CJC-1295

Origin and Structure

CJC-1295 — in its original, DAC-free form — is a synthetic analogue of the first 29 residues of human growth hormone releasing hormone (GHRH), which carry essentially all of GHRH's receptor-binding activity. The molecule is also known in the literature and in research-chemical catalogs as Modified GRF 1-29, Mod GRF 1-29, and sometimes CJC-1295 without DAC to distinguish it from the long-acting CJC-1295 DAC variant.

Four amino-acid substitutions differentiate Modified GRF 1-29 from native GHRH(1-29): D-Ala at position 2 (blocking DPP-4 cleavage), Gln at position 8, Ala at position 15, and Leu at position 27. The result is a peptide with a half-life of roughly 30 minutes — long enough to be clinically practical, but short enough that each dose produces a discrete, pulsatile GH release rather than a sustained plateau.

Why "No DAC" Is the Feature, Not the Limitation

The pulsatile pharmacokinetic profile is the central design intent of CJC-1295 without DAC. Native GH secretion is itself pulsatile — the pituitary releases GH in discrete bursts, most prominently during slow-wave sleep — and that pulse pattern appears important for downstream IGF-1 signalling and for avoiding the receptor-desensitization that sustained exposure can cause. Mod GRF 1-29 preserves this pulse-based biology, which is why it is the form typically preferred in research protocols aiming to mimic physiologic GHRH tone rather than to flood the pituitary with continuous signal. The long-acting DAC variant takes the opposite approach and is discussed separately on our CJC-1295 DAC page.

Mechanism and the Ipamorelin Synergy

CJC-1295 activates the GHRH receptor on pituitary somatotrophs, driving both GH synthesis and pulsatile release through the Gs/cAMP/PKA cascade. This is a mechanistically distinct pathway from the one used by ipamorelin and other growth hormone releasing peptides (GHRPs), which act at the ghrelin receptor (GHSR-1a) on the same cells. Because the two pathways converge on GH release through independent intracellular signalling, combining a GHRH analogue with a GHRP produces synergistic rather than additive GH output — a well-characterized pharmacologic effect first demonstrated in the 1980s with earlier GHRH and GHRP tools and routinely replicated with modern analogues.

The pulsatile profile of Mod GRF 1-29 makes it the more natural GHRH partner for pulsatile GHRP dosing. A typical research protocol pairs the two into simultaneous injections, timed to empty-stomach windows, so that the combined GH pulse is not blunted by postprandial insulin and amino-acid elevations. Our stack explainer covers the protocol logic in more depth.

Clinical Development

ConjuChem Biotechnologies — the Canadian company that originated the CJC-1295 platform in the early 2000s — advanced the long-acting DAC variant into clinical trials and discontinued the program after Phase 2 in 2007 following a reported cardiac safety signal. The short-acting Modified GRF 1-29 was never the focus of a registrational program and has no completed Phase 3 data. Most of what is known about its human pharmacokinetics comes from small pharmacology studies and from the broader sermorelin literature — sermorelin is the original GHRH(1-29) analogue from which Mod GRF's structural logic is derived.

Practical Considerations

Research protocols typically use 100 mcg per injection, dosed one to three times daily via subcutaneous injection, usually in combination with ipamorelin at matched doses. Dosing is timed to fasted windows — before breakfast, before training, and before bed — to avoid blunting of the GH pulse by elevated insulin or amino-acid levels. Course lengths in anecdotal protocols typically run 8–12 weeks with scheduled breaks.

Safety and Regulatory Status

Modified GRF 1-29 is not FDA-approved and has no formal regulatory indication anywhere. It is listed on the World Anti-Doping Agency prohibited list at all times under class S2 (peptide hormones, growth factors, related substances). Commonly reported side effects at research doses are mild and transient: injection-site reactions, transient facial flushing (a histamine-release effect), mild headache, and water retention. Active malignancy is a contraindication — as for any GH-axis stimulant — because IGF-1 signalling can support proliferation of some tumor types.

Supply is almost entirely through research-chemical vendors and compounding pharmacies; product identity and purity vary considerably. For the long-acting albumin-bound counterpart, see CJC-1295 DAC; for the FDA-approved GHRH analogue in the same family, see tesamorelin.