CJC-1295 with DAC — Half-Life, Pharmacokinetics & Protocol Guide
Also known as: CJC-1295 DAC · Drug Affinity Complex CJC-1295 · DAC:GRF
Class: Long-acting GHRH (growth hormone releasing hormone) analogue. The Drug Affinity Complex (DAC) — maleimido caproic acid at Lys30 — enables covalent binding to circulating albumin Cys34, extending plasma half-life from ~30 minutes to ~6–8 days.
Human PK Study ·
Teichman et al. J Clin Endocrinol Metab. 2006 · PMID 16352683
Halflife Labs Research Team|May 2026|Human PK Study
Plasma Half-Life
~6–8 days
Source: Teichman SL et al. J Clin Endocrinol Metab. 2006;91(3):799–805. PMID 16352683 — human PK study
Tmax
~2 days
Route
Subcutaneous (SC) injection
Typical Dosing Frequency
Once or twice weekly
Steady State
~4–5 weeks
Near-Complete Clearance (5 half-lives)
~30–40 days
IGF-1 Elevation Duration (single dose)
Up to 14 days (Teichman 2006)
FDA Status
Not approved — research chemical
Data Quality
Human PK Study
SC Bioavailability
Not fully published; presumed high
GH Pulsatility Concern: Unlike CJC-1295 without DAC, the DAC version creates continuous sustained GHRH stimulation. This may blunt normal episodic GH pulse patterns and potentially downregulate GHRH receptors with chronic use. No long-term human safety data is available on this specific concern. This is a key differentiator from the no-DAC version in research protocol design.
Mechanism of Action
1. GHRH Receptor Agonism
CJC-1295 (with or without DAC) contains the first 29 amino acids of native growth hormone releasing hormone (GHRH) with four amino acid substitutions that confer resistance to dipeptidyl peptidase IV (DPP-4), the enzyme that rapidly degrades native GHRH. It activates the GHRH receptor (GHRHR) expressed on pituitary somatotroph cells via Gs protein coupling, driving adenylyl cyclase to increase intracellular cAMP. This activates protein kinase A (PKA), which stimulates GH synthesis and release. The primary effect is to expand the releasable pool of GH in somatotrophs, as opposed to GH-releasing peptides (GHRPs) which primarily amplify pulse amplitude through ghrelin receptor signalling.
2. DAC Chemistry and Albumin Binding
The Drug Affinity Complex (DAC) is a maleimido caproic acid (MCA) reactive group attached to Lys30 of the peptide. After subcutaneous injection, the maleimide reacts with the free thiol group of Cys34 on circulating serum albumin via a near-irreversible Michael addition reaction, forming a stable covalent albumin-peptide conjugate. Since human serum albumin has its own extended half-life of approximately 19 days — maintained by FcRn (neonatal Fc receptor) recycling — the CJC-1295-albumin complex benefits from this protection from proteolytic degradation and renal clearance. The result is a plasma half-life of approximately 6–8 days, compared to approximately 30 minutes for CJC-1295 without the DAC modification.
3. GH Pulsatility Concern
Unlike CJC-1295 without DAC (Mod GRF 1-29), which is cleared quickly and thus preserves the natural episodic GH pulse pattern by stimulating only transiently, the DAC version maintains near-continuous GHRH stimulation for days to weeks. Continuous GHRH receptor activation may suppress the normal pulsatile GH secretion that is physiologically important for anabolic signalling, lipid metabolism, and sleep architecture. There is also a theoretical risk of GHRH receptor downregulation with sustained stimulation over longer treatment periods. No long-term human safety data is available to quantify this risk. Ionescu and Frohman (2006, PMID 17003086) demonstrated that pulsatile GH secretion persists to some degree during continuous CJC-1295 stimulation, though the pulse amplitude and pattern differ from normal physiology.
Three-Layer Pharmacokinetic Model
Understanding CJC-1295 DAC clearance requires three distinct timescales:
Layer 1 — Plasma Half-Life
~6–8 days Teichman et al. 2006, PMID 16352683
Layer 2 — Near-Complete Clearance
~30–40 days (5 half-lives)
Layer 3 — Downstream Biomarker Effects
IGF-1 elevated up to 14 days after a single dose (Teichman 2006); GH pulsatility suppression may persist beyond peptide clearance. Repeated dosing sustained IGF-1 at ~20–30% above baseline throughout the study duration.
Clearance Timeline
Using a median half-life of 7 days for estimation. Values represent approximate percentage of dose remaining in plasma.
Time After Dose
Half-Lives Elapsed
% Remaining (Approx.)
Clinical Relevance
Day 2
0.3
~80%
Tmax — peak plasma concentration
Day 7
1.0
~50%
One half-life elapsed; IGF-1 still substantially elevated
Day 14
2.0
~25%
IGF-1 elevation may persist to this point (single dose)
Day 21
3.0
~12.5%
Significant residual GHRH activity
Day 28
4.0
~6%
Approaching washout
Day 35
5.0
~3%
Near-complete clearance (~5 half-lives)
Routes of Administration
Route
Status
Notes
Subcutaneous (SC)
Primary research route
Human PK data available (Teichman 2006)
Intravenous (IV)
Used in original research
Not a practical clinical or research route
Intramuscular (IM)
No published data
Not studied; extrapolation not validated
Oral
Not bioavailable
Peptide is degraded by gastric acid and gut proteases
Note: Tesamorelin (Egrifta) is the only FDA-approved GHRH analogue and is indicated solely for HIV-associated lipodystrophy. All other compounds in this table are unapproved research chemicals.
Safety Considerations
Important safety information: CJC-1295 with DAC has not undergone large-scale human safety trials. Key concerns include: (1) theoretical GHRH receptor downregulation with chronic continuous stimulation; (2) supraphysiologic IGF-1 levels may have proliferative effects in theoretical models; (3) no FDA approval for any indication; (4) no established safe or effective dose in humans. Use of CJC-1295 DAC is at the individual's own risk. This page is for educational and research reference purposes only — it does not constitute medical advice.
Frequently Asked Questions
What is the half-life of CJC-1295 with DAC?
Approximately 6–8 days, based on human pharmacokinetic data. The definitive citation is: Teichman SL, Neale A, Lawrence B, et al. 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. PMID 16352683. This is one of the only human PK studies for any GHRH analogue of this class.
What does DAC stand for in CJC-1295?
DAC stands for Drug Affinity Complex. It refers to a maleimido caproic acid (MCA) reactive group covalently attached to Lys30 of the peptide. After subcutaneous injection, the maleimide undergoes a Michael addition reaction with the free thiol (–SH) of Cys34 on circulating serum albumin, forming a stable covalent bond. This albumin conjugation strategy extends the half-life from approximately 30 minutes (without DAC) to approximately 6–8 days.
How often is CJC-1295 DAC typically dosed in research protocols?
Based on the ~6–8 day half-life, most research protocols use once or twice weekly dosing. A single dose of CJC-1295 DAC was shown to produce measurable IGF-1 elevation for up to 14 days in the Teichman et al. 2006 human study (PMID 16352683). This means weekly injections create overlapping pharmacodynamic effects, contributing to sustained IGF-1 elevation above baseline.
Does CJC-1295 DAC blunt GH pulsatility?
Potentially yes. The continuous, long-lasting GHRH stimulation from the DAC version contrasts sharply with the brief, episodic stimulation of the no-DAC version (Mod GRF 1-29). Sustained GHRH receptor activation may suppress normal pulsatile GH release and could lead to receptor downregulation. Ionescu and Frohman (PMID 17003086) found pulsatility persists to some degree, but the pattern is altered. This GH pulsatility concern is a key differentiator from the no-DAC version and is actively debated in the research community. No long-term human data is available.
Is CJC-1295 with DAC FDA approved?
No. CJC-1295 with DAC is not FDA approved for any indication. It is classified as a research chemical. The only FDA-approved GHRH analogue is tesamorelin (Egrifta, Theratechnologies), which is indicated solely for the treatment of HIV-associated lipodystrophy. Any other use of GHRH analogues — including CJC-1295 DAC — is off-label or outside the regulatory framework entirely.
What is the difference between CJC-1295 with DAC and CJC-1295 without DAC?
The key differences are pharmacokinetic and pharmacodynamic. CJC-1295 with DAC has a half-life of ~6–8 days, enabling once-weekly dosing, but produces continuous GHRH stimulation that may blunt natural GH pulsatility. CJC-1295 without DAC (also called Mod GRF 1-29) has a half-life of approximately 30 minutes, requires injection at the same time as each GHRP dose, but preserves the episodic, pulsatile GH release pattern that many researchers consider more physiologically appropriate. The no-DAC version pairs more cleanly with GHRPs like ipamorelin for additive GH pulse amplification.
How long does CJC-1295 DAC keep IGF-1 elevated?
In the Teichman et al. 2006 human study (PMID 16352683), a single injection of CJC-1295 DAC elevated serum IGF-1 for up to 14 days. With repeated weekly or twice-weekly dosing, IGF-1 was maintained at approximately 20–30% above baseline throughout the duration of the study. This makes CJC-1295 DAC distinct from shorter-acting GH axis compounds where IGF-1 returns to baseline between doses.
Can CJC-1295 with DAC be combined with ipamorelin?
In research protocols, CJC-1295 DAC is sometimes combined with ipamorelin (a GHRP / ghrelin receptor agonist). However, the synergy may be less optimal than CJC-1295 no-DAC + ipamorelin. The no-DAC version's transient GHRH signal aligns with ipamorelin's pulsatile GH release, mimicking natural physiology more closely. The DAC version's sustained GHRH tone may suppress the native pulsatile GH secretion that ipamorelin is designed to amplify. This is a topic of active debate in the research community; no human randomised controlled trial data exists for either combination.
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Teichman SL, Neale A, Lawrence B, et al. 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. PMID 16352683. [Primary human PK study — t½ ~6–8 days, IGF-1 elevation up to 14 days, single dose; 28-day repeat dosing data]
Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792–4797. PMID 17003086. [Demonstrates partial preservation of GH pulsatility during continuous GHRH stimulation]