CJC-1295 is a 29-amino acid synthetic analogue of growth hormone-releasing hormone (GHRH), modified at four amino acid positions to resist enzymatic degradation and extend circulating half-life. The version without DAC (Drug Affinity Complex) — often called Mod GRF 1-29 — has a half-life of approximately 30 minutes; the DAC version binds albumin and extends this to 5–8 days, making it the longest-acting GHRH analogue with published human pharmacokinetic data.
CJC-1295 binds selectively to the GHRH receptor (GHRHR) on somatotroph cells in the anterior pituitary. GHRHR expression is largely restricted to the anterior pituitary, making CJC-1295 a more targeted probe for pituitary-driven GH signalling compared to ghrelin mimetics like ipamorelin, which have broader peripheral receptor distribution.
Upon binding, CJC-1295 induces conformational changes in GHRHR that activate heterotrimeric G-proteins, increasing intracellular cAMP and activating protein kinase A (PKA). This cascade enhances GH gene transcription and stimulates vesicle exocytosis, releasing GH pulses from somatotrophs into circulation.
The DAC modification extends half-life dramatically by adding a maleimidyl linker that binds covalently to cysteine-34 on circulating albumin — exploiting albumin's natural long circulating half-life to create a sustained-release depot. This produces prolonged GHRHR stimulation and maintained IGF-1 elevation for up to 28 days after repeated dosing.
CJC-1295 (GHRHR agonist) and ipamorelin (GHS-R1a agonist) act on entirely separate receptor populations in the pituitary. CJC-1295 increases cAMP via Gs protein, while ipamorelin activates phospholipase C via Gq protein — two distinct intracellular cascades converging on GH secretion.
Preclinical porcine data (Jørgensen et al., 2001) demonstrated that co-administration of GHRH and GHSR agonists produced GH responses 2–4× greater than either compound alone, providing the pharmacological rationale for dual-pathway protocols in GH axis research.
In the principal human PK/PD trial (2006, JCEM), single subcutaneous injections of CJC-1295 (with DAC) produced mean GH concentrations elevated 2–10 fold for 6+ days, and IGF-1 elevated 1.5–3 fold for 9–11 days. After multiple doses, IGF-1 remained above baseline for up to 28 days. Estimated half-life was 5.8–8.1 days. No serious adverse reactions were reported.
GH pulse amplitude versus placebo showed approximately 7.5-fold increase in treated subjects. Researchers also noted apparent increases in total pituitary GH mRNA, suggesting CJC-1295 may promote pituitary GH synthetic capacity beyond acute secretion.