Key Takeaways
- The DAC modification extends half-life from roughly 30 minutes to approximately 6 to 8 days by covalently bonding to serum albumin at Cys34, confirmed in a phase II human trial (Teichman et al., 2006).
- That same trial showed mean IGF-1 increases of roughly 1.5 to 3-fold above baseline at doses of 60 to 90 mcg/kg, the only published human dose-response data that exist.
- No published human RCT has tested body composition, muscle gain, or fat loss endpoints for this specific compound, so performance claims are extrapolations from GH physiology, not direct evidence.
- CJC-1295 with DAC and CJC-1295 without DAC (Mod GRF 1-29) are pharmacokinetically distinct compounds and are not interchangeable in protocol design.
- WADA lists GHRH analogues including CJC-1295 as prohibited (S2 class), and the compound is not FDA approved for any use.
What is CJC-1295 with DAC, and how quickly does it work?
Table of Contents
- What does the DAC modification actually do at the molecular level?
- Evidence ledger: what is actually proven?
- What is the correct CJC-1295 with DAC dosing protocol?
- How does stacking CJC-1295 with DAC with Ipamorelin work?
- Head-to-head: CJC-1295 with DAC vs. its real alternatives
- What most pages get wrong about CJC-1295 with DAC
- Formulation and stability: the chemistry behind the rules
- How to read a COA and judge product quality
- Side effects and risk profile
- FAQ
- Sources
What does the DAC modification actually do at the molecular level?
Native GHRH(1-29) is cleared by dipeptidyl peptidase IV (DPP-IV) cleavage at the Ala2-Asp3 bond and by renal filtration. Its plasma half-life is under 10 minutes. CJC-1295 with DAC addresses both problems.
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Try the BMI Calculator →The compound starts with the same four amino-acid substitutions found in Mod GRF 1-29 (positions 2, 8, 15, and 27 are substituted to resist DPP-IV cleavage). Then a Drug Affinity Complex linker, specifically a maleimide group attached via a polyethylene glycol spacer to the epsilon-amine of a lysine residue added at position 33, is incorporated. When injected subcutaneously, this maleimide reacts with the free thiol of Cys34 on circulating serum albumin via a Michael addition reaction, forming a stable thioether bond.
Serum albumin has a molecular weight of approximately 67 kDa, which places it well above the glomerular filtration threshold. Albumin also has a circulatory half-life of roughly 19 days in healthy adults due to FcRn-mediated recycling. The result is that CJC-1295 with DAC acquires a dramatically extended half-life, measured at approximately 6 to 8 days in the Teichman 2006 phase II trial.
What this mechanism does NOT prove: prolonged receptor occupancy at the pituitary GHRH receptor does not automatically translate to proportionally greater GH output. Pulsatile GH secretion involves feedback regulation via somatostatin, and chronic GHRH-receptor stimulation may trigger receptor downregulation. The clinical relevance of this blunting is unknown because long-term human data are absent.
Evidence ledger: what is actually proven?
| Claim | Best evidence type | Key source | Effect direction | Confidence |
|---|---|---|---|---|
| Extended half-life (~6 to 8 days) via albumin binding | Human phase II PK trial | Teichman et al., 2006 (J Clin Endocrinol Metab) | Confirmed | High |
| Raises GH above baseline for multiple days | Human phase II trial | Teichman et al., 2006 | Positive, dose-dependent | High |
| Raises IGF-1 ~1.5 to 3x baseline | Human phase II trial | Teichman et al., 2006 | Positive | Moderate (single trial, small n) |
| Improves lean body mass or reduces fat mass | Mechanism extrapolation only | None (no human RCT) | Theoretical | Very low |
| Improves recovery or exercise performance | Mechanism extrapolation only | None (no human RCT) | Theoretical | Very low |
| Synergistic GH release when stacked with GHRP/ghrelin agonist | Animal and in vitro data; GHRH+GHRP synergy established in humans with other analogues | Bowers et al. general literature; no DAC-specific human stack RCT | Probably positive | Low |
| Safe for long-term human use | No long-term safety trial | None | Unknown | Very low |
What is the correct CJC-1295 with DAC dosing protocol?
The only published human dose-response data come from Teichman et al. (2006), which tested single subcutaneous doses ranging from 30 to 120 mcg/kg in healthy adults aged 21 to 61. The doses of 60 and 90 mcg/kg produced the most consistent GH and IGF-1 elevation with acceptable tolerability. For a 80 kg person, 60 mcg/kg equals 4,800 mcg (4.8 mg). That is a single-dose pharmacokinetic trial, not a multi-dose optimization study.
Investigational community protocols typically reference 1,000 to 2,000 mcg once weekly or once every two weeks, based on the long half-life. These fixed milligram figures are not directly drawn from a published clinical dose-escalation table. They represent a pragmatic extrapolation. No peer-reviewed study has compared 1,000 mcg weekly to 2,000 mcg biweekly for any outcome in humans.
Practical dosing considerations
- Because the half-life is approximately 6 to 8 days, daily injection offers no pharmacokinetic rationale. Once-weekly administration is the pharmacologically logical interval.
- Subcutaneous injection into abdominal or lateral thigh fat is the standard route. Intramuscular use is not supported by any published protocol.
- Administration timing relative to meals matters less for CJC-1295 with DAC than for shorter-acting GHRH analogues, because the prolonged half-life means GH pulses are not tied to a single injection moment.
- Cycle duration is unstudied. The theoretical concern about pituitary desensitization with chronic continuous GHRH-receptor stimulation has not been quantified in humans.
How does stacking CJC-1295 with DAC with Ipamorelin work?
GH secretion from the pituitary is governed by two main inputs: stimulation via the GHRH receptor and stimulation via the ghrelin receptor (GHSR-1a). These pathways are synergistic, meaning co-activation produces greater GH output than either pathway alone. This synergy is well established in human studies using other GHRH analogues combined with GHRP-6 or hexarelin.
Ipamorelin is a selective GHSR-1a agonist. It stimulates GH release with minimal effect on cortisol or prolactin compared to older GHRPs, which is why it is the most commonly paired agent. The theoretical case for the CJC-1295 with DAC plus Ipamorelin stack rests on this established GHRH-GHRP synergy mechanism, but the specific combination has not been tested in a published human trial.
Stack protocol considerations
| Agent | Receptor target | Half-life | Injection frequency | Evidence for combination |
|---|---|---|---|---|
| CJC-1295 with DAC | GHRH-R | ~6 to 8 days | Once weekly | No human RCT for this combo |
| Ipamorelin | GHSR-1a | ~2 hours | Daily to three times daily | No human RCT for this combo |
The pharmacokinetic mismatch between the two compounds is important. CJC-1295 with DAC provides a tonic, blunted GH background. Ipamorelin, dosed before sleep or post-exercise, adds pulsatile spikes on top of that baseline. Whether this produces meaningfully better outcomes than either alone in humans is unknown.
Head-to-head: CJC-1295 with DAC vs. its real alternatives
| Compound | Mechanism | Human evidence quality | Half-life | GH pattern | Where CJC-DAC loses |
|---|---|---|---|---|---|
| CJC-1295 with DAC | GHRH-R agonist, albumin-bound | One phase II PK trial | ~6 to 8 days | Prolonged tonic elevation | Blunts natural pulsatility; no body composition RCT |
| Mod GRF 1-29 (CJC-1295 no DAC) | GHRH-R agonist, unmodified PK | Limited human PK data | ~30 minutes | Single pulse per injection | Requires daily injections to sustain elevation |
| Sermorelin | GHRH(1-29) agonist | Multiple human trials, some body composition data in GH-deficient adults | ~10 to 12 minutes | Single pulse | Shortest half-life; was FDA approved (discontinued), more established safety record |
| Tesamorelin | GHRH analogue | Multiple phase III RCTs; FDA approved for HIV-associated lipodystrophy | ~26 minutes | Daily pulse | CJC-DAC has no approved indication; tesamorelin wins on evidence and regulatory status |
| rhGH (Somatropin) | Direct GH receptor agonist | Extensive RCT data, FDA approved for multiple indications | ~3 to 4 hours | Non-pulsatile elevation | CJC-DAC loses on every regulatory and evidence dimension; rhGH wins |
What most pages get wrong about CJC-1295 with DAC
Most content conflates CJC-1295 with DAC and CJC-1295 without DAC (Mod GRF 1-29) as if they are the same compound with a minor labeling difference. They are not. The DAC version requires once-weekly injection because of albumin binding. The no-DAC version requires daily injection to sustain any GH elevation. Using a once-weekly DAC protocol with Mod GRF 1-29 produces minimal effect. Using a daily injection schedule with the DAC version accumulates drug over weeks and risks sustained supraphysiologic GH levels. Mixing up the two is a meaningful clinical error.
A second omission is the conflation of GH elevation with body composition outcomes. Raising IGF-1 and GH in healthy adults with normal baseline GH does not reliably produce lean mass gain. The body composition benefits of GH are most pronounced in GH-deficient populations. Studies of supraphysiologic GH administration in healthy adults (rhGH trials) show modest lean mass gains that largely reverse after cessation. Extrapolating from those findings to CJC-1295 with DAC in a healthy adult adds two additional inferential steps, neither of which is supported by published trial data.
Third, commodity pages routinely quote specific "optimal dose" figures with false precision. The only published human dose data are weight-based single-dose pharmacokinetic observations from Teichman 2006. Fixed milligram weekly doses are community extrapolations.
Formulation and stability: the chemistry behind the rules
The DAC linker is a maleimide-based reactive group. Maleimides are susceptible to hydrolysis, particularly at pH above 7 and at elevated temperatures. Hydrolysis of the maleimide ring to a maleamic acid derivative reduces its reactivity with albumin thiol groups, which means degraded product may have a significantly shortened half-life despite appearing visually identical to intact peptide.
This is why reconstitution temperature and pH matter. Using sterile water without a pH buffer or using water that has been stored warm accelerates this degradation. Bacteriostatic water (0.9% benzyl alcohol in water for injection) does not prevent maleimide hydrolysis, but it does inhibit microbial contamination in multi-use vials, which is a separate and important concern.
Lyophilized (freeze-dried) powder is stable at 2 to 8 degrees Celsius under proper conditions because the absence of free water dramatically slows hydrolysis. Once reconstituted, the peptide should be stored refrigerated, protected from light (peptide bonds are susceptible to UV photolysis), and used within the timeframe specified on the supplier certificate of analysis. Repeated freeze-thaw cycling of reconstituted solution promotes aggregation and should be avoided.
Do not reconstitute with plain tap water or saline solutions. Saline contains chloride ions that can promote metal-catalyzed oxidation of methionine residues in the peptide sequence. Use bacteriostatic water for injection (USP grade) or sterile water for injection.
How to read a COA and judge product quality
A legitimate certificate of analysis for CJC-1295 with DAC should contain all of the following. If any element is absent, that is a red flag, not a minor omission.
| COA element | What to look for | Why it matters |
|---|---|---|
| HPLC purity | Greater than 98% by area under the curve | Confirms the correct compound is the dominant species; impurities can include truncated sequences or synthesis byproducts |
| Mass spectrometry (MS) | Molecular weight matching ~3367 Da (verify against the published sequence) | Confirms the correct compound; will expose substitution of cheaper analogues or the no-DAC version |
| Endotoxin (LAL test) | Below 1 EU/mg for research use; stricter limits apply for any clinical use | Lipopolysaccharide contamination from bacterial synthesis causes fever and systemic inflammation |
| Sterility | Negative for bacterial and fungal contamination | Required for injectable use |
| Amino acid analysis | Confirms sequence composition | Detects sequence truncations that HPLC may miss if they co-elute |
| Batch/lot number | Must be traceable to testing lab | Generic or undated COAs may not correspond to the actual batch received |
A COA dated more than 12 months before receipt, lacking a third-party lab name, or showing purity below 95% should be rejected. The molecular weight verification via MS is the single most important test for distinguishing CJC-1295 with DAC from Mod GRF 1-29, because they share sequence similarity but have different molecular weights due to the DAC linker.
Side effects and known risk profile
The Teichman 2006 trial reported that injection site reactions (erythema, swelling, pain) were the most common adverse events. Water retention and peripheral edema were reported in a minority of subjects, consistent with the known effects of GH elevation on sodium and water handling. No serious adverse events were reported in that single-dose trial.
The theoretical risks of chronic use are significant and unstudied in this specific compound:
- Insulin resistance: GH is a counter-regulatory hormone to insulin. Sustained GH elevation has well-established glucose-raising effects. Long-term impact on insulin sensitivity with weekly CJC-1295 with DAC is unknown.
- Neoplasia: IGF-1 is a mitogenic signal. GH/IGF-1 elevation is thought to promote growth of pre-existing neoplastic tissue. This is a theoretical concern; no causal link to new cancer formation from short-term GHRH analogue use has been demonstrated in humans.
- Somatostatin rebound: chronic GHRH-receptor stimulation may upregulate somatostatin tone, potentially blunting the natural GH axis after discontinuation. Duration and reversibility are unknown.
- Acromegalic changes: sustained supraphysiologic GH/IGF-1 elevation over months to years, as seen in acromegaly, produces soft tissue and skeletal changes. Whether investigational CJC-1295 with DAC protocols can reach this threshold is unknown.
FAQ
What is CJC-1295 with DAC?
CJC-1295 with DAC is a synthetic 30-amino-acid GHRH analogue modified with a Drug Affinity Complex (DAC) lysine-maleimide linker that covalently binds to serum albumin, extending its half-life from roughly 30 minutes to approximately 6 to 8 days in humans.
What does the DAC modification actually do?
DAC stands for Drug Affinity Complex. It adds a maleimide-PEG linker at Lys33 that forms a covalent thioether bond with Cys34 of serum albumin. Because albumin has a molecular weight of roughly 67 kDa and avoids kidney filtration, the peptide circulates far longer than unmodified analogues.
What is the typical CJC-1295 with DAC dose?
The phase II trial by Teichman et al. (2006) used single doses of 60 to 90 mcg/kg in healthy adults and found sustained GH elevation for up to 6 days. Investigational protocols commonly reference 1,000 to 2,000 mcg once weekly, but no human dose-optimization RCT has been published at those fixed milligram doses.
How does CJC-1295 with DAC differ from CJC-1295 without DAC?
CJC-1295 without DAC (also called Modified GRF 1-29 or Mod GRF) has a half-life of roughly 30 minutes and produces a single GH pulse when injected. CJC-1295 with DAC produces a prolonged, blunted GH elevation over days. The two compounds have meaningfully different pharmacokinetic profiles and are not interchangeable.
Is CJC-1295 with DAC FDA approved?
No. CJC-1295 with DAC is not FDA approved for any indication. It remains an investigational research compound. It is not available as a compounded medication in the United States under current FDA guidance on bulk drug substances.
What does stacking CJC-1295 with DAC with Ipamorelin add?
Ipamorelin is a ghrelin-receptor agonist (GHSR agonist) that stimulates GH release through a different receptor pathway than GHRH. Preclinical data suggest GHRH analogues and GHRP/ghrelin agonists act synergistically. However, no published human RCT has tested the specific CJC-1295 DAC plus Ipamorelin combination.
What are the main risks or side effects?
Reported effects in the Teichman 2006 trial included injection-site reactions and transient water retention. Sustained supraphysiologic GH elevation raises theoretical concerns about insulin resistance, potential promotion of pre-existing neoplasia, and acromegalic changes with chronic use, though no long-term human safety data exist.
How should CJC-1295 with DAC be stored and reconstituted?
Lyophilized powder should be stored at 2 to 8 degrees Celsius and protected from light. Reconstitute with bacteriostatic water, not plain sterile water, to inhibit microbial growth. Once reconstituted, solutions degrade faster at room temperature. The maleimide linker is sensitive to hydrolysis, so reconstituted product should be used within the period specified by the supplier COA.
Does CJC-1295 with DAC raise IGF-1?
Yes. The Teichman 2006 phase II trial reported mean IGF-1 increases of roughly 1.5 to 3-fold above baseline in healthy adults following single doses of 60 to 90 mcg/kg. IGF-1 elevation followed GH elevation with the expected hepatic lag.
How do I read a COA for CJC-1295 with DAC?
A trustworthy COA should include HPLC purity greater than 98 percent, mass spectrometry confirmation of the correct molecular weight (approximately 3367 Da for the full DAC-modified sequence), endotoxin testing below 1 EU/mg, and sterility confirmation. Absence of any of these data points is a red flag.
Is CJC-1295 with DAC on the WADA prohibited list?
Yes. GHRH analogues including CJC-1295 appear on the WADA prohibited list under peptide hormones, growth factors, and related substances (S2). Use in competitive sport is banned both in and out of competition.
What does the evidence NOT prove about CJC-1295 with DAC?
The existing human data prove that CJC-1295 with DAC raises GH and IGF-1. They do not prove that this translates to meaningful muscle gain, fat loss, or recovery improvement in healthy adults. Body composition endpoints have not been assessed in published human trials of this specific compound.
Sources
- 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. J Clin Endocrinol Metab. 2006;91(3):799-805.
- Frohman LA, Jansson JO. Growth hormone-releasing hormone. Endocr Rev. 1986;7(3):223-253.
- Bowers CY. Growth hormone-releasing peptide (GHRP). Cell Mol Life Sci. 1998;54(12):1316-1329.
- Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. (Tesamorelin phase III context.)
- World Anti-Doping Agency. 2025 Prohibited List. S2. Peptide Hormones, Growth Factors, Related Substances and Mimetics. WADA, 2025.
- Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab. 1992;75(2):530-535.
- Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990;323(1):1-6.
- Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults. Ann Intern Med. 2008;149(9):601-611.
- FDA. Bulk Drug Substances Under Section 503A and 503B of the FD&C Act. Federal Register guidance documents, 2023 to 2025.
- U.S. Pharmacopeia (USP). General Chapter 1 (Injections and Implanted Drug Products). USP-NF.
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