CJC-1295, DAC CJC 1295, or CJC-1295 DAC, is a synthetic growth hormone releasing hormone (GHRH) peptide analog with a thiol-reactive group attached, comprising a “drug affinity complex” (DAC). Compared to GHRH, fifteen of forty-four amino acids in the chain are removed; a lysine molecule, to which the reactive group is affixed, is added. In circulation, the nature of the added group allows the DAC to resist kidney excretion and peptidase enzymatic breakdown, primarily by binding to albumin. As a result, compared to natural or non-DAC growth hormone secretagogue peptides, DAC CJC-1295 circulates for a much longer period with slower breakdown and excretion.
CJC-1295 mimics GHRH, the hypothalamic peptide signaling hormone that increases the amplitude of growth hormone (GH) release from “active” somatotrophs, pituitary cells that produce, store, and release GH (active when somatostatin is not inhibiting release of GH). 44-amino-acid GHRH is particularly fragile and acts on the pituitary for a short window, which does not ensure potency of GH release. Ghrelin, another peptide signaling hormone, plays the role of somatostatin antagonist, allowing GHRH to take effect on more somatotrophs; ghrelin (and its analogs GHRP-2, GHRP-6, ipamorelin, hexarelin, etc) and GHRH (or its analogs, such as Modified GRF 1-29 and CJC-1295) are synergistic, releasing much more GH from the pituitary when they happen to coincide physiologically.
Physiologically ghrelin and GHRH are both released in specific life patterns such as post-exercise, during slow-wave sleep (SWS), or to release GH for developmental purposes; as age increases, physiological GH release from the pituitary decreases, but pituitary production and storage of GH typically remains high. Although exogenous rHGH (181-amino-acid) has been studied to address the effects of “somatopause” in aging, secretagogue peptides such as CJC-1295 could allow for release of endogenous GH that rivals youthful production or exogenous administration of growth hormone, without many of the secondary side-effects and expense of the synthetic variety.
In healthy men, one week after a single dose of CJC-1295, trough levels of GH were up seven-fold relative to control, with pulsatility of endogenous GH pulses unaffected, leading the authors to conclude “Long-acting GHRH preparations may have clinical utility in patients with intact pituitary GH secretory capability.”:
GH pulsatility was assessed by 20-min blood sampling during an overnight 12-h period in healthy 20- to 40-yr-old men before and 1 wk after injection of either 60 or 90 microg/kg...GH secretion was increased after CJC-1295 administration with preserved pulsatility. The frequency and magnitude of GH secretory pulses were unaltered. However, basal (trough) GH levels were markedly increased (7.5-fold) and contributed to an overall increase in GH secretion (mean GH levels, 46%) and IGF-I levels (45%)...CJC-1295 increased trough and mean GH secretion and IGF-I production with preserved GH pulsatility. The marked enhancement of trough GH levels by continuous GHRH stimulation implicates the importance of this effect on increasing IGF-I. 
Compared to exogenous rHGH, the preservation of endogenous pulses of GH observed with CJC-1295 means it may be a better choice where pituitary function is intact.
Ionescu M, Frohman LA. Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long- Acting GH-Releasing Hormone Analog. The Journal of Clinical Endocrinology & Metabolism. 2006 91(12):4792-4797
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Gautam D, et al. Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth. Proceedings of the National Academy of Sciences of the United States of America. Vol. 106, No. 15 (Apr. 14, 2009), pp. 6398-6403
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