CJC-1295: the DAC vs no-DAC distinction is not a detail — it determines the entire pharmacology.
CJC-1295 is a synthetic analog of growth-hormone-releasing hormone (GHRH). The name is applied to two chemically different compounds — one with a drug-affinity complex (DAC) that binds albumin in plasma and extends half-life to approximately 7 days, and one without DAC that behaves pharmacokinetically like a conventional short GHRH analog with a half-life of 15–30 minutes. Understanding which version is under discussion is prerequisite to evaluating any claim made about CJC-1295, including the published clinical evidence.
- Two compounds share one name: CJC-1295 with DAC (long-acting, albumin-binding, ~7-day half-life) and CJC-1295 without DAC (a.k.a. Modified GRF 1-29, Mod GRF 1-29, ~15–30 min half-life).
- The published Phase II clinical trial (Teichman et al., J Clin Endocrinol Metab, 2006; PMID 16352683) used CJC-1295 with DAC. The no-DAC version has no equivalent published human Phase II data.
- CJC-1295 is a GHRH analog — it acts at the pituitary GHRH receptor (GHRH-R) to stimulate GH synthesis and secretion, not at the ghrelin receptor (GHS-R1a) like Ipamorelin or MK-677.
- The DAC version's long half-life produces sustained IGF-1 elevation and a "GH bleed" pattern rather than sharp GH pulses. Whether this sustained profile is superior to pulsatile GH release for longevity or body-composition endpoints is not established.
- Not FDA-approved. No approved indication for any version of CJC-1295. Sold under RUO framing by research peptide vendors. Most vendors selling "CJC-1295" without specification are selling the DAC version.
- Most commonly used in combination with a GHRP (Ipamorelin is the most common pairing): GHRH-R + GHS-R1a synergy produces larger GH pulses than either class alone.
GHRH biology: what CJC-1295 is acting on
Growth-hormone-releasing hormone is a 44-amino-acid neuropeptide produced in the hypothalamic arcuate nucleus. It travels via the hypophyseal portal blood to pituitary somatotrophs, where it binds the GHRH receptor (GHRH-R) — a GPCR coupled to adenylate cyclase and cAMP signalling. GHRH-R activation drives both GH synthesis (by increasing GH gene transcription) and GH secretion (by triggering somatotroph exocytosis). This is distinct from the ghrelin receptor pathway used by GHRP peptides and MK-677.
Native GHRH has a very short plasma half-life — typically 7 minutes — due to rapid cleavage by dipeptidyl peptidase IV (DPP-IV) at its N-terminal end and degradation by other serum peptidases. The first 29 residues of GHRH (GHRH[1-29]) carry full biological activity, which is why the truncated fragments used in research (Sermorelin = GHRH[1-29]; Modified GRF 1-29 = GHRH[1-29] with four amino acid substitutions) retain full GHRH-R agonism. Frohman and Kineman (Trends Endocrinol Metab, 2002; PMID 12163234) provide the foundational GHRH biology relevant to all analogs in this class.
CJC-1295 with DAC: the albumin-binding technology
CJC-1295 with DAC contains the same GHRH[1-29] backbone as Mod GRF 1-29, with the addition of a maleimidopropionate group (the DAC, drug-affinity complex) at the C-terminus lysine. This reactive group covalently binds to cysteine-34 on circulating albumin after injection. Because albumin's half-life in plasma is approximately 21 days, the DAC-bound CJC-1295 inherits extended albumin-like pharmacokinetics — measured plasma half-life approximately 6–8 days.
The clinical consequence of a 6–8 day half-life for a GH secretagogue is that weekly injections produce sustained, relatively constant IGF-1 elevation rather than the discrete GH pulses that follow injection of short-acting GHRH analogs. Ionescu and Frohman (J Clin Endocrinol Metab, 2006; PMID 16954163) showed, importantly, that pulsatile GH secretion persists even during continuous GHRH-R stimulation by CJC-1295 — a finding that matters because it means the normal pulsatile GH release pattern is not fully suppressed, only augmented.
The Teichman 2006 Phase II: what was studied and what was found
Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. "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." J Clin Endocrinol Metab. 2006;91(3):799-805. PMID 16352683.
Design: Randomized, double-blind, placebo-controlled Phase II trial in healthy adults aged 21–61 years. Subjects received single or multiple subcutaneous injections of CJC-1295 (at doses ranging from 30 to 120 mcg/kg) or placebo, with follow-up for up to 28 days per dosing cohort.
| Key finding | Result | Notes |
|---|---|---|
| Serum GH (mean peak) | 2–10-fold increase above baseline | Dose-dependent; sustained for days |
| Serum IGF-1 | +44–55% above baseline | Elevations maintained for 14–21 days after single injection |
| Duration of GH/IGF-1 elevation | 6–8 days (half-life estimate) | Confirmed the DAC albumin-binding concept |
| Tolerability | Generally well tolerated | Mild injection-site reactions; no serious adverse events reported |
| Safety signals | No significant glucose, cortisol, or prolactin changes | In contrast to MK-677 and non-selective GHRPs |
The trial is important for two reasons. First, it established that a long-acting GHRH analog can produce sustained GH/IGF-1 elevation in healthy adults without the cortisol or prolactin signals associated with GHRP-class peptides. Second, it confirmed the DAC albumin-binding mechanism works as designed in humans. What it does not establish: whether the sustained GH/IGF-1 elevation translates to better body-composition or longevity outcomes than pulsatile dosing, and what the long-term safety profile looks like beyond the trial's observation window.
Comparison: CJC-1295 DAC vs no-DAC vs Sermorelin
| Feature | CJC-1295 with DAC | CJC-1295 without DAC (Mod GRF 1-29) | Sermorelin |
|---|---|---|---|
| Plasma half-life | ~6–8 days | ~15–30 min | ~10 min |
| GH release profile | Sustained bleed (+ pulsatile) | Pulsatile (at injection) | Pulsatile (at injection) |
| Dosing frequency | 1–2× per week | Daily (pre-sleep or 2–3× daily) | Daily (pre-sleep) |
| Human Phase II data? | Yes (Teichman 2006) | No comparable study | Yes (historical FDA-approved data) |
| FDA-approved (any indication)? | No | No | Withdrawn from market 2008 (not safety) |
| Albumin binding? | Yes (DAC) | No | No |
| Research market availability | Common (often just called "CJC-1295") | Less common (often labeled Mod GRF 1-29) | Available; sometimes via 503A compounders |
The CJC-1295 + Ipamorelin stack rationale
CJC-1295 and Ipamorelin are the most commonly co-prescribed peptides in clinical anti-aging and GH-optimization research contexts, and the combination is the most widely compounded peptide stack historically available through 503A compounding pharmacies. The pharmacokinetic rationale is mechanistically clear: CJC-1295 acts at the pituitary GHRH receptor (GHRH-R), driving GH synthesis; Ipamorelin acts at the ghrelin receptor (GHS-R1a), amplifying the pituitary's GH secretory response. The two pathways are additive at the pituitary level, producing a combined GH pulse larger than either compound alone.
Ipamorelin's key advantage in this pairing is selectivity: unlike GHRP-6 or GHRP-2, it does not stimulate cortisol or prolactin release, so the GH pulse is "cleaner" with respect to off-target neuroendocrine effects. The full stack analysis — including the pharmacokinetic rationale, compounding availability history, and long-term safety gaps — is the subject of our CJC-1295 with Ipamorelin stack page (spoke 3.12).
The broader GHRH-analog family in context
CJC-1295 (DAC) sits at the long-acting end of the GHRH-analog spectrum. Sermorelin (GHRH[1-29], spoke 3.15) is the short-acting end with regulatory history. Between them, the no-DAC Modified GRF 1-29 occupies a middle position with minimal regulatory history but widely sold research-market presence. Understanding the full spectrum — including comparisons with Sermorelin — is the subject of spoke 3.16 (Sermorelin vs Ipamorelin) and the Longevity pillar overview.
At the pituitary, all GHRH analogs compete for the same GHRH-R binding site. This means stacking multiple GHRH analogs (e.g., CJC-1295 DAC + Sermorelin) is not synergistic — it would be additive at best and wasteful at worst, since the receptor can only accommodate one agonist at a time. The meaningful stack is always GHRH analog + GHRP (two different receptor systems), not GHRH analog + GHRH analog.
Pharmacokinetics and reconstitution
| Parameter | CJC-1295 with DAC | Notes |
|---|---|---|
| Route | Subcutaneous injection | IV dosing used in some Merck-era PK work; not typical |
| Plasma half-life | ~6–8 days | Albumin-binding via DAC maleimidopropionate |
| Time to peak GH | ~2–4 hours post-injection | Teichman 2006 |
| IGF-1 peak | ~2–6 days post-injection | Dependent on individual GH-axis status |
| Typical research dose | 1–2 mg per injection, 1–2× weekly | From research protocols; not a clinical recommendation |
| Reconstitution | 2 mg vial standard; use bacteriostatic water | See reconstitution guide |
| Stability (reconstituted) | 2–3 weeks refrigerated | Vendor-reported; not independently validated to pharmacopoeia standards |
Reconstitution math: a 2 mg vial with 2 mL BAC water gives 1,000 mcg/mL (1 mg/mL). 1 mg per injection requires 1 mL of reconstituted solution, or 100 IU on a U-100 insulin syringe — which is a large volume for SC injection. Many researchers use 0.5 mL per injection (500 mcg) to reduce injection-volume discomfort. The peptide storage stability guide covers lyophilized vs reconstituted stability considerations in detail.
Safety profile: CJC-1295 specifics
The Teichman 2006 trial reported generally good tolerability. The GHRH-analog class does not have the cortisol and prolactin side-effect profile of non-selective GHRPs. Key safety considerations specific to CJC-1295 DAC:
- GH-driven insulin resistance. Sustained IGF-1 elevation from weekly CJC-1295 produces insulin-counter-regulatory effects, though less acutely than MK-677's 24-hour sustained profile. Relevant for individuals with any metabolic risk.
- Water retention. GH-driven sodium/water retention is a class effect; less severe than with pharmacological GH doses but present at extended use.
- Pituitary down-regulation (theoretical). Whether prolonged GHRH-R stimulation by a long-acting analog causes GHRH-R desensitization or somatotroph exhaustion is not adequately studied. The Ionescu 2006 paper's finding that pulsatile GH secretion persists is reassuring but not definitive for long-term use.
- Long-term safety in healthy adults. Not studied. The Teichman 2006 trial observed subjects for up to 28 days after injection; no multi-year safety data exists for CJC-1295 in healthy adults.