CJC-1295: A Long-Acting GHRH Analog Built to Last

The short version

CJC-1295 is a synthetic version of the first 29 residues of growth hormone-releasing hormone, carrying four amino-acid changes that stabilize its shape and protect it from the enzyme (DPP-IV) that rapidly degrades natural GHRH. In its DAC form, a chemical linker on the C-terminus attaches covalently to circulating serum albumin — the most abundant protein in blood — and rides along with it for as long as albumin circulates, giving CJC-1295 DAC a measured half-life of roughly five to eight days ^[4].

In human studies, a single subcutaneous dose produced dose-dependent two- to ten-fold increases in mean GH for six days or more, and a 1.5- to three-fold rise in IGF-1 for nine to eleven days ^[4]. Pulsatile GH secretion — the natural rhythm the body uses to regulate the axis — was preserved even during this prolonged stimulation ^[5]. CJC-1295 is not approved for human use anywhere, it is banned in competitive sport, and this page lists no human dose.

What it is

CJC-1295 is a synthetic peptide built on hGRF(1-29) — the 29-amino-acid N-terminal fragment of human growth-hormone-releasing factor. Four substitutions distinguish it from the parent sequence: D-Ala at position 2, Gln at 8, Ala at 15, and Leu at 27. Together these lock the alpha-helix into a conformation that binds the GHRH receptor more effectively and resists enzymatic cleavage, deamidation and oxidation.

The DAC ('Drug Affinity Complex') variant adds a maleimidopropionyl (MPA) linker on a C-terminal lysine. That linker undergoes a Michael addition reaction with the free thiol on Cys34 of circulating serum albumin, forming a stable covalent conjugate that extends the peptide's plasma residence time toward that of albumin itself. The no-DAC form ('Modified GRF 1-29') keeps the four stabilizing substitutions but lacks the albumin-binding handle, making it a short-acting compound — pharmacokinetically very different, though the two are routinely conflated ^[7].

How it works

CJC-1295 binds the growth-hormone-releasing hormone receptor (GHRHR) on somatotroph cells in the anterior pituitary, activating the Gs/adenylyl cyclase/cAMP/PKA signaling cascade that stimulates both the synthesis and pulsatile release of growth hormone. The resulting rise in GH drives the liver to produce IGF-1, completing the somatotropic axis.

The DAC linker strategy was validated in a screen of hGRF(1-29) analogs bearing the maleimidopropionyl-lysine handle ^[7]. In rats, the lead compound — CJC-1295 — showed a four-fold increase in GH area-under-the-curve over two hours versus unconjugated hGRF(1-29), remained detectable in plasma beyond 72 hours, and was stable against DPP-IV cleavage in vitro ^[7]. A GHRH-knockout mouse study confirmed that once-daily dosing with CJC-1295 was sufficient to fully normalize body weight and length, while less frequent dosing was progressively less effective — a practical illustration of the receptor dynamics ^[6].

What the research shows

Human pharmacokinetics. The pivotal human PK study gave single subcutaneous doses of 30 or 60 micrograms per kilogram to healthy adults aged 21 to 61. Mean plasma GH rose two- to ten-fold and remained elevated for six or more days; IGF-1 rose 1.5- to three-fold and stayed above baseline for nine to eleven days. After multiple doses, IGF-1 remained elevated for up to 28 days. Estimated half-life: 5.8 to 8.1 days ^[4].

Preserved pulsatility. In healthy men aged 20 to 40, a single dose raised trough and basal GH approximately 7.5-fold and mean GH by about 46%, with IGF-1 rising about 45% one week later — but the frequency and magnitude of pulsatile GH bursts were statistically unchanged, indicating the natural GH rhythm persists under prolonged GHRH-analog stimulation ^[5].

Serum proteome shifts. In eleven healthy young men, CJC-1295 measurably altered the serum protein profile: apolipoprotein A1 and a transthyretin isoform decreased; an albumin fragment and immunoglobulin species increased; and the immunoglobulin/albumin-fragment signal correlated linearly with IGF-1, identifying candidate biomarkers of GH/IGF-1 axis activation ^[3].

Identification in anti-doping context. High-resolution LC-MS/MS definitively identified CJC-1295 as the active ingredient in an unmarked pharmaceutical preparation seized during anti-doping work — confirming both the detection methodology and the real-world supply ^[2].

Pharmacological class review. A 2025 Nature Reviews Endocrinology synthesis frames CJC-1295 within the broader GHRH-analog class, covering receptor signaling, analog design rationale, and the therapeutic and investigational landscapes for the entire compound family ^[1].

Reported effects, cautions and safety

The controversies surrounding CJC-1295 are well documented in the literature and deserve careful reading:

• Not approved; research-chemical status. CJC-1295 has no approved human indication anywhere. The original ConjuChem DAC program was discontinued; a patient death during that development era is frequently cited in connection with the halted Phase 2 trial, though no causal link to CJC-1295 was established in the public record ^[1].
• DAC vs. no-DAC conflation. CJC-1295 DAC (multi-day half-life) and Modified GRF 1-29 (the no-DAC, short-acting form) are pharmacokinetically very different compounds. Most online protocols treat them as interchangeable; the published literature does not ^[7].
• Sustained IGF-1 and theoretical cancer risk. Epidemiological work links higher IGF-1 to modestly increased risk of certain cancers (notably breast and prostate). GH-axis stimulation can also cause fluid retention, peripheral edema, and effects on insulin sensitivity ^[1].
• Regulatory and sport. FDA briefing materials for the 2024 Pharmacy Compounding Advisory Committee raised immunogenicity and safety concerns for GH secretagogues including CJC-1295; it is also prohibited at all times in sport under WADA Section S2, and detection assays are well established ^[2].
• Thin human evidence base. Published human data are limited to early pharmacokinetic studies; long-term efficacy and safety in humans are unestablished. Most community dosing protocols have no basis in controlled trial data ^[4][5].

Where it fits in GH-axis research

Among the three GHRH analogs on this desk, CJC-1295 occupies the extreme long-acting end of the durability spectrum — its albumin-tethering strategy is the most engineered, its half-life the longest, and its evidence base the most focused on pharmacokinetics rather than clinical outcomes ^[4]. Where Sermorelin is the natural-fragment story and Tesamorelin has approved human efficacy data, CJC-1295's record in humans is shorter and more recent. It is the compound that makes the GH-axis pulsatility question most interesting: can you stimulate the axis continuously without flattening the natural GH rhythm? The data suggest you can ^[5]. See how it lines up against the others on the comparison page.