CJC-1295 (GHRH Analog — DAC & No-DAC)
CJC-1295 is a synthetic analog of growth hormone-releasing hormone (GHRH), available in two formulations: with Drug Affinity Complex (DAC) for extended 6–8 day half-life enabling weekly dosing, and without DAC (Modified GRF 1-29) for pulsatile GH release with 30-minute half-life. Both variants are studied for GH secretagogue activity, body composition, and anti-aging effects, with Grade B+ evidence from human pharmacokinetic and GH-stimulation studies.
DAC vs. No-DAC: Key Comparison
CJC-1295 with DAC
- Half-life: 6–8 days
- Dose: 2 mg per injection
- Frequency: Weekly or bi-weekly
- GH pattern: Sustained elevation ("GH bleed")
- Pro: Convenient dosing
- Con: Blunts natural GH pulse architecture
CJC-1295 no DAC (Mod GRF 1-29)
- Half-life: ~30 minutes
- Dose: 100–300 mcg per injection
- Frequency: 2–3x daily
- GH pattern: Pulsatile (physiologic)
- Pro: Preserves GH receptor sensitivity
- Con: Multiple daily injections required
Mechanism of Action
CJC-1295 acts as a GHRH receptor (GHRHR) agonist at the anterior pituitary. Native GHRH is a 44-amino-acid peptide with a very short plasma half-life (~7 minutes) due to DPP-4 cleavage. CJC-1295 incorporates four amino acid substitutions that protect against DPP-4 and endopeptidase degradation, extending its half-life to 30 minutes (no DAC) or ~8 days (DAC variant).
The DAC modification involves a maleimide group on lysine 30 that covalently and irreversibly binds to free cysteine residues on albumin in vivo — essentially piggybacking on albumin's long half-life for sustained circulation. This is the same "drug affinity complex" technology used in some therapeutic antibody conjugates.
Upon GHRHR binding, CJC-1295 stimulates pituitary somatotroph cells via Gs-cAMP-PKA signaling, increasing GH synthesis and secretion. Unlike GHRP/GHSR agonists (e.g., Ipamorelin), GHRH analogs do not directly trigger GH release — they prime the pituitary for enhanced response. This makes the CJC-1295 + Ipamorelin combination mechanistically synergistic: GHRH priming + GHSR triggering produces GH pulses far exceeding either compound alone.
Research Protocol B+
CJC-1295 no DAC + Ipamorelin (Preferred Stack)
| Parameter | Beginner | Intermediate | Advanced |
|---|---|---|---|
| CJC-1295 (no DAC) | 100 mcg | 200 mcg | 300 mcg |
| Ipamorelin | 100 mcg | 200 mcg | 300 mcg |
| Frequency | Once daily | Twice daily | 2–3x daily |
| Timing | Pre-sleep | AM fasted + pre-sleep | AM + pre-workout + pre-sleep |
| Route | SubQ | SubQ | SubQ |
| Cycle Length | 8 weeks | 12 weeks | 16–24 weeks |
CJC-1295 with DAC (standalone)
| Parameter | Standard |
|---|---|
| Dose | 2 mg |
| Frequency | Once weekly or every 2 weeks |
| Route | SubQ |
Reconstitution Quick-Calc
Side Effects & Safety
- Water retention / mild edema (especially with DAC variant)
- Tingling or numbness in extremities (elevated GH effect)
- Injection site irritation or redness
- Fatigue or lethargy at higher doses
- Potential for elevated IGF-1 (monitor in long-term use)
- Carpal tunnel syndrome (at chronically elevated GH levels)
- No hormonal suppression of HPG axis; no PCT required
Contraindications
- Active malignancy — GH axis stimulation is contraindicated
- Acromegaly or existing growth hormone excess
- Pregnancy and breastfeeding: no safety data
Clinical Evidence
First clinical PK/PD study of CJC-1295 in 65 healthy adults. Single doses of 30–60 mcg/kg produced 2–10x increases in mean GH levels, lasting for 6 days. IGF-1 elevated 1.3–1.9x. Excellent tolerability.
Reviews the physiological importance of pulsatile GH release and provides mechanistic context for preferring no-DAC pulsatile protocols over sustained GH elevation for long-term receptor sensitivity.
Comprehensive review of GHRH analogs and GHSR agonists, including CJC-1295 combination data, establishing the mechanistic rationale for GHRH + GHSR synergy in GH pulse amplification.
Stacking Recommendations
| Stack Partner | Synergy | Protocol Note |
|---|---|---|
| Ipamorelin | GHRH priming + GHSR trigger = synergistic GH pulse amplitude | Equal mcg doses, inject simultaneously pre-sleep |
| Sermorelin | Alternative GHRH analog; lower potency but milder side effect profile | May substitute CJC no DAC for milder protocols |
| MK-677 | Oral GHSR agonist as daytime complement to injectable CJC+Ipa pre-sleep | MK-677 10–25 mg AM + CJC+Ipa pre-sleep |
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