CJC-1295 DAC vs CJC-1295.

CJC-1295 with DAC (also written DAC:GRF, CJC-1295 DAC) is a synthetic, long-acting analog of growth hormone-releasing hormone (GHRH). It is built on the bioactive N-terminal GHRH(1-29) fragment with several amino-acid substitutions, plus a "Drug Affinity Complex" (DAC): a maleimidopropionyl group that lets the peptide bind covalently to circulating albumin after injection. It was developed in the mid-2000s by ConjuChem Biotechnologies as an investigational drug; it is not an approved medicine and today circulates mainly as a research/gray-market peptide.

CJC-1295 is a synthetic analog of growth hormone-releasing hormone (GHRH), based on the first 29 amino acids of human GHRH (GRF 1-29) with several amino-acid substitutions that resist enzymatic degradation. The name is used for two distinct molecules: "CJC-1295 with DAC," which carries a Drug Affinity Complex (a maleimidoproprionic acid linker) that covalently binds to circulating albumin to dramatically prolong its action; and "CJC-1295 without DAC" (often sold as "modified GRF 1-29" or "Mod GRF 1-29"), which lacks the albumin-binding linker. It was originally developed by the Canadian biotech company ConjuChem as an investigational therapeutic.

Like native GHRH, CJC-1295 binds the GHRH receptor on anterior pituitary somatotrophs and stimulates synthesis and pulsatile release of growth hormone (GH), which in turn drives hepatic and peripheral IGF-1 production. Two engineering features extend its action: amino-acid substitutions in the GHRH(1-29) backbone resist cleavage by dipeptidyl-peptidase-4 (DPP-4), and the DAC maleimide group forms a covalent bond with cysteine-34 of serum albumin, shielding the peptide from renal filtration and proteolysis so it persists in plasma for days rather than minutes. Because it amplifies the body's own GH axis rather than supplying exogenous GH, secretion remains somewhat pulsatile and subject to negative feedback (e.g., somatostatin).

As a GHRH analog, CJC-1295 binds the GHRH receptor on somatotroph cells of the anterior pituitary, activating Gs-protein/cAMP/PKA signaling to stimulate synthesis and pulsatile release of endogenous growth hormone (GH), which in turn raises hepatic insulin-like growth factor 1 (IGF-1). The four substitutions in the GRF(1-29) backbone (notably at the position-2 alanine that is the dipeptidyl peptidase-IV cleavage site) protect the peptide from rapid breakdown, extending the half-life of the non-DAC form to roughly 30 minutes versus minutes for native GHRH. In the DAC version, the maleimide linker forms a covalent bond with cysteine-34 of serum albumin, creating a long-circulating depot; because it raises GH in a more sustained rather than sharply pulsatile manner, it is described as increasing trough and mean GH while largely preserving the body's own pulse pattern.

Human evidence comes mainly from early-phase ConjuChem trials in healthy adults. Teichman et al. (JCEM, 2006) reported that single subcutaneous doses produced dose-dependent, sustained elevations of GH and IGF-1, with IGF-1 remaining above baseline for several days and repeated weekly/biweekly dosing maintaining elevated IGF-1. Ionescu and Frohman (JCEM, 2006) showed that despite continuous GHRH-receptor stimulation, GH secretion remained pulsatile in healthy men. Preclinical support includes Alba et al. (Am J Physiol Endocrinol Metab, 2006), where once-daily CJC-1295 normalized growth in GHRH-knockout mice, and Sackmann-Sala et al. (Growth Horm IGF Res, 2009), which characterized GH/IGF-1-axis-driven serum protein changes. Crucially, there are no published controlled trials demonstrating clinical outcomes (body composition, strength, fat loss, anti-aging, or healing) in humans; the human data establish a pharmacodynamic GH/IGF-1 effect, not proven therapeutic benefit, and the program was discontinued without an approved indication.

The principal human evidence is a single 2006 Phase 1 study in healthy adults by Teichman et al. (J Clin Endocrinol Metab, PMID 16352683), which reported that one subcutaneous dose of CJC-1295 with DAC produced dose-dependent increases in mean plasma GH of roughly 2- to 10-fold for 6 days or more and IGF-1 increases of about 1.5- to 3-fold for 9-11 days, with an estimated half-life of 5.8-8.1 days and IGF-1 staying above baseline up to 28 days after repeated dosing. ConjuChem advanced the DAC compound into a Phase 2 trial in HIV-associated visceral obesity (ClinicalTrials.gov NCT00267527), but that 12-week trial was terminated in 2006. Beyond these, robust controlled human efficacy and long-term safety data are essentially absent; there are no large or long-term trials, no published outcomes for the non-DAC "modified GRF 1-29" form in humans, and much of the mechanistic rationale rests on GHRH-class pharmacology rather than direct trials of this molecule. Claims about body composition, recovery, or anti-aging benefit are not supported by published controlled human outcome data.

In the short early-phase human studies, the most consistently noted effects were injection-site reactions and transient flushing; sustained IGF-1 elevation also raises theoretical concerns common to GH-axis stimulation, such as fluid retention, joint discomfort, carpal-tunnel-type symptoms, and reduced insulin sensitivity. Long-term human safety is essentially uncharacterized: no large or long-duration controlled trials were completed, and chronically elevated GH/IGF-1 is a biologically plausible (though unproven for this compound) concern for promoting growth of existing neoplasms. Real-world risk is compounded by the fact that material sold as "CJC-1295 DAC" is unregulated and may vary in purity, identity, or sterility. No dosing or administration guidance is provided here.

In the short Phase 1 work, CJC-1295 with DAC was described as generally well tolerated, with the kinds of effects expected from GHRH-class agents (e.g., injection-site reactions, flushing, headache); however, this reflects small numbers and short follow-up. The Phase 2 HIV trial (NCT00267527) was terminated in 2006, and a participant death during the program drew scrutiny, though available reporting attributed that death to pre-existing coronary disease rather than establishing causation by the drug; the episode underscores how thin the safety record is. Sustained elevation of GH/IGF-1 carries class-level theoretical concerns familiar from growth-hormone pharmacology, including fluid retention, joint/muscle pain, insulin resistance and elevated blood glucose, and a theoretical concern about promoting growth of existing malignancy; long-term safety in humans is simply unknown. Much material sold as "CJC-1295" online is from unregulated sources with no purity, sterility, or identity guarantees, adding contamination and mislabeling risks.

CJC-1295 (with or without DAC) is not approved by the FDA or any major regulator for any use; clinical development was discontinued and it is treated as an unapproved/investigational substance, with U.S. authorities also flagging it as unsuitable for pharmacy compounding. It is prohibited in sport at all times by the World Anti-Doping Agency as a GH-releasing factor under Category S2 of the Prohibited List.

CJC-1295 (with or without DAC) has never been approved by the FDA or any major regulatory agency for any indication and remains an investigational compound that did not complete clinical development. It is not an approved medicine; it is sold only as a "research chemical," and GHRH analogs/GH secretagogues of this type are prohibited in sport by the World Anti-Doping Agency.