CJC-1295 No DAC

1) Clinical Overview

CJC-1295 (No DAC), often called Mod GRF (1-29), is a short-acting, tetra-substituted analogue of growth-hormone-releasing hormone (GHRH) that retains the first 29 amino acids of native GHRH and lacks the albumin-binding Drug Affinity Complex (DAC). The most common form is [D-Ala², Gln⁸, Ala¹⁵, Leu²⁷]-GHRH(1-29)-NH₂, a substitution pattern widely reported in anti-doping analytical work and reference materials. It binds the pituitary GHRH receptor to stimulate pulsatile GH release and, secondarily, raises circulating IGF-1. Compared with unmodified fragments (e.g., sermorelin), the four substitutions were engineered to improve peptide stability (e.g., resistance to DPP-IV cleavage at the N-terminus and mitigation of Asn⁸ lability), while maintaining short-acting physiology. 

2) Human Clinical Findings

Direct, peer-reviewed human trials labeled specifically as “CJC-1295 without DAC” are not available. However, closely related GHRH(1-29) analogues with one or more of the same stabilizing substitutions have been studied in humans:

D-Ala²-GHRH(1-29)-NH₂ (infusion study in healthy men): In a crossover trial, adding D-Ala² significantly reduced metabolic clearance and prolonged disappearance half-time vs native GHRH(1-29) (t½ ≈ 6.7 ± 0.5 min vs 4.3 ± 1.4 min), helping explain the analogue’s higher biological activity in vivo. 

[Nle²⁷]-GHRH(1-29)-NH₂ (5-month RCT in older adults): Nightly subcutaneous dosing (10 μg/kg) acutely triggered ~2 hours of GH release after each injection and increased nocturnal GH output; IGF-1 and IGFBP-3 rose within two weeks. Skin thickness increased in both sexes, and men showed gains in lean mass and insulin sensitivity. The only adverse effect noted was transient hyperlipidemia that resolved by study end. 

GHRH(1-29) (6-week study in older men): Nightly 2 mg injections increased mean nocturnal GH, GH peak amplitude and area under the GH peaks; two of six strength measures improved. No significant adverse effects were observed. Authors concluded multiple daily doses are more effective than single nightly doses for IGF-1-mediated outcomes—consistent with the short-acting profile of non-DAC analogues. 

For context, the long-acting DAC-bearing version (CJC-1295 with DAC) prolonged half-life to days and lifted IGF-1 in adults while preserving physiologic GH pulsatility—illustrating how “No DAC” is intended for shorter, more physiologic pulses rather than sustained exposure.

3) Mechanism & Effects

CJC-1295 (No DAC) activates the GHRH receptor on somatotrophs, increasing cAMP/PKA signaling and exocytosis of GH in a pulse-like manner. Short-acting GHRH analogues augment the amplitude/duration of nocturnal GH peaks without increasing pulse frequency, aligning with physiologic secretion patterns seen during sleep. These effects typically translate into downstream IGF-1 increases when dosing frequency and timing are sufficient. 

Chemically, the tetra-substitution helps the peptide withstand key degradation routes: D-Ala² can blunt N-terminal dipeptidyl peptidase attack; Gln⁸ reduces Asn-specific deamidation at position 8; Ala¹⁵ can improve potency; and Leu²⁷ avoids methionine oxidation—together yielding a somewhat longer-lasting yet still brief GH secretagogue compared with unmodified sermorelin. 

4) Safety & Considerations

Across human studies with short-acting GHRH(1-29) analogues, reported adverse effects were generally mild. In a 5-month randomized, placebo-controlled trial of [Nle²⁷]-GHRH(1-29)-NH₂, the only reported adverse effect was transient hyperlipidemia; vitals and glycemia were unchanged, and lean mass improved in men. In a 6-week nightly GHRH study, no significant adverse effects were observed. As with any agent that raises GH/IGF-1, theoretical risks include edema, arthralgias, insulin resistance, or unmasking of latent neoplasia, so long-term safety for non-approved indications remains insufficiently characterized. 

Regulatory notes. CJC-1295 and other GHRH analogues are prohibited in sport under WADA’s S2 category. By contrast, sermorelin (unmodified GHRH(1-29)) was formerly FDA-approved in the U.S. and later discontinued for commercial reasons; FDA determined it was not withdrawn for safety or effectiveness. 

References 

1. Teichman SL, et al. J Clin Endocrinol Metab. 2006;91:799–805. (CJC-1295 with DAC: PK/PD, IGF-1 increases, preserved pulsatility).
2. Soule S, King JA, Millar RP. J Clin Endocrinol Metab. 1994;79:1208–1211. (D-Ala²-GHRH(1-29) increases t½ and reduces clearance in men). 
3. Khorram O, Laughlin GA, Yen SS. J Clin Endocrinol Metab. 1997;82:1472–1479. ([Nle²⁷]-GHRH(1-29) RCT in older adults; GH/IGF-1, LBM, safety). 
4. Vittone J, et al. Metabolism. 1997;46:89–96. (Nightly GHRH in older men; GH dynamics, strength, safety). 
5. Frohman LA, et al. J Clin Invest. 1986;78:906–913. (Rapid inactivation of GHRH by plasma DPP-IV; mechanistic basis for stabilization). 
6. Campbell RM, et al. Peptides. 1994;15(1):129–136. (Design rationale for stabilizing substitutions at positions 2, 8, 15, 27). 
7. Ishida J, et al. Bioorg Med Chem Lett. 2020;30:127079. (Review noting sermorelin’s ~11–12 min half-life). 
8. WADA. The 2025 Prohibited List. (Lists GHRH analogues including CJC-1295). 
9. U.S. FDA (Federal Register, 2013). Determination that GEREF (sermorelin) was not withdrawn for safety or effectiveness.