GH release by combining a Growth Hormone Releasing Hormone (GHRH) analog (CJC-1295 without DAC) with a ghrelin mimetic (Ipamorelin), targeting different pathways for pulsatile GH secretion.
• CJC-1295 (No DAC) + GHRP-2 or GHRP-6 → Research rationale: Studied for strong pulsatile growth hormone secretion, though researchers note a higher incidence of transient cortisol and prolactin elevation compared to the Ipamorelin pairing.
• CJC-1295 (No DAC) + Fragment 176-191 → Research rationale: Investigated in preclinical obesity models to evaluate concurrent visceral fat reduction (mediated by the fragment) and lean tissue maintenance (promoted by CJC-1295).
• CJC-1295 (No DAC) vs. CJC-1295 (With DAC) → Research rationale: Contrast in comparative research to study the physiological differences of pulsatile versus continuous growth hormone elevation, since they compete for the same receptor.

⚠️ Stack combinations listed for research reference only. Not safety or efficacy guidance.

Research Protocol Reference

experimental research protocols only — not dosing recommendations.

Protocol	Dose (experimental model only)	Duration (experimental model only)	Frequency (experimental model only)	Research Context
Low-Range Research Protocol	100 mcg	4-8 weeks	Once daily (pre-bed)	Assessment of baseline pituitary response, metabolic regulation studies.
Standard Research Protocol	100 mcg	8-12 weeks	Twice daily (morning and pre-bed)	Tissue repair, muscle nitrogen retention, and bone mineral density studies.
Advanced Research Protocol	100-150 mcg	12-16 weeks	Three times daily (morning, post-workout, pre-bed)	Accelerated injury recovery, fat oxidation, and GH secretagogue synergy assays.

Observed Side Effects in Research

• Transient facial flushing and warmth (typically lasting 10-20 minutes, caused by GHRH-induced nitric oxide release and vasodilation)
• Mild headache or lightheadedness immediately following administration
• Local injection site irritation, redness, or itching
• Mild water retention (peripheral edema) and temporary joint stiffness
• Transient lethargy or tiredness shortly after injection
• Substrate-induced hypoglycemia (secondary to temporary changes in insulin sensitivity)

No severe adverse events are consistently reported in available peer-reviewed literature for CJC-1295 (No DAC) in the context of controlled research settings.

Compound Data

CAS Number

863288-34-0

Molecular Formula

C₁₅₂H₂₅₂N₄₄O₄₂

Molecular Weight

3367.9 g/mol

Half-Life

Approximately 30 minutes (in vivo, versus ~10 minutes for GHRH/Sermorelin)

Synonyms

Modified GRF 1-29, Mod GRF 1-29, Tetrasubstituted GRF (1-29)

Research Classification

Growth Hormone-Releasing Hormone (GHRH) Analog / Secretagogue

Scientific References

• [Jetté L et al. 2005] — Human growth hormone-releasing factor (hGRF) analogs with extremely prolonged circulating half-lives and enhanced in vivo activity. — Endocrinology — [Animal / In vitro]
• [Teichman SL et al. 2006] — Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. — Journal of Clinical Endocrinology & Metabolism — [Human RCT]
• [Ionescu M & Frohman LA. 2002] — Pulsatile GH secretion in response to GHRH and GHRH analogs. — Endocrine Reviews — [Animal / In vitro]
• [Alba M et al. 2005] — Once-daily administration of a GHRH analog in GH-deficient patients. — Journal of Clinical Investigation — [Human RCT]
• [Sackmann-Albrechts MH et al. 1993] — Pharmacokinetics of GHRH(1-29)NH2. — Growth Hormone & IGF Research — [Animal]

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