CJC-1295 with DAC vs modified GRF(1–29)

CJC-1295 with DAC was designed to bind albumin and prolong growth-hormone signaling, and early studies measured its persistence and hormone effects in healthy volunteers. Modified GRF(1–29) shares the modified GHRH core but lacks that extension; most selected reports concern chemical identification, leaving much less human pharmacology to compare.

Research reviewed 2026-10-14. Educational information only.

The shared core and the albumin-binding addition

The name CJC-1295 has been used for more than one material. This comparison uses CJC-1295 with DAC for the albumin-binding development molecule and modified GRF(1–29) for the four-substitution, amidated 29-residue fragment without that extension. GRF means growth hormone-releasing factor, another name for growth hormone-releasing hormone, GHRH. Both names belong to a family built around the signal that stimulates pituitary growth-hormone release.

The shared modified core has D-alanine at position 2, glutamine at position 8, alanine at position 15 and leucine at position 27. CJC-1295 with DAC adds a modified lysine carrying a reactive maleimidopropionamide group at the C terminus. DAC means drug affinity complex. The addition permits covalent association with albumin, an abundant circulating protein. Jetté and colleagues’ 2005 development paper connects this chemistry to experiments in rat pituitary cells and rats.

FDA’s material-by-material assessment evaluates peptides with and without DAC separately, including their salt forms. “Acetate” identifies the ion paired with the peptide in a salt; it does not tell us whether DAC is present. A glycine-extended preparation introduces another distinction: Gajda and colleagues identified an additional N-terminal glycine in seized modified-GRF-related material. A preparation with this extra residue is a different molecule, so a result for the unextended fragment does not establish its activity.

The main differences

What is the chemical distinction?

Both peptides are based on growth hormone-releasing hormone (GHRH), which signals the pituitary to release growth hormone. DAC is an added chemical group that allows CJC-1295 to attach to albumin, an abundant blood protein. Modified GRF(1–29) lacks this addition.

How long did the peptide remain in human blood?

A human elimination half-life requires blood samples collected after administration of a defined peptide. It describes how long the measured concentration takes to fall by half during the elimination phase; it does not measure recovery from injury or another clinical benefit.

What human hormone response was measured?

Growth hormone (GH) is released in pulses. Between pulses its concentration falls to a trough. GH also promotes production of insulin-like growth factor 1 (IGF-1), so the peptide concentration, GH pattern and IGF-1 response are related but different measurements.

What do the identification and detection papers contribute?

Chemical identification studies test what a preparation contains. Laboratory detection studies can also add known peptides to urine to check whether an assay detects them. Neither design shows what happens after a person receives the peptide.

Is a clinical benefit or safety advantage established?

A change in hormone concentrations does not by itself establish better strength, body composition, injury recovery or long-term health. Those benefits, and any safety difference between the peptides, require trials that measure them directly.

Why an exposure change can alter endocrine physiology

GHRH stimulates receptors on growth-hormone-producing cells in the anterior pituitary. GH then influences other tissues and promotes production of insulin-like growth factor 1, IGF-1, in the liver and elsewhere. The system includes pulses, hormone stores and feedback. A persistent releasing-hormone signal can therefore have several observable consequences: peptide remains in blood, GH secretion changes, and IGF-1 changes on a different timescale.

Albumin association changes the size and disposition of the DAC preparation. Jetté and colleagues showed that albumin-associated analogues could retain GH-releasing activity in rat pituitary-cell experiments. That provides a mechanism for prolonged exposure with receptor activity. It also explains why removing the reactive extension is consequential. The remaining core’s exact activity, distribution and disappearance require their own measurements. A related study of a single residue substitution can illuminate degradation biology, but it cannot assign the complete four-substitution fragment a human exposure profile.

Which molecule was tested in people?

CJC-1295 with DAC was administered to healthy adults in blood-concentration and hormone studies. Modified GRF(1–29) without DAC was studied mainly through chemical identification and laboratory breakdown and detection experiments.

CJC-1295 with DAC

  1. Modified GHRH sequence with an added albumin-binding DAC group
  2. Injected under the skin in healthy adults; salt form unspecified
  3. Blood peptide concentrations, growth hormone and IGF-1 measured
  4. Estimated half-life 5.8–8.1 days; recovery from injury not established

Modified GRF(1–29)

  1. 29-residue peptide with four substitutions and an amide end; no DAC group
  2. Chemical identification, laboratory breakdown and detection in urine with added reference material
  3. These experiments identified the peptide and tested how to detect it
  4. Human blood concentrations and clinical benefits still unestablished in these sources

Common source of a mistaken short-duration claim

  1. Natural GHRH(1–29) ↔ singly substituted D-Ala2 analogue
  2. Intravenous infusion in 10 healthy men
  3. The study used a different sequence and intravenous administration
  4. Its result cannot supply the half-life of the peptide with four substitutions
The human studies administered CJC-1295 with its albumin-binding DAC group and measured peptide concentrations, growth hormone and IGF-1. The studies of modified GRF(1–29) without DAC identified the peptide and examined laboratory breakdown and detection. Those studies do not supply the missing human blood-concentration or clinical outcome measurements for the DAC-free peptide. U.S. Food and Drug Administration. FDA Briefing Document: Pharmacy Compounding Advisory Committee Meeting, December 4, 2024. CJC-1295-related bulk drug substances. 2024.; 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, a long-acting analog of GH-releasing hormone, in healthy adults. The Journal of clinical endocrinology and metabolism. 2006;91(3):799–805. DOI: 10.1210/jc.2005-1536. PMID: 16352683.; 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 and metabolism. 2006;91(12):4792–4797. DOI: 10.1210/jc.2006-1702. PMID: 17018654.; Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug testing and analysis. 2010;2(11-12):647–650. DOI: 10.1002/dta.233. PMID: 21204297.; Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug testing and analysis. 2021;13(11-12):1871–1887. DOI: 10.1002/dta.3183. PMID: 34665524.

What was established in the DAC human programme

Teichman and colleagues (2006) reported two randomized, placebo-controlled, double-blind ascending-exposure trials in healthy adults aged 21–61. The single-exposure trial included 42 participants and lasted 28 days; the repeated-exposure trial included 24 and lasted 49 days, as also tabulated in FDA’s primary presentation. CJC-1295 was administered subcutaneously, and the material had DAC; its exact salt form was unspecified.

The reported peptide half-life was 5.8–8.1 days across tested groups. After single exposure, mean GH rose twofold to tenfold for at least six days and mean IGF-1 rose 1.5-fold to threefold for nine to eleven days. Repeated exposure produced cumulative hormone effects. These are three different endpoints: disappearance of the assayed peptide, GH response and IGF-1 response. The trials established prolonged pharmacology in selected healthy volunteers, without measuring improved strength, injury recovery or disease prevention.

Ionescu and Frohman’s 2006 study examined a more detailed physiological question. Twelve healthy men, aged 20–40, underwent blood sampling every twenty minutes during a twelve-hour overnight period before exposure and again one week after a single subcutaneous DAC exposure. Pulse frequency and magnitude remained similar, while trough GH—the concentration between pulses—rose approximately 7.5-fold and mean GH rose approximately 46%.

The preserved pulses coexisted with a higher background level. A description such as “preserves natural pulses” therefore leaves out part of the measured endocrine change unless it includes the trough and mean concentrations. The study concerned DAC material, and no corresponding exact-fragment pulse study was established in the sources reviewed here.

A later proteomic analysis by Sackmann-Sala and colleagues studied serum from eleven men in the earlier cohort before exposure and one week afterward. Changes in several protein spots suggested candidate markers of GH/IGF-1 activity. The overlapping participants make this an additional analysis of the existing physiology cohort, and the measured protein changes remain exploratory markers with unestablished clinical utility.

The DAC-free evidence is principally analytical

Henninge and colleagues (2010) investigated an unknown preparation submitted by Norwegian police and customs authorities. High-resolution tandem mass spectrometry supported a 29-amino-acid sequence with a C-terminal amide, which the paper associated with the name CJC-1295. FDA later assigned this report to the DAC-free material. The experiment illustrates how a shared commercial name can direct a reader toward a human paper that used a different molecule.

Memdouh and colleagues (2021) then examined sermorelin, tesamorelin, CJC-1295 without DAC and CJC-1295 with DAC as separate analytes. They investigated in-vitro metabolism and developed detection methods using urine fortified with known peptides and metabolites. Nineteen major metabolites were characterized across the four-peptide set, and detection limits were generally at or below 1 ng/mL.

Fortified urine allows researchers to test analytical detection amid other sample constituents. It supplies no treated-human concentration-time series, elimination half-life or clinical response. This distinction leaves a specific gap for modified GRF(1–29): the selected sources do not establish quantitative human pharmacokinetics or a controlled clinical outcome for the exact four-substitution DAC-free fragment. Its chemical identification is valuable, while the exposure and benefit questions remain open.

Why the familiar short half-life cannot be assigned here

Soule, King and Millar (1994) compared natural amidated GHRH(1–29) with an analogue bearing only D-alanine at position 2 in ten healthy men. They used a ninety-minute intravenous infusion followed by twenty minutes of additional sampling. The singly substituted analogue disappeared more slowly than the natural fragment. This supports the contribution of that residue to clearance under those conditions.

Modified GRF(1–29) carries four substitutions, and subcutaneous absorption would add another process to the concentration profile. The 1994 infusion result therefore remains a related-material observation. Likewise, the multi-day Teichman estimate belongs to DAC material. A numerical human half-life for the exact DAC-free fragment cannot be derived by borrowing either estimate. The available studies establish measured DAC persistence alongside a still-unresolved human concentration-time course for the exact four-substitution fragment.

Safety information is uneven on both sides

Teichman’s early trial abstract reported no serious adverse reactions. FDA’s more detailed assessment describes injection-site reactions, flushing, headache, gastrointestinal symptoms, transient low blood pressure and increased heart rate in the DAC programme. The agency’s current safety communication also identifies limited clinical data and concerns involving characterization, impurities and immune reactions. Small samples and brief follow-up leave uncommon and delayed harms poorly estimated.

FDA additionally records an unpublished phase 2 trial in HIV-associated lipodystrophy that ended after a participant had an acute myocardial infarction and died. The available account could not establish causality, and complete trial results were unavailable. This event adds an unresolved serious outcome to the early tolerability observations; the available account does not show that CJC-1295 caused the death.

For the exact DAC-free fragment, the analytical studies did not expose human participants. Its presumed shorter persistence therefore cannot establish fewer endocrine effects or better safety. Injectable preparation quality adds a separate issue: peptide-related impurities and aggregates may alter biological activity or provoke immune responses. Neither CJC-1295 with DAC nor modified GRF(1–29) has an FDA-approved medicinal product.

The comparison resolves identity before duration

The clearest difference is the evidence attached to each material. The DAC programme demonstrated prolonged peptide exposure, GH stimulation and IGF-1 responses in healthy adults. The DAC-free literature establishes analytical identity and laboratory detection, while leaving direct human pharmacology and clinical outcomes unresolved in the reviewed sources. There is no verified direct clinical comparison here that assigns superior recovery, body composition or long-term health outcomes to either material.

For future work to close that gap, it would need exact sequence and terminal chemistry, a defined preparation, measured exposure, relevant outcomes and enough follow-up to assess harms. Those elements would allow the relationship between duration and benefit to be tested. Shared ancestry identifies the biological family; keeping the tested molecule beside its result makes the available human evidence interpretable.

Frequently asked questions

Does CJC-1295 acetate tell me whether DAC is present?

Acetate identifies the ion paired with a peptide in a salt. It does not tell you whether the peptide has the albumin-binding DAC addition: both DAC and DAC-free forms have been described as salts. The peptide sequence and the presence of the DAC group are needed to identify which molecule was tested.

Is a 30-minute human half-life established for modified GRF(1–29)?

The reviewed primary studies do not establish that value for the exact four-substitution fragment. The DAC trials and the singly substituted D-Ala2 infusion study used different materials.

Did the DAC pulse study show unchanged growth-hormone exposure?

The investigators sampled blood overnight in healthy men before and one week after CJC-1295 with DAC. GH pulses remained similar in frequency and size, but the concentration between pulses and the average concentration increased. The hormone pattern therefore changed even though its pulses persisted.

Does detection in fortified urine show how long a person excretes the fragment?

The investigators added known reference materials to urine to assess detection. An excretion timeline requires samples collected after a defined human exposure.

References

  1. U.S. Food and Drug Administration. FDA Briefing Document: Pharmacy Compounding Advisory Committee Meeting, December 4, 2024. CJC-1295-related bulk drug substances. 2024.

    Official FDA primary briefing opened on 2026-10-14; chemistry and human-study passages read directly or through indexed FDA PDF text. PDF indexes 8–20: identities; 35–45: human studies and safety; 49–52 effectiveness conclusions. Human preparation had DAC with unspecified salt form.

  2. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052–3058. DOI: 10.1210/en.2004-1286. PMID: 15817669.

    Original indexed PubMed abstract and original Oxford publisher record read on 2026-10-14. Abstract: albumin bioconjugation, rat anterior pituitary cells and rat exposure.

  3. 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, a long-acting analog of GH-releasing hormone, in healthy adults. The Journal of clinical endocrinology and metabolism. 2006;91(3):799–805. DOI: 10.1210/jc.2005-1536. PMID: 16352683.

    Original indexed PubMed abstract read on 2026-10-14. Original Table 1/Results checked in indexed government-hosted reprint; direct reprint download returned 403. Sample sizes cross-checked against FDA primary slides. Table 1: single-exposure trial n=42, repeated-exposure trial n=24. Abstract: 28/49-day trials, healthy adults ages 21–61, subcutaneous DAC preparation, estimated 5.8–8.1-day half-life.

  4. 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 and metabolism. 2006;91(12):4792–4797. DOI: 10.1210/jc.2006-1702. PMID: 17018654.

    Original indexed PubMed abstract checked on 2026-10-14; detailed mean/trough results and n=12 cross-checked in FDA’s primary assessment. Methods: 20-minute sampling over 12 hours before and one week after single subcutaneous exposure; healthy men ages 20–40. Results: preserved pulse frequency/magnitude, higher mean/trough GH.

  5. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2009;19(6):471–477. DOI: 10.1016/j.ghir.2009.03.001. PMID: 19386527.

    Original indexed PubMed abstract and original figure descriptions read on 2026-10-14; overlapping cohort mapping retained from reviewed profile’s original source extraction. 11 men from earlier pulsatility cohort; serum before/one week after exposure; proteomic candidate markers.

  6. Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug testing and analysis. 2010;2(11-12):647–650. DOI: 10.1002/dta.233. PMID: 21204297.

    Original indexed PubMed abstract and original indexed Wiley abstract read on 2026-10-14. Unknown preparation submitted by Norwegian police/customs; 29 amino acids and C-terminal amide; FDA maps report to DAC-free material.

  7. Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug testing and analysis. 2021;13(11-12):1871–1887. DOI: 10.1002/dta.3183. PMID: 34665524.

    Original indexed PubMed abstract and original indexed Wiley full-text introduction/conclusions read on 2026-10-14. Four distinct GHRH analogues; in-vitro metabolism; 19 metabolites across set; fortified urine; generally ≤1 ng/mL detection limits.

  8. Soule S, King JA, Millar RP. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. The Journal of clinical endocrinology and metabolism. 1994;79(4):1208–1211. DOI: 10.1210/jcem.79.4.7962295. PMID: 7962295.

    Original indexed PubMed abstract and original Oxford publisher abstract read on 2026-10-14. Ten healthy men; native GHRH(1–29)-amide versus singly substituted D-Ala2 analogue; 90-minute intravenous infusion plus 20-minute post-infusion sampling. Different material from tetrasubstituted modified GRF.

  9. Gajda PM, Holm NB, Hoej LJ, Rasmussen BS, Dalsgaard PW, Reitzel LA, Linnet K. Glycine-modified growth hormone secretagogues identified in seized doping material. Drug testing and analysis. 2019;11(2):350–354. DOI: 10.1002/dta.2489. PMID: 30136411.

    Original indexed PubMed and original indexed Wiley abstract read on 2026-10-14. Seized Danish preparations; N-terminal extra glycine on modified GRF-related peptide; no administered-human efficacy experiment.

  10. U.S. Food and Drug Administration. CJC-1295-related bulk drug substances: FDA presentation to the Pharmacy Compounding Advisory Committee. December 4, 2024.

    Original indexed FDA slide content checked on 2026-10-14. Slide 63: Teichman trial populations n=42 and n=24; Ionescu/Frohman population twelve healthy men.

  11. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. Current agency safety communication; checked October 14, 2026.

    Official FDA page opened on 2026-10-14. CJC-1295 entry: immunogenicity, characterization, limited clinical data, increased heart rate and systemic vasodilatory reaction.