Side-by-side · Research reference
CJC-1295 (no DAC)vsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 1HUMAN-REVIEWED15/51 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
CJC-1295 (no DAC)
Short-acting GHRH · No DAC variant
SQ · Pre-sleep · 1–2×/day
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
CJC-1295 (no DAC)
PE 22-28
Primary target
Pituitary GHRH receptorTeichman 2006
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisTeichman 2006
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Pulsatile GH release matching physiological pattern; subsequent IGF-1 elevationIonescu 2006
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
Yes — short pulse preserves somatostatin negative feedbackIonescu 2006
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Modified human GRF 1-29 with four substitutions (D-Ala²/Gln⁸/Ala¹⁵/Leu²⁷) for protease resistanceTeichman 2006
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
Not reported in short-term studies
Not reported in animal studies
02Dosage Protocols
Parameter
CJC-1295 (no DAC)
PE 22-28
Frequency
1–2× daily (pre-sleep ± morning)
Once daily
Sustained antidepressant effect over 7+ days.
Lower / starter dose
50 mcg per dose
—
Evidence basis
Phase 1 (CJC-1295 with DAC); analog dataTeichman 2006Ionescu 2006
No-DAC variant is less studied directly; PK extrapolated from native GHRH.
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Duration
8–12 weeks on / 4 off (anecdotal)
—
Reconstitution
Bacteriostatic water
—
Timing
Pre-sleep + fasted preferred
—
Half-life
~30 minIonescu 2006
Short pulse vs CJC-1295-DAC (~8 days). Choose no-DAC for pulsatile, DAC for sustained.
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
04Side Effects & Safety
Parameter
CJC-1295 (no DAC)
PE 22-28
Injection site reaction
Erythema, mild pruritus
—
Flushing / headache
Common transient effect
—
Cortisol elevation
Minimal at standard doses
—
Prolactin elevation
Minimal
—
Glucose intolerance
Possible at high cumulative doses
—
IGF-1 elevation
Dose-dependent; monitor with chronic use
—
Cancer risk
Contraindicated in active malignancy (GH/IGF-1 axis)
—
Pregnancy / OB
Avoid
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
CJC-1295 (no DAC)
- ·Active malignancy or cancer history
- ·Pregnancy / breastfeeding
- ·Disrupted hypothalamic-pituitary axis
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
CJC-1295 (no DAC)
- ·Untreated diabetes
- ·Severe insulin resistance
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
CJC-1295 (no DAC)
PE 22-28
1. Reconstitution
Add 2 mL bacteriostatic water to 2 mg vial → 1 mg/mL = 100 mcg per 0.1 mL. Roll gently.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Injection site
Subcutaneous, abdomen or thigh. Rotate sites.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Timing
Pre-sleep preferred. Often combined with ipamorelin in the same syringe.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Storage
Lyophilised: room temp, protected from light. Reconstituted: refrigerate 2–8 °C, use within 30 days.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
5. Needle
29–31G, 4–8 mm insulin syringe.
—
06Stack Synergy
CJC-1295 (no DAC)
+ Ipamorelin
StrongCJC-1295 (no DAC) and ipamorelin are the canonical "GHRH + GHRP" dual-axis stack at physiological timing. Both peak within 30 min and clear within 2 hours, producing a sharp, high-amplitude GH pulse closely resembling natural physiology. Preferred over the CJC-1295-DAC + ipamorelin stack when pulsatility (vs sustained elevation) is the goal.
- CJC-1295 (no DAC)
- 100 mcg SQ · pre-sleep
- Ipamorelin
- 200–300 mcg SQ · same injection
- Primary benefit
- Pulsatile GH stimulation, recovery, body composition
PE 22-28
— no documented stacks