CJC-1295 DAC: The Long-Acting GHRH Analog — Pharmacology and Research

Research Disclaimer: CJC-1295 is sold exclusively for in-vitro and laboratory research use. Not approved for human therapeutic use. This content does not constitute medical advice.

CJC-1295 occupies a unique position in GH research: it is the longest-acting GHRH analog studied, capable of maintaining elevated growth hormone-releasing activity for up to 8 days following a single injection. This extraordinary half-life extension — from 7 minutes for native GHRH to 6–8 days for CJC-1295 with DAC — is achieved through a single chemical modification: addition of a drug affinity complex (DAC) that enables reversible albumin binding.

Understanding how this modification works, and how it changes the pharmacokinetics and research applications of CJC-1295, is essential for designing appropriate GH axis research protocols.

Table of Contents#

1. What Is GHRH and Why Is a Long-Acting Analog Needed?
2. CJC-1295 Without DAC (Mod-GRF 1-29)
3. The DAC Modification: Albumin Binding Chemistry
4. Pharmacokinetics: Half-Life Comparison
5. GH Release: Acute and Chronic Profiles
6. IGF-1 Elevation Data from Published Studies
7. With DAC vs. Without DAC: Which for Your Research?
8. Protocol Design
9. Combination with Ipamorelin
10. Frequently Asked Questions
11. Key References

What Is GHRH and Why Is a Long-Acting Analog Needed?#

GHRH (Growth Hormone-Releasing Hormone) is a 44-amino-acid peptide produced by the hypothalamus that drives pituitary somatotrophs to synthesize and release GH. It is the primary "on switch" for GH secretion.

Problems with using native GHRH in research:

1. Half-life of ~7 minutes: rapidly cleaved by plasma dipeptidylpeptidase IV (DPP-IV) at the N-terminal Tyr-Ala bond
2. Unstable in plasma: beyond DPP-IV, other plasma peptidases cleave additional sites
3. Requires frequent IV administration for sustained GH elevation
4. Not orally bioavailable

These limitations prompted development of GHRH analogs with improved stability — modifications to resist DPP-IV and extend the half-life enough to allow SC administration and maintain a prolonged GH-releasing signal.

CJC-1295 Without DAC (Mod-GRF 1-29)#

The first version of CJC-1295 — sometimes called Modified GRF(1-29) or "Mod-GRF" — is a 29-amino-acid GHRH analog with four specific amino acid substitutions from native GHRH:

1. Position 2: Ala → D-Ala (DPP-IV resistance — prevents the primary cleavage site)
2. Position 8: Asn → Gln (prevents deamidation)
3. Position 15: Gly → Ala (improves stability)
4. Position 27: Met → Nle (prevents methionine oxidation)

These four changes produce a GHRH analog with:

• DPP-IV resistance: the primary plasma cleavage site is blocked
• Plasma half-life: 30–60 minutes (vs. 7 minutes for native GHRH)
• Retained full agonist activity at GHRH-R
• SC bioavailability: absorption is sufficient for SC dosing

Mod-GRF (1-29) is the preferred form for research requiring pulsatile GH dynamics — it is dosed 2–3× daily alongside Ipamorelin, producing discrete GH pulses that mimic natural pulsatile GH secretion.

The DAC Modification: Albumin Binding Chemistry#

The CJC-1295 with DAC form adds a further modification to Mod-GRF: a maleimide-containing linker attached to the lysine side chain at position 28 (a substituted Lys replaces the native Arg at position 29, with the DAC linker).

How the DAC works#

Serum albumin is the most abundant plasma protein (35–50 g/L in humans) and has a circulating half-life of approximately 19 days. Albumin has a specific free thiol group on Cys-34 that reacts with maleimide groups through Michael addition — a specific, covalent but slowly reversible conjugation.

The DAC linker on CJC-1295 with DAC:

1. Reacts with albumin Cys-34 after injection → forms CJC-1295-albumin conjugate
2. The albumin complex is now ≈67 kDa (above the renal filtration threshold of 30–50 kDa) → not filtered by the kidney
3. CJC-1295 slowly hydrolyzes off the albumin conjugate over 6–8 days → gradual release of active CJC-1295
4. Released CJC-1295 binds pituitary GHRH-R → GH release
5. Freed CJC-1295 is then rapidly cleared

The result: a single injection of CJC-1295 with DAC creates a reservoir of albumin-bound peptide that slowly releases active compound over days — providing sustained GHRH-R stimulation from a single weekly injection.

Pharmacokinetics: Half-Life Comparison#

The 6–8 day half-life of CJC-1295 with DAC was confirmed in humans (Teichman et al. 2006):

• Single SC injection (30–60 µg/kg): measurable elevated GH for 6 days, elevated IGF-1 for 9–11 days
• Multiple weekly injections: sustained elevated GH and IGF-1 throughout the dosing period

GH Release: Acute and Chronic Profiles#

With DAC (single dose)#

Unlike pulsatile GHRP or Mod-GRF injections, CJC-1295 with DAC produces a sustained, non-pulsatile elevation in GH. Because active CJC-1295 is continuously released from the albumin depot and activating GHRH-R, the pituitary is under continuous (though variable) GHRH stimulation throughout the week.

This is pharmacologically distinct from physiological GH secretion — endogenous GH is pulsatile, with low baseline between pulses. CJC-1295 with DAC creates a non-physiological GH profile.

Research implications of non-pulsatile GH#

Whether pulsatile vs. sustained GH is preferred depends on the research question:

• Pulsatile GH preserves GH receptor sensitivity (periodic receptor "rest" prevents downregulation)
• Sustained GH may cause GH receptor downregulation with chronic exposure — similar to what is seen with recombinant GH
• For endpoint-focused studies (does elevated GH/IGF-1 → increased lean mass?), either profile works
• For mechanistic studies of GH pulse physiology, Mod-GRF 1-29 + Ipamorelin is preferred

With DAC (chronic dosing)#

Multiple weekly injections of CJC-1295 with DAC (tested in humans at 30–60 µg/kg/week):

• GH: sustained elevation throughout treatment period
• IGF-1: 20–55% elevation above baseline, maintained throughout
• Safety: no significant adverse effects reported in published clinical studies

IGF-1 Elevation Data from Published Studies#

The Teichman et al. (2006) study provides the most detailed human CJC-1295 pharmacokinetic and pharmacodynamic data:

Elevation was maintained for at least 14 days in the multiple-dose groups, with no apparent tachyphylaxis in the 28-day study period.

In rodents, comparable elevations are observed, typically in the 30–60% range with weekly dosing in GH-replete animals and higher in GH-deficient models.

With DAC vs. Without DAC: Which for Your Research?#

Choose CJC-1295 without DAC (Mod-GRF 1-29) when:#

• Studying pulsatile GH dynamics
• Combining with Ipamorelin for GH pulses (standard combination)
• Research requires physiological GH pulsatility
• Protocol duration is short (1–2 weeks)
• Budget is a consideration (similar compound cost, but fewer total doses needed with DAC)

Choose CJC-1295 with DAC when:#

• Sustained IGF-1 elevation is the primary endpoint (not GH pulse dynamics)
• Simplifying the dosing schedule (1×/week vs. 2–3×/day)
• Chronic 4–12 week protocols where once-weekly dosing reduces animal stress
• Studying the effects of sustained (non-pulsatile) GH exposure specifically

The non-DAC form is more physiological#

For most research aiming to model or stimulate the endogenous GH axis, Mod-GRF 1-29 (CJC-1295 without DAC) + Ipamorelin is the physiologically closer approximation. The DAC form is a pharmacological tool for creating sustained GHRH stimulation — useful for specific endpoints but not a closer model of endogenous GH pulsation.

Protocol Design#

CJC-1295 without DAC + Ipamorelin (standard)#

CJC-1295 with DAC (long-acting protocol)#

Combination with Ipamorelin#

The Ipamorelin + CJC-1295 combination is covered in detail in our dedicated stack article. Key points:

• Co-administration produces synergistic GH release (3–10× monotherapy)
• CJC-1295 provides GHRH-R activation; Ipamorelin provides GHS-R1a activation + somatostatin suppression
• Combined IGF-1 elevation exceeds either compound alone
• Co-injection at the same session (same time, different syringes or mixed) is the standard protocol

Frequently Asked Questions#

Is CJC-1295 with or without DAC the same as Mod-GRF 1-29? "Mod-GRF 1-29" and "CJC-1295 without DAC" are the same compound. Both refer to the 29-amino-acid GHRH analog with the four stabilizing substitutions. "CJC-1295 with DAC" is a different compound — it adds the maleimide-albumin binding modification.

Why does CJC-1295 with DAC last 8 days? The DAC linker covalently binds albumin (half-life 19 days). The CJC-1295-albumin conjugate is large (≈70 kDa), above the renal filtration cutoff. Slow hydrolysis of the CJC-1295 from the albumin depot releases active peptide over 6–8 days.

Can CJC-1295 cause GH axis desensitization? Continuous GHRH-R stimulation (as with CJC-1295 with DAC) can produce partial tachyphylaxis over weeks. This is observed with all forms of sustained GHRH-R activation. Pulsatile protocols (Mod-GRF without DAC) minimize this risk by allowing receptor recovery between doses.

What is the difference between CJC-1295 and Sermorelin? Sermorelin is the full GRF(1-29) sequence (native sequence, 29 amino acids, no substitutions). It has a ~10 minute half-life. CJC-1295 without DAC (Mod-GRF 1-29) is the same length but has four amino acid substitutions that extend the half-life to 30–60 minutes. Sermorelin is the older, less stable compound; Mod-GRF is the improved research standard.

Is there a maximum effective dose of CJC-1295 with DAC? Published human data shows a dose-response plateau around 120–240 µg/kg SC — doses beyond this do not produce proportionally greater IGF-1 elevation, suggesting GHRH-R saturation or maximal pituitary GH output has been reached.

Key References#

1. Teichman SL, et al. (2006). "Prolonged stimulation of growth hormone release in humans by CJC-1295, a long-acting analog of growth hormone-releasing hormone." Journal of Clinical Endocrinology & Metabolism, 91(3):799–805.

2. Bowers CY. (1998). "Growth hormone-releasing peptide (GHRP)." Cellular and Molecular Life Sciences, 54(12):1316–1329.

3. Frohman LA, Jansson JO. (1986). "Growth hormone-releasing hormone." Endocrine Reviews, 7(3):223–253.

4. Raun K, et al. (1998). "Ipamorelin, the first selective growth hormone secretagogue." European Journal of Endocrinology, 139(5):552–561.

5. Svensson J, et al. (2000). "Effects of GHRP-2 and GHRH on GH secretion." Journal of Clinical Endocrinology and Metabolism, 85(11):4221.

Research Use Only: CJC-1295 and all products referenced are sold exclusively for in-vitro research and laboratory use. Not for human consumption. JuicedPharma does not provide medical advice.

Published by JuicedPharma Research Team · September 2026 · Category: Growth Hormone