CJC-1295 NO DAC
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Modified GRF(1-29), a GHRH analog that stimulates pulsatile growth hormone release from the anterior pituitary while preserving physiological feedback regulation.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | Mod-GRF(1-29), Modified GRF(1-29), CJC-1295 without DAC, Tetrasubstituted GRF(1-29) |
| Category | GH Axis / Muscle Growth / Anti-Aging / Recovery |
| 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 (29 aa, 4 substitutions for protease resistance) |
| Molecular Weight | ~3367 Da |
| Molecular Formula | C152H252N44O42 |
| PubChem CID | 91976842 |
| Administration | SubQ |
| Typical Dose Range | 100-200 mcg per injection (from literature) |
| Half-Life | ~30 minutes (NO DAC version; preserves pulsatile GH secretion) |
| Storage | Lyophilized: -20C for 1-2 years; Reconstituted: 2-8C, use within 2-4 weeks |
| FDA Status | Research only. Not approved for any indication. CJC-1295 with DAC reached Phase II clinical trials but development was halted. |
| WADA Status | Prohibited (S2 – Peptide Hormones, Growth Factors, Related Substances) |
Mechanism of Action
CJC-1295 NO DAC (Mod-GRF 1-29) is a synthetic analog of the first 29 amino acids of endogenous growth hormone-releasing hormone (GHRH), modified at four positions (Ala2, Ala8, Ala15, Leu27 substitutions) to confer resistance to dipeptidyl peptidase IV (DPP-IV) cleavage and enzymatic degradation. These substitutions extend the functional half-life from approximately 7 minutes (native GHRH) to approximately 30 minutes while maintaining the short-acting pharmacokinetic profile critical for preserving pulsatile GH secretion (PMID 15817669).
The peptide binds to GHRH receptors on anterior pituitary somatotrophs, stimulating both synthesis and pulsatile release of growth hormone (GH1, UniProt P01241). Unlike CJC-1295 with DAC (Drug Affinity Complex), which conjugates to albumin for a half-life of approximately 6-8 days and produces sustained "tonic" GH elevation, the NO DAC variant produces discrete GH pulses that mirror endogenous physiology. This pulsatile pattern is essential because continuous GH elevation downregulates GH receptors and induces insulin resistance, while pulsatile release maintains receptor sensitivity and normal metabolic signaling (PMID 17018654).
The critical pharmacological feature of CJC-1295 NO DAC is its synergy with ghrelin receptor agonists (GHSR/GHS-R1a, UniProt Q92847) such as Ipamorelin. Because GHRH and ghrelin act on different receptor systems to stimulate GH release from somatotrophs, co-administration produces a supra-additive GH pulse — reported at 7-10x greater amplitude than either agent alone. The short half-life also preserves normal somatostatin negative feedback, preventing GH axis suppression during chronic use (PMID 16352683).
Downstream, the GH pulses stimulate hepatic IGF-1 synthesis, activating anabolic and tissue repair signaling cascades throughout the body. This GH-IGF-1 axis activation supports lean mass accretion, fat oxidation, connective tissue repair, and sleep architecture improvement.
Key Research Areas
- GH-IGF-1 axis optimization – Prolonged stimulation of pulsatile GH and IGF-1 secretion in human subjects with single and multiple doses
- Growth normalization – CJC-1295 restores normal growth patterns in GHRH knockout mouse models
- Somatopause management – Age-related GH decline reversal via pituitary stimulation
- Body composition – GH-mediated lipolysis and lean mass accretion
- Anti-doping detection – Extensive work on immunoassay and mass spectrometry methods for GHRH analog detection
- Sports medicine – Emerging interest in peptide therapies for musculoskeletal recovery and performance
- Synergistic GH secretion – Combined GHRH + GHRP protocols for amplified GH release
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 1 | Single-dose and multi-dose PK/PD in healthy volunteers |
| Human observational | 1 | Netnography of female use patterns |
| Animal in vivo | 2 | GHRH knockout mice, serum protein changes |
| In vitro | 2 | Detection methodology studies |
| Systematic reviews | 0 | — |
| Narrative reviews | 3 | Anti-doping, sports medicine, body composition |
Clinical Applications
- Fat Loss — GH-mediated lipolysis via pulsatile GH release
- Sarcopenia — Lean mass preservation and accretion through GH-IGF-1 signaling
- Injury Recovery — IGF-1-driven tissue repair and connective tissue remodeling
- Sleep Disorders — Amplification of natural slow-wave sleep GH pulse
Protocols Using This Peptide
Ageless Peps Products
- AP-CJC1295-Vial — CJC-1295 NO DAC Vial, $84 (WC 670)
- AP-CJC-Ipam-Blend — CJC-1295 NO DAC / Ipamorelin Blend, $64 (WC 780)
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| SubQ | 100 mcg (with GHRP) | 1-3x daily, fasted | 8-12 weeks on / 4 weeks off | PMID 17018654; practitioner consensus |
| SubQ | 100-200 mcg (standalone) | 1-3x daily, fasted | 8-12 weeks | Less effective than combination |
Cycling
Standard cycling: 5 days on / 2 days off; 8-12 weeks on / 4 weeks off. MUST be administered in a fasted state (minimum 2 hours post-meal; food blunts GH response). Pre-sleep dosing is optimal to amplify the natural slow-wave sleep GH pulse. Fasting insulin and IGF-1 levels should be monitored periodically.
Contraindications & Safety
- Contraindications: Active malignancy (GH/IGF-1 can stimulate tumor growth); acromegaly; diabetic retinopathy (IGF-1 elevation risk); active pituitary tumors
- Common side effects: Transient fluid retention, head rush at injection, injection site reactions, carpal tunnel symptoms at high doses
- Drug interactions: Insulin and oral hypoglycemics (GH can antagonize insulin sensitivity at supraphysiologic levels); glucocorticoids (GH effects may be blunted); somatostatin analogs (octreotide, etc. will block GH release)
- Pregnancy/nursing: Contraindicated; no safety data
- Special populations: Caution in diabetics (monitor glucose); renal/hepatic impairment data lacking; not studied in pediatrics outside of growth disorders
Cancer Considerations
CAUTION — IGF-1 axis cancer risk. GH secretagogues raise IGF-1 levels. The Lancet meta-analysis associates elevated IGF-1 with prostate cancer (OR 1.49) and premenopausal breast cancer (OR 1.65) (PMID-15110491). However, the largest observational study (15,809 GH-treated adults) found cancer incidence comparable to the general population (SIR 0.92) (PMID-35368070). Expert consensus states "no association with cancer recurrence" (PMID-35319491). Action: Contraindicated in active malignancy. Use with caution in cancer survivors; require oncologist clearance and IGF-1 monitoring.
Synergistic Combinations
- Ipamorelin + CJC-1295 NO DAC — Primary benchmark combination; 7-10x supra-additive GH pulse via dual receptor activation (GHRH-R + GHS-R1a)
- Tesamorelin — Alternative GHRH analog; FDA-approved for HIV lipodystrophy, may be substituted in clinical settings
- BPC-157 + CJC-1295 NO DAC — Tissue repair + GH-mediated anabolic support
- AOD-9604 + CJC-1295 NO DAC — GH axis + direct lipolysis for body composition
- TB-500 + CJC-1295 NO DAC — Recovery stack with complementary repair mechanisms
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| PMID-15817669 – CJC-1295 Discovery and Identification | Discovery and identification of CJC-1295 | 2005 | Preclinical |
| PMID-17018654 – CJC-1295 Pulsatile GH Secretion in Humans | CJC-1295 pulsatile GH secretion in humans | 2006 | Human PK/PD |
| PMID-16352683 – Prolonged stimulation of growth hormone (GH) and insulin-lik | Prolonged stimulation of GH and IGF-1 secretion by CJC-1295 | 2006 | Human RCT |
| PMID-16822960 – CJC-1295 Normalizes Growth in GHRH Knockout Mice | CJC-1295 normalizes growth in GHRH knockout mice | 2006 | Animal in vivo |
| PMID-19386527 – CJC-1295 GH-IGF-1 Axis Serum Protein Changes | CJC-1295 GH-IGF-1 axis serum protein changes | 2009 | Animal in vivo |
| PMID-26771670 – Netnography of Female Use of the Synthetic Growth Hormone CJ | Netnography of female use of CJC-1295 | 2016 | Observational |
| PMID-30489688 – An immuno polymerase chain reaction screen for the detection | Immuno-PCR screen for CJC-1295 and GHRH analog detection | 2018 | In vitro |
| PMID-34665524 – Advances in the detection of growth hormone releasing hormon | Advances in GHRH synthetic analog detection | 2021 | In vitro |
| PMID-41966639 – Peptide Therapies for Musculoskeletal and Athletic Performance | Peptide therapies for musculoskeletal and athletic performance | 2024 | Review |
| PMID-32257855 – Growth Hormone Secretagogues in Body Composition Management | Growth hormone secretagogues in body composition management | 2020 | Review |
| PMID-41476424 – Injectable Peptide Therapy Primer for Sports Medicine | Injectable peptide therapy primer for sports medicine | 2024 | Review |
| PMID-15110491 – IGF-1 Cancer Risk Systematic Review Meta-Analysis | IGF-1 and cancer risk: systematic review + meta-analysis (Lancet) | 2004 | Meta-Analysis |
| PMID-35319491 – GH Replacement Safety in Cancer Survivors Consensus | GH replacement safety in cancer survivors: consensus statement | 2022 | Consensus |
| PMID-35368070 – Long-term Safety of Growth Hormone in 15809 Adults | Long-term safety of growth hormone replacement in 15,809 adults | 2022 | Cohort |
References
- PMID 15817669 — Discovery and DAC technology
- PMID 17018654 — Human PK/PD data on pulsatile GH secretion
- PMID 16352683 — Prolonged GH/IGF-1 stimulation in humans
- PMID 16822960 — Growth normalization in GHRH-KO mice
- PMID 32257855 — GHS body composition review
- PMID 15110491 — Renehan AG et al. IGF-1 cancer risk: systematic review and meta-analysis. Lancet. 2004.
- PMID 35319491 — GH Replacement in Cancer Survivors Consensus Statement. 2022.
- PMID 35368070 — Long-term safety of growth hormone replacement in 15,809 adults. 2022.
Related
#peptide #gh-axis #subq