# CJC-1295: A Research Digest on the GHRH Analog — With-DAC, No-DAC, and the Ipamorelin Stack

> CJC-1295, a 29-amino-acid GHRH analog, elevated plasma GH 2- to 10-fold for six or more days in healthy adults at a single subcutaneous dose. This site documents the peer-reviewed record on both forms and the ipamorelin stack.

## What the CJC-1295 Literature Has Demonstrated

CJC-1295 is a synthetic 29-amino-acid analog of human growth hormone-releasing hormone (GHRH). A single subcutaneous injection of the with-DAC form elevated mean plasma GH concentrations 2- to 10-fold in healthy adults and sustained that elevation for six days or more; IGF-1 rose 1.5- to 3-fold for nine to eleven days [1]. That finding — one injection, nearly two weeks of measurable hormonal response — is the result of a maleimide–Cys34 thioether bond that tethers the peptide to circulating albumin after injection, extending half-life from roughly thirty minutes (no-DAC form) to 5.8–8.1 days (with-DAC) [3].

The two forms share a 29-residue GHRH backbone with four amino-acid substitutions that confer resistance to dipeptidyl peptidase-IV (DPP-IV) cleavage. The with-DAC form carries an additional C-terminal Drug Affinity Complex (DAC) extension — the structural difference that produces a 250-fold difference in half-life and fundamentally distinct dosing architectures. Understanding this distinction is the starting point for reading the CJC-1295 literature [14].

The human evidence base is modest: two randomized, placebo-controlled, double-blind trials conducted by Teichman et al. (2006) and Ionescu and Frohman (2006) in a combined n=24 healthy adults, with a maximum duration of 49 days [1, 2]. No peer-reviewed human pharmacokinetic data exists for the no-DAC form (Mod GRF 1-29). Rodent studies extend the picture — GHRH-knockout mice normalized body weight, bone length, and GH mRNA expression with once-daily CJC-1295 over five weeks [4] — but species translation is not established.

## What the Research Says: CJC-1295 Benefits

The downstream findings across the CJC-1295 literature cluster around two axes: GH/IGF-1 elevation and the downstream physiology that follows from it.

In the Teichman 2006 trial, mean GH rose 2- to 10-fold dose-dependently at doses of 30, 60, 90, and 125 μg/kg SC; IGF-1 followed, rising 1.5- to 3-fold and remaining elevated for nine to eleven days [1]. The Ionescu and Frohman 2006 sub-study confirmed that pulsatile GH secretion is preserved during continuous CJC-1295 administration — trough GH rose 7.5-fold above baseline (P<0.0001) and mean GH rose 46%, but pulse frequency and amplitude remained intact [2].

For body composition, the most rigorous human evidence in the GHRH analog class comes from tesamorelin, an FDA-approved GHRH analog. In randomized controlled trials, tesamorelin reduced visceral adipose tissue by 10.9% at six months and approximately 18% at twelve months in HIV-associated lipodystrophy [9]; a 2026 meta-analysis of GHRH analog RCTs confirmed the class effect [21]. CJC-1295 and tesamorelin are distinct compounds; the tesamorelin data is cited here as mechanistic context for the GHRH compound class, not as direct CJC-1295 evidence.

Ipamorelin counteracted glucocorticoid-induced decreases in bone formation in rats — periosteal bone formation rate was four times higher in the ipamorelin group [10] — and counteracted prednisolone-induced catabolism in a seven-day rat model, improving whole-body nitrogen balance comparably to exogenous GH [11].

## What Is CJC-1295? (Peptide, Not Steroid)

CJC-1295 is a peptide — a short chain of amino acids — not a steroid. It has no steroidal ring structure and does not directly bind androgen, estrogen, or glucocorticoid receptors. It acts exclusively on pituitary somatotroph GHRH receptors (GHRH-R) via a Gαs-coupled adenylyl cyclase cascade that elevates intracellular cAMP, activates protein kinase A (PKA), and drives both GH exocytosis and GH gene transcription [12].

CJC-1295 is not FDA-approved for any indication. It was reviewed by the FDA Pharmacy Compounding Advisory Committee in December 2024 for potential 503A bulk-drug compounding inclusion (docket FDA-2024-N-4777); the FDA identified potential immunogenicity concerns [16]. Its WADA status is prohibited under Section S2.

## What Does CJC-1295 Do?

CJC-1295 is a synthetic GHRH analog that binds pituitary somatotroph GHRH receptors, stimulating pulsatile or sustained growth hormone secretion depending on whether the DAC extension is present. The GHRH-R activation cascade — Gαs coupling → adenylyl cyclase → cAMP elevation → PKA → CREB phosphorylation → GH gene transcription, plus voltage-dependent calcium-channel opening for acute GH exocytosis — is comprehensively reviewed in a 2025 paper by Halmos et al. [12].

Downstream, elevated GH drives hepatic IGF-1 synthesis. GH also stimulates sodium reabsorption in the distal nephron [8], explaining the water retention reported at higher doses [13].

## References

[1] Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295. J Clin Endocrinol Metab. 2006;91(3):799-805. https://pubmed.ncbi.nlm.nih.gov/16352683/
[2] Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295. J Clin Endocrinol Metab. 2006;91(12):4792-7. https://pubmed.ncbi.nlm.nih.gov/17018654/
[3] Jetté L, et al. hGRF1-29-albumin bioconjugates: identification of CJC-1295. Endocrinology. 2005;146(7):3052-8. https://pubmed.ncbi.nlm.nih.gov/15817669/
[4] Alba M, et al. Once-daily CJC-1295 normalizes growth in GHRH knockout mice. Am J Physiol Endocrinol Metab. 2006;291(6):E1290-4. https://pubmed.ncbi.nlm.nih.gov/16822960/
[8] Johannsson G, et al. GH increases extracellular volume via distal nephron sodium reabsorption. J Clin Endocrinol Metab. 2002;87(4):1743-9. https://pubmed.ncbi.nlm.nih.gov/11932310/
[9] Falutz J, et al. Effects of tesamorelin in HIV-infected patients. J Acquir Immune Defic Syndr. 2010;53(3):311-22. https://pubmed.ncbi.nlm.nih.gov/20101189/
[10] Andersen NB, et al. Ipamorelin counteracts GC-induced bone loss in rats. Growth Horm IGF Res. 2001;11(5):266-72. https://pubmed.ncbi.nlm.nih.gov/11735244/
[11] Aagaard NK, et al. GH and GH secretagogue effects on nitrogen balance in steroid-treated rats. Growth Horm IGF Res. 2009;19(5):426-31. https://pubmed.ncbi.nlm.nih.gov/19231263/
[12] Halmos G, et al. GHRH-R and its signaling. Rev Endocr Metab Disord. 2025. https://pubmed.ncbi.nlm.nih.gov/39934495/
[13] Teichman SL, et al. [Adverse events.] J Clin Endocrinol Metab. 2006;91(3):799-805. https://pubmed.ncbi.nlm.nih.gov/16352683/
[14] Jetté L, et al. [DAC/no-DAC structural data.] Endocrinology. 2005;146(7):3052-8. https://pubmed.ncbi.nlm.nih.gov/15817669/
[16] U.S. FDA PCAC. Bulk drug substances for 503A — December 2024. FDA Docket FDA-2024-N-4777. https://www.fda.gov/media/183819/download
[21] Various authors. Body composition outcomes of Tesamorelin: A meta-analysis. ScienceDirect (in press 2026). https://pubmed.ncbi.nlm.nih.gov/41545261/

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A letterpress monograph on the GHRH analog CJC-1295 — with-DAC and without, hand-set from the peer-reviewed record, no clinic, no counter.