CJC-1295

CJC-1295 is a tetrasubstituted analog of growth-hormone-releasing hormone (GHRH 1-29) — the active fragment of native GHRH — engineered for resistance to enzymatic degradation and, in the DAC ("drug affinity complex") variant, for covalent binding to plasma albumin. The four amino-acid substitutions (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) protect against DPP-IV cleavage and proline isomerization; the DAC moiety — a maleimidopropionic acid linker on Lys³⁰ — covalently binds the cysteine-34 residue of circulating albumin, dramatically extending plasma half-life ([Teichman et al., *J Clin Endocrinol Metab* 2006, 91:799–805](https://doi.org/10.1210/jc.2005-1536)). Receptor mechanism is the same as Tesamorelin: GHRH-receptor agonism on pituitary somatotrophs, pulsatile GH release, hepatic IGF-1 production. The non-DAC form, often labeled "Modified GRF (1-29)" or "Mod GRF 1-29," shares the four substitutions but lacks the albumin tether and clears in roughly thirty minutes — a short pharmacological window suited to per-pulse dosing rather than tonic stimulation.

CJC-1295 is the GH-axis peptide whose pharmacokinetics most distinguish it from the rest of the class. The Phase I trial published by Teichman and colleagues in 2006 (*Journal of Clinical Endocrinology and Metabolism*) tested ascending single doses of CJC-1295 with DAC in healthy adults and reported plasma half-lives of 5.8 to 8.1 days, with single-dose GH elevations of 2- to 10-fold sustained for six days or longer and IGF-1 elevations of 1.5- to 3-fold lasting nine to eleven days. With repeated dosing, IGF-1 remained above baseline for up to 28 days. No serious adverse events were reported in the published trial, though the program subsequently encountered a serious safety event in a sponsor-driven hypertension subindication trial, which is part of why development under the original sponsor stalled. The most-cited practitioner application is the CJC-1295 + Ipamorelin stack: CJC-1295 with DAC provides a tonic GHRH-receptor stimulus, while Ipamorelin contributes a clean ghrelin-receptor pulse on top. The two molecules engage parallel pathways and produce a stronger combined GH response than either alone in animal pharmacology, though no large randomized trial has tested the stack in humans for the recomposition outcomes biohackers most care about. The non-DAC "Modified GRF (1-29)" variant is used by practitioners who prefer pulsatile dosing — typically synchronized with sleep onset — to avoid the chronic IGF-1 elevation the DAC variant produces. The choice between DAC and non-DAC is not cosmetic; the two pharmacological profiles carry different risk frames. The chronic GH and IGF-1 elevation produced by the DAC variant is the central safety question. Tonic IGF-1 elevation over weeks is a different risk profile than the pulsatile stimulation produced by Ipamorelin or short-acting GHRH analogs, and the human-safety database for sustained CJC-1295 + DAC use beyond Phase I is genuinely thin.