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Growth Hormone Secretagogues
Half-life: ~30 minutes (without DAC) | ~6-8 days (with DAC)
Last updated: July 22, 2026

CJC-1295

CJC-1295 (Modified GRF 1-29, Tetrasubstituted GHRH 1-29)

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CJC-1295 is a synthetic analog of growth hormone-releasing hormone (GHRH) that stimulates the pituitary gland to release growth hormone through activation of the GHRH receptor. Developed by ConjuChem Biotechnologies, this 29-amino acid peptide features four amino acid substitutions at positions 2, 8, 15, and 27 that dramatically enhance its resistance to enzymatic degradation compared to native GHRH. The tetrasubstituted structure extends plasma half-life from minutes to approximately 30 minutes for the standard form, and when conjugated with Drug Affinity Complex (DAC), the half-life extends to approximately 6-8 days by binding to serum albumin. CJC-1295 has been extensively studied in clinical trials for growth hormone deficiency, lipodystrophy, and age-related decline in GH levels. Unlike direct GH administration, CJC-1295 preserves the body's natural pulsatile GH secretion pattern, maintaining feedback regulation and potentially offering a more physiological approach to GH optimization.
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Table of Contents

What is CJC-1295?

CJC-1295 is a synthetic peptide analog of growth hormone-releasing hormone (GHRH), the hypothalamic hormone that signals the pituitary gland to synthesize and secrete growth hormone. Developed by ConjuChem Biotechnologies in the early 2000s, CJC-1295 represents a significant advancement in GHRH analog design, featuring modifications that dramatically extend its biological activity compared to native GHRH.

29Amino Acids
30 minHalf-life (no DAC)
6-8 daysHalf-life (with DAC)
Phase IIClinical Trials

Native GHRH has an extremely short plasma half-life of approximately 7 minutes due to rapid enzymatic degradation, making it impractical for therapeutic use. CJC-1295 addresses this limitation through four strategic amino acid substitutions (tetrasubstitution) at positions 2, 8, 15, and 27 that protect the peptide from dipeptidyl peptidase IV (DPP-IV) cleavage and other proteolytic enzymes. These modifications extend the half-life to approximately 30 minutes while maintaining full biological activity at the GHRH receptor.

ℹ️ Two Forms of CJC-1295: CJC-1295 is available in two distinct forms: CJC-1295 without DAC (also called Modified GRF 1-29 or Mod GRF) and CJC-1295 with DAC (Drug Affinity Complex). The DAC version includes a lysine linker that binds to serum albumin, extending half-life to 6-8 days. Each form has distinct dosing protocols and pharmacokinetic profiles.

The compound underwent clinical development for conditions including adult growth hormone deficiency and HIV-associated lipodystrophy. Phase II trials demonstrated significant, dose-dependent increases in both growth hormone and IGF-1 levels, with effects lasting considerably longer than endogenous GHRH. While clinical development was eventually discontinued, the extensive human data generated provides valuable insights into CJC-1295's pharmacology.

What distinguishes CJC-1295 from exogenous growth hormone administration is its mechanism of action. Rather than replacing the body's GH production, CJC-1295 stimulates the pituitary to release its own growth hormone, preserving the natural pulsatile secretion pattern that appears important for optimal physiological effects. This approach maintains the body's feedback regulation systems, potentially offering advantages for long-term use.

Research Benefits

Stimulates natural growth hormone release from the pituitary

Preserves physiological pulsatile GH secretion patterns

Enhanced stability compared to native GHRH (30-60 min half-life)

DAC version provides extended duration (6-8 day half-life)

Maintains negative feedback regulation unlike exogenous GH

Synergistic effects when combined with GHRP peptides

Promotes lean body mass and improved body composition

Supports deep sleep and recovery through GH optimization

How CJC-1295 Works

CJC-1295 exerts its effects by binding to and activating GHRH receptors (GHRH-R) on somatotroph cells in the anterior pituitary gland. This receptor is a G-protein coupled receptor (GPCR) that, when activated, triggers a cascade of intracellular signaling events leading to growth hormone synthesis and release.

Mechanism of GHRH Receptor Activation

Upon binding to GHRH-R, CJC-1295 activates the Gs protein, which stimulates adenylyl cyclase to increase intracellular cyclic AMP (cAMP) levels. Elevated cAMP activates protein kinase A (PKA), which phosphorylates various cellular targets including CREB (cAMP response element-binding protein). This leads to both acute GH release from secretory vesicles and increased transcription of the GH gene for sustained hormone production.

🧬

GHRH Receptor Agonism

Binds and activates pituitary GHRH receptors, stimulating growth hormone synthesis and secretion.

⏱️

Extended Half-Life

Tetrasubstitution protects against enzymatic degradation, extending activity from minutes to hours.

📈

Pulsatile GH Release

Preserves natural GH pulsatility unlike continuous exogenous GH administration.

🔄

Feedback Regulation

Maintains hypothalamic-pituitary feedback loops, preventing excessive GH levels.

DAC Conjugation Technology

The Drug Affinity Complex (DAC) version of CJC-1295 employs a maleimidopropionic acid linker attached to a lysine residue that forms a covalent bond with serum albumin following injection. Since albumin has a circulating half-life of approximately 20 days, this "bioconjugation" approach dramatically extends the peptide's presence in circulation. The bound peptide maintains activity and gradually releases as albumin turns over.

📝 Note: The extended half-life of CJC-1295 with DAC (6-8 days) means it provides more continuous GHRH receptor stimulation rather than discrete pulses. This has implications for dosing strategy and potentially for receptor sensitivity over time.

Synergy with GHRPs

CJC-1295 is frequently combined with growth hormone-releasing peptides (GHRPs) like Ipamorelin for enhanced effects. This synergy occurs because GHRH and GHRPs work through distinct receptor systems:

  • CJC-1295 (GHRH pathway): Stimulates GH synthesis and release via GHRH receptor
  • Ipamorelin (ghrelin pathway): Amplifies GH release via GHS-R1a receptor while suppressing somatostatin

When both pathways are activated simultaneously, GH release is amplified beyond the additive effect of either alone. The GHRP component also reduces somatostatin tone—somatostatin is the hormone that normally inhibits GH release—further enhancing the combined effect.

Research Applications

Adult growth hormone deficiency

Active research area with published studies

Age-related GH decline and sarcopenia

Active research area with published studies

HIV-associated lipodystrophy

Active research area with published studies

Body composition optimization

Active research area with published studies

Sleep quality and architecture

Active research area with published studies

Metabolic health and insulin sensitivity

Active research area with published studies

Wound healing and tissue repair

Active research area with published studies

Bone density and skeletal health

Active research area with published studies

Research Findings

CJC-1295 has been evaluated in multiple clinical studies, primarily examining the DAC-conjugated formulation for its extended duration of action. The research provides valuable human pharmacokinetic and pharmacodynamic data.

Phase II Clinical Trial Results

A pivotal study published in the Journal of Clinical Endocrinology & Metabolism (2006) examined CJC-1295 DAC in healthy adults aged 21-61 years. Key findings included:

🔑 Key Clinical Trial Findings

  • Single subcutaneous doses produced dose-dependent increases in plasma GH lasting 6+ days
  • Mean IGF-1 levels increased 1.5 to 3-fold above baseline
  • GH AUC (area under curve) increased 2 to 10-fold depending on dose
  • Effects persisted for up to 14 days after single administration
  • Generally well-tolerated with injection site reactions as most common side effect

The study demonstrated that single doses of 30, 60, or 125 μg/kg produced sustained elevations in both GH and IGF-1, with the 125 μg/kg dose showing effects lasting nearly two weeks. This confirmed the extended pharmacokinetic profile enabled by the DAC bioconjugation technology.

HIV Lipodystrophy Research

CJC-1295 was evaluated in HIV patients with lipodystrophy, a metabolic condition characterized by abnormal fat distribution. Research showed:

  • Significant reductions in trunk fat accumulation
  • Decreased visceral adipose tissue
  • Maintained lean body mass
  • Improvements in metabolic parameters

These findings supported the potential use of GHRH analogs for metabolic conditions beyond simple GH deficiency.

Comparative Research: CJC-1295 vs. Other GHRH Analogs

Studies comparing CJC-1295 to other GHRH analogs like sermorelin demonstrated superior pharmacokinetic properties:

CompoundHalf-LifeDosing FrequencyGH Response Duration
Native GHRH~7 minutesNot practicalMinutes
Sermorelin10-20 minutes1-2x daily1-2 hours
CJC-1295 (no DAC)~30 minutes2-3x daily3-4 hours
CJC-1295 (with DAC)6-8 days1-2x weekly6-14 days
Tesamorelin~38 minutesOnce dailyHours

Body Composition Research

Research examining CJC-1295's effects on body composition showed promising results. Studies in both healthy volunteers and clinical populations demonstrated:

  • Increases in lean body mass proportional to GH/IGF-1 elevation
  • Reductions in body fat percentage, particularly visceral fat
  • Improved nitrogen retention suggesting enhanced protein synthesis
  • Enhanced lipolytic activity consistent with elevated GH
✓ Research Highlight: The ability of CJC-1295 to elevate both GH and IGF-1 while preserving pulsatile secretion patterns suggests potential advantages over exogenous GH for body composition optimization.
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Dosage & Administration

Dosing protocols for CJC-1295 differ significantly based on whether the DAC or non-DAC version is being used, reflecting their vastly different pharmacokinetic profiles. The following represents dosing information from research literature—not recommendations for human use.

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

Due to its approximately 30-minute half-life, CJC-1295 without DAC requires more frequent administration to maintain effective GH stimulation:

ProtocolDoseFrequencyTiming
Conservative100 mcg2x dailyAM fasted, before bed
Standard100 mcg3x dailyAM, post-workout, bedtime
Intensive100-200 mcg3x dailyWith Ipamorelin
ℹ️ Timing Matters: For CJC-1295 without DAC, administration should occur on an empty stomach or at least 1-2 hours after eating. Elevated blood glucose and fatty acids can significantly blunt the GH response. The bedtime dose is particularly valuable as it enhances the natural nocturnal GH surge.

CJC-1295 With DAC

The extended half-life of the DAC version allows for once or twice weekly dosing:

ProtocolDoseFrequencyNotes
Standard1-2 mgOnce weeklyProvides baseline elevation
Moderate1 mgTwice weeklyMore consistent levels
Clinical Trial Range30-125 mcg/kgWeeklyDose-dependent response

Reconstitution Guidelines

1

Gather Materials

Obtain bacteriostatic water, alcohol swabs, and insulin syringes (29-31 gauge).

2

Calculate Volume

For a 2mg vial, adding 2ml bacteriostatic water yields 1mg/ml (1000mcg/ml). Each 0.1ml = 100mcg.

3

Reconstitute Gently

Direct water stream against vial wall, not directly onto powder. Let dissolve—do not shake.

4

Storage

Store reconstituted solution at 2-8°C (refrigerator). Use within 3-4 weeks.

Combination Protocols with Ipamorelin

When combined with Ipamorelin (the most common research stack), protocols typically use:

  • CJC-1295 without DAC: 100mcg combined with Ipamorelin 100-200mcg
  • Administered 2-3 times daily in the same injection
  • Synergistic effect amplifies GH release beyond either alone
  • Most common timing: morning fasted, post-workout, and 30 minutes before bed

Pro Tip

The bedtime dose is considered most important by many researchers, as it amplifies the natural nocturnal GH pulse that occurs during slow-wave (deep) sleep. This pulse is responsible for much of GH's recovery and regenerative effects.

Work out your CJC-1295 draw in units

Enter the vial size, the bacteriostatic water you add and the dose you want, and the calculator gives the syringe units, how long the vial lasts and when to discard it.

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Safety & Side Effects

Clinical trial data for CJC-1295 demonstrated a generally favorable safety profile, though the compound never completed full Phase III development. Understanding both observed and theoretical safety considerations is essential for researchers.

Observed Side Effects in Clinical Trials

The most commonly reported adverse events in human trials included:

💉

Injection Site Reactions

Redness, swelling, or itching at injection site—typically mild and transient.

🔥

Flushing

Warmth and redness, particularly facial, occurring shortly after injection.

😵

Dizziness/Lightheadedness

Transient, typically resolving within minutes to an hour.

🤕

Headache

Reported in some subjects, usually mild and short-lived.

⚠️ Warning: In 2006, one death occurred during CJC-1295 clinical trials, leading to program suspension. Investigation attributed the death to a pre-existing cardiac condition unrelated to the peptide, but this event contributed to discontinuation of clinical development.

Potential Concerns with Elevated GH/IGF-1

Any compound that elevates growth hormone and IGF-1 carries theoretical concerns related to these hormones' effects:

  • Water retention: GH can cause fluid retention and mild edema, particularly at higher doses
  • Joint discomfort: Some users report carpal tunnel-like symptoms with elevated GH
  • Blood glucose effects: GH has anti-insulin effects that may affect glucose regulation
  • Theoretical cancer concerns: Elevated IGF-1 has been associated with increased cancer risk in epidemiological studies, though causation is not established

DAC vs. Non-DAC Safety Considerations

The different pharmacokinetic profiles of the two versions have safety implications:

ConsiderationWithout DACWith DAC
Receptor Desensitization RiskLower (pulsatile)Higher (continuous)
Ability to "Stop" EffectsClears in hoursPersists 1-2 weeks
Dosing PrecisionMore controlLess flexible
Mimics Natural RhythmMore closelyLess closely
📝 Cycling Considerations: To minimize potential receptor desensitization, many research protocols incorporate cycling—for example, 5 days on/2 days off, or 8 weeks on/4 weeks off. This may be particularly important with the DAC version given its extended receptor engagement.

Contraindications and Cautions

Based on mechanism of action and GH effects, theoretical contraindications include:

  • Active malignancy or history of certain cancers
  • Untreated pituitary tumors
  • Diabetic retinopathy
  • Pregnancy and breastfeeding
  • Severe cardiac conditions

Individuals with diabetes should exercise particular caution due to GH's effects on glucose metabolism. Medical supervision and monitoring are essential for any research involving human subjects.

Frequently Asked Questions

What is the difference between CJC-1295 with DAC and without DAC?
The key difference lies in half-life and dosing frequency. CJC-1295 without DAC (also called Modified GRF 1-29 or Mod GRF 1-29) has a half-life of approximately 30 minutes and requires more frequent administration, typically 2-3 times daily for optimal results. CJC-1295 with DAC (Drug Affinity Complex) features a lysine linker that allows the peptide to bind to serum albumin in the bloodstream, extending its half-life to 6-8 days. This means DAC versions can be administered just 1-2 times per week. However, the longer half-life also means DAC continuously stimulates GH release rather than mimicking natural pulsatile patterns, which some researchers believe may lead to receptor desensitization over time. Many prefer the non-DAC version precisely because its shorter action allows for more physiological GH pulses when timed appropriately.
How does CJC-1295 compare to direct growth hormone injections?
CJC-1295 and direct GH represent fundamentally different approaches to growth hormone optimization. Direct GH (somatropin) provides exogenous hormone that suppresses the body's own GH production through negative feedback, and levels remain constant rather than pulsatile. CJC-1295, as a GHRH analog, stimulates the pituitary to release its own GH, preserving the natural pulsatile secretion pattern that appears important for optimal effects while maintaining feedback regulation. Research suggests pulsatile GH release may be superior for certain outcomes like fat metabolism and tissue repair. CJC-1295 also stimulates endogenous IGF-1 production through the natural pathway. However, direct GH provides more predictable dosing and may be necessary when the pituitary cannot respond adequately to secretagogue stimulation. The choice depends on individual goals, physiology, and whether preserving natural regulation is prioritized.
Why is CJC-1295 often combined with Ipamorelin?
CJC-1295 and Ipamorelin work through complementary mechanisms that create synergistic effects when combined. CJC-1295 is a GHRH analog that acts on GHRH receptors on somatotroph cells in the pituitary, essentially telling these cells to produce and release growth hormone. Ipamorelin is a ghrelin mimetic (GHRP) that acts on GHS-R1a receptors, amplifying the GH release signal through a separate pathway while also suppressing somatostatin, which normally inhibits GH release. When combined, you get stimulation through two distinct receptor systems plus reduced inhibitory signaling—resulting in GH release significantly greater than either peptide alone. Studies have shown this combination produces more robust and sustained GH pulses. Additionally, Ipamorelin is considered one of the cleanest GHRPs with minimal effects on cortisol, prolactin, or appetite, making it an ideal pairing partner for CJC-1295.
What were the results of CJC-1295 clinical trials?
CJC-1295 underwent several clinical trials, primarily examining the DAC-conjugated version. A key Phase II trial in healthy adults aged 21-61 showed that single doses of CJC-1295 DAC produced dose-dependent increases in plasma GH and IGF-1 levels lasting 6-14 days after injection. Mean IGF-1 levels increased by 1.5 to 3-fold above baseline depending on dose. A trial in HIV-associated lipodystrophy patients showed improvements in trunk fat and visceral adiposity. Studies demonstrated the peptide was generally well-tolerated, with injection site reactions and transient flushing being the most common adverse events. However, ConjuChem's clinical development program was discontinued in 2006 following a death in one trial, though this was later attributed to a pre-existing cardiac condition rather than the peptide. The clinical data that exists supports CJC-1295's ability to robustly stimulate GH and IGF-1 in humans, though full Phase III trials were never completed.
What is the optimal timing for CJC-1295 administration?
Optimal timing depends on whether you're using the DAC or non-DAC version. For CJC-1295 without DAC (Mod GRF 1-29), timing is crucial because of its short 30-minute half-life. Most protocols suggest administration 2-3 times daily, with key timing points being: first thing in the morning on an empty stomach, post-workout, and before bed. The bedtime dose is particularly important as it can amplify the natural nocturnal GH surge that occurs during deep sleep. Doses should be taken at least 1-2 hours away from meals, especially those containing fats and carbohydrates, as elevated blood sugar and fatty acids can blunt the GH response. For CJC-1295 with DAC, timing is less critical due to the extended half-life—dosing 1-2 times per week provides sustained elevation. However, some still prefer evening administration to augment sleep-related GH release.
Does CJC-1295 affect cortisol or other hormones?
One of CJC-1295's advantages compared to some other GH secretagogues is its relatively selective action on growth hormone release. Unlike GHRP-6 and to a lesser extent GHRP-2, CJC-1295 does not significantly stimulate cortisol, prolactin, or ACTH at normal doses. This is because CJC-1295 acts specifically through the GHRH receptor pathway rather than the ghrelin/GHS-R pathway that can influence other hormonal axes. Clinical trial data showed no meaningful changes in cortisol, prolactin, TSH, LH, or FSH with CJC-1295 administration. However, the resulting increase in GH and IGF-1 can have downstream effects on other systems—IGF-1 may influence insulin sensitivity, and elevated GH can affect thyroid hormone conversion (T4 to T3). These secondary effects are generally considered mild at typical research doses but should be monitored in longer-term use.
Can CJC-1295 cause pituitary desensitization?
This is a debated topic in the research community, with some important distinctions between the two forms. CJC-1295 with DAC, due to its continuous presence in the bloodstream over 6-8 days, theoretically poses a higher risk of GHRH receptor desensitization compared to the pulsatile stimulation achieved with the non-DAC version. Continuous receptor stimulation can lead to downregulation, potentially reducing effectiveness over time. However, clinical trials up to 12 weeks did not show evidence of tachyphylaxis (diminishing response). CJC-1295 without DAC, by virtue of its shorter half-life, allows for receptor recovery between doses and more closely mimics natural GHRH pulsatility, theoretically reducing desensitization risk. Many research protocols incorporate cycling—such as 5 days on, 2 days off, or 8 weeks on, 4 weeks off—to maintain receptor sensitivity. Combining with a GHRP like Ipamorelin may also help prevent desensitization by providing dual-pathway stimulation.
What are the differences between CJC-1295, Sermorelin, and Tesamorelin?
All three are GHRH analogs that stimulate pituitary GH release, but they differ in structure, stability, and clinical status. Sermorelin is the shortest, containing GHRH amino acids 1-29 with minimal modifications, resulting in a very short half-life of just 10-20 minutes. It's FDA-approved for GH deficiency diagnosis but requires frequent dosing. CJC-1295 (without DAC) contains the same 1-29 sequence but with four amino acid substitutions (tetrasubstitution) that extend half-life to about 30 minutes—still requiring multiple daily doses but more practical than sermorelin. Tesamorelin is a 44-amino acid GHRH analog with a trans-3-hexenoic acid modification, FDA-approved specifically for HIV-associated lipodystrophy. It has a half-life of about 38 minutes and has the most clinical data supporting efficacy and safety. CJC-1295 with DAC has the longest half-life of 6-8 days due to albumin binding but never completed FDA approval. In terms of potency per dose, studies suggest all are roughly comparable when adjusted for their different dosing frequencies.

Scientific References

1

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

Journal of Clinical Endocrinology & Metabolism (2006)

2

A Synthetic Long-Acting Agonist of Growth Hormone-Releasing Hormone, CJC-1295, for Treatment of Lipodystrophy

ClinicalTrials.gov (2003)

3

Extended release growth hormone-releasing hormone analogs: Structural optimization and biological studies

Bioconjugate Chemistry (2006)

4

Growth hormone-releasing hormone analogs: chemistry and pharmacology

Endocrine Reviews (2008)

5

The growth hormone secretagogue MK-677 and its peptide analogs: biological effects and clinical applications

Endocrine Reviews (1997)

6

GH-releasing peptides and GH secretagogues: basic findings and clinical implications

Growth Hormone & IGF Research (2001)

7

Effects of recombinant human growth hormone-releasing hormone and growth hormone on lipolysis and glucose metabolism in HIV-infected patients with fat accumulation

Journal of Clinical Endocrinology & Metabolism (2004)

8

Physiological aspects of the GH/IGF-I axis in skeletal muscle

Endocrine Reviews (2015)

Quick Reference

Molecular Weight3,367.97 Da (CJC-1295 without DAC)
Half-Life~30 minutes (without DAC) | ~6-8 days (with DAC)
Purity≥99%
FormLyophilized powder (white to off-white)
SupplierAscension Peptides

Sequence

Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2

Storage

Lyophilized: -20°C for long-term | Reconstituted: 2-8°C, use within 21 days

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