CJC-1295 Without DAC: Research Overview

CJC-1295 without DAC — also called Modified GRF(1-29) or Mod GRF 1-29 — is a 29-amino-acid analogue of endogenous growth hormone-releasing hormone (GHRH). Unlike the DAC version of CJC-1295, this peptide contains no Drug Affinity Complex, meaning it does not bind to albumin and retains a pharmacokinetic profile very close to native GHRH. It is studied exclusively in research settings and is not approved by any regulatory agency for human therapeutic use.

What is CJC-1295 Without DAC?

CJC-1295 without DAC is derived from the first 29 amino acids of human GHRH, with four amino-acid substitutions at positions 2, 8, 15, and 27 that confer greater resistance to dipeptidyl peptidase IV (DPP-IV) cleavage compared with the native peptide. These substitutions extend its in-vitro stability while preserving its core receptor-binding profile. The peptide binds the GHRH receptor on pituitary somatotroph cells, triggering release of growth hormone (GH).

The critical distinction from CJC-1295 with DAC is the absence of the maleimidoproprionic acid (MPA) group that enables covalent binding to serum albumin. In the DAC version, albumin binding dramatically extends circulating half-life to roughly 5.8–8.1 days. Without DAC, half-life returns to approximately 30 minutes, producing short, pulse-like GH elevations rather than sustained, blunted release.

Mechanism of Action

After subcutaneous injection, CJC-1295 without DAC diffuses into circulation and binds the pituitary GHRH receptor, a G-protein-coupled receptor (GPCR) that activates adenylyl cyclase, raises intracellular cAMP, and triggers somatotroph GH secretion. Because the peptide is rapidly cleared by peptidases — particularly DPP-IV — within 20–30 minutes, the resulting GH pulse mirrors the amplitude and duration of a natural endogenous GH pulse.

This pulsatility is regarded in the research literature as physiologically meaningful: natural GH secretion is episodic, with large nocturnal pulses interspersed by low baseline levels. Continuous or sustained elevation of GHRH signalling — as occurs with the DAC formulation — blunts GH pulse amplitude over time. Research combining CJC-1295 without DAC with a GHRP such as ipamorelin leverages synergistic action on both the GHRH receptor and the ghrelin receptor, amplifying pulsatile GH output.

What the Research Shows

The foundational pharmacokinetic characterisation of CJC-1295 (with DAC) was published by Teichman et al. in 2006, which simultaneously provides the comparative baseline for understanding the unmodified, no-DAC form. That randomised, placebo-controlled, dose-escalation study in healthy adults documented that the albumin-binding DAC modification produced a mean terminal half-life of 5.8–8.1 days versus the ~30-minute half-life of the unmodified parent peptide. The Teichman study also demonstrated that GH mean concentrations increased 2- to 10-fold and IGF-1 levels rose 1.5- to 3-fold over 28 days of weekly CJC-1295 (DAC) administration.

A complementary study by Ionescu and Frohman (2006) in the American Journal of Physiology examined once-daily administration of a long-acting GHRH analogue — structurally related to the Mod GRF 1-29 scaffold — in a GHRH-knockout mouse model, confirming that periodic GHRH pulses are sufficient to normalise growth, whereas continuous infusion is not. This mechanistic finding underpins the research interest in short-acting GHRH analogues as tools for investigating pulsatile GH physiology.

A subsequent human study (PMID 17018654) using CJC-1295 with DAC confirmed that pulsatile GH secretion persists even under GHRH analogue administration, supporting the hypothesis that the GHRH receptor retains some capacity for episodic gating. For researchers wishing to preserve maximal pulsatility, the no-DAC form is therefore the standard research tool.

Pharmacokinetics

CJC-1295 without DAC has an approximate plasma half-life of 30 minutes following subcutaneous injection in humans. Peak GH secretion occurs roughly 15–30 minutes post-injection, with GH levels returning to near-baseline within 2–3 hours. This profile contrasts markedly with CJC-1295 with DAC, whose albumin conjugation yields a half-life of approximately 5.8–8.1 days. The no-DAC form is eliminated primarily by proteolytic degradation, with DPP-IV as the principal enzyme, followed by endopeptidase cleavage. Renal clearance of intact peptide is minimal.

Because of its rapid clearance, CJC-1295 without DAC requires frequent dosing in research protocols — typically multiple injections per day — to maintain an elevated mean GH secretory pattern. This stands in direct contrast to the once-weekly or twice-weekly administration used in DAC-based research protocols.

Common Research Dose Ranges

Not medical advice. These are ranges reported in research literature, not personalized recommendations. Consult your physician.

Published and pre-clinical research literature has used subcutaneous doses ranging from 100 mcg to 300 mcg per injection, administered two to three times daily in human and animal studies. Some protocols combine CJC-1295 without DAC with a GHRP (growth hormone-releasing peptide) such as ipamorelin at equivalent or lower doses in order to amplify pulsatile GH response. Dose frequency is higher than with the DAC form due to the short half-life.

Storage and Handling

CJC-1295 without DAC is typically supplied as a lyophilised (freeze-dried) powder for research use. Lyophilised vials should be stored at 2–8°C (refrigerated) and protected from light. Reconstitution is performed with bacteriostatic water; once reconstituted, the solution is generally stable for 2–4 weeks when refrigerated and should not be frozen. Reconstituted solutions should be inspected for particulate matter or discolouration before use; affected vials should be discarded.

What It Is NOT

CJC-1295 without DAC is frequently confused with several related compounds. It is not CJC-1295 with DAC — despite sharing a name prefix, the two have fundamentally different half-lives and injection frequencies. It is not sermorelin, which is the unmodified 29-amino-acid GHRH(1-29) peptide without the four protective substitutions; sermorelin has an even shorter half-life (~10–12 minutes) and was previously FDA-approved as Geref. It is not GHRH itself (the 44-amino-acid native peptide). It is not a GHRP or ghrelin mimetic such as ipamorelin or GHRP-6, which act on an entirely different receptor (the ghrelin/GHS-R1a receptor). It is also not growth hormone (somatropin) itself.

References

Key citations for this overview are listed below. The Teichman 2006 study (PMID 16352683) is the primary human pharmacokinetic reference. See also the companion Pepticker guide on CJC-1295 with DAC for the contrasting pharmacology of the albumin-binding formulation.