CJC-1295 (no-DAC)

Endogenous GHRH (growth hormone-releasing hormone) is a 44-amino acid peptide produced by hypothalamic neurons and transported via the portal blood to the anterior pituitary. The first 29 amino acids (GHRH 1-29) contain the full receptor-binding and activation domain; amino acids 30-44 contribute to plasma stability and half-life extension but not receptor activation. GHRH itself has a plasma half-life of only 4-7 minutes, primarily because dipeptidyl peptidase IV (DPP-IV) cleaves the Ala-Asp bond between positions 2 and 3, rapidly inactivating the peptide. This is why native GHRH is not useful as a therapeutic agent — it would need continuous infusion to maintain meaningful receptor activation.

Modified GRF 1-29 (CJC-1295 no-DAC) makes four substitutions in the GHRH(1-29) sequence: (1) Ala⁸→Gln: the primary DPP-IV resistance modification; DPP-IV cannot cleave the modified bond; (2) Gly¹⁵→Ala: reduces endopeptidase cleavage at position 15; (3) Arg¹⁸→Ala: improves chemical stability; (4) Gln²⁶→Ala: reduces asparagine deamidation at position 25 (a common degradation pathway for Gln-containing peptides). These four changes extend the plasma half-life from 4-7 minutes to approximately 30 minutes without meaningfully changing GHRH receptor binding affinity. The result: a GHRH analog that survives long enough after subcutaneous injection to reach the pituitary and drive a discrete GH pulse before clearing.

CJC-1295 WITH DAC adds a maleimidoproprionic acid (MPA)-drug affinity complex on a Lys residue at the C-terminus. This complex forms a stable covalent bond with Cys-34 of serum albumin in blood. Since albumin has a ~21-day half-life and the CJC-DAC bond is stable, this effectively extends the peptide's circulating half-life to approximately 8 days. The structural difference is a Lys-MPA addition at the C-terminus. The functional difference is 30-minute pulsatile vs 8-day continuous. No other aspect of the GHRH receptor binding mechanism changes between the two forms.

Feature

CJC-1295 NO-DAC (Mod GRF 1-29)

CJC-1295 WITH DAC

Native GHRH(1-29) [Sermorelin]

Structure

GHRH(1-29) + 4 protease-resistance substitutions

Same + Lys-MPA-albumin binding complex

Unmodified GHRH(1-29) [Sermorelin = native GHRH(1-29)]

Plasma half-life

~30 min

~8 days

~4-7 min (Sermorelin ~10-12 min in some reports)

GH stimulation pattern

Pulsatile (one discrete GH pulse per injection)

Sustained continuous (non-pulsatile; blunts natural GH pulsatility)

Pulsatile (very short; near-continuous dosing needed at high frequency)

Protocol compatibility

Pulsatile (1-3x daily injection; synergistic with GHRP)

Continuous (weekly or biweekly injection; not for pulsatile protocols)

Pulsatile (daily injection; FDA-approved; less DPP-IV resistance than Mod GRF)

Synergy with GHRP

Yes — core principle of GH Stack

Theoretically yes but pulsatile protocol not applicable with 8-day t½

Yes — same as no-DAC

WADA

S2 — banned

S2 — banned

S2 — banned

Community use

Standard GH Stack component; 100-200 mcg/day

Less used in community; chronic GH elevation protocols

Less common than Mod GRF; FDA-approved for GH deficiency (withdrawn 2008 for economic reasons)

CJC-1295 (no-DAC) binds the GHRH receptor (GHRHR), a Class B GPCR on pituitary somatotrophs. Binding activates Gs protein → adenylyl cyclase → cAMP accumulation → PKA activation → multiple downstream effects: voltage-gated Ca²⁺ channel activation (triggers GH granule exocytosis); upregulation of Pit-1 transcription factor (GH gene expression); GH synthesis and secretion. A single injection of CJC-1295 (no-DAC) at community doses produces a GH pulse within 15-30 minutes that peaks at 30-60 minutes and returns to baseline within 2-3 hours. This mimics the normal nocturnal GH pulse pattern that naturally peaks during deep slow-wave sleep.

When CJC-1295 (no-DAC) is injected simultaneously with a GHRP (Ipamorelin, GHRP-6, or GHRP-2), the two compounds activate separate receptor systems on the same pituitary somatotroph: GHRHR (via CJC-1295) + GHS-R1a (via GHRP). The synergy is not simply additive; it is supraadditive (3-5x the GH pulse vs either alone). The mechanism: GHRH receptor activation increases intracellular cAMP and primes the somatotroph for GH release; GHS-R1a activation simultaneously releases somatostatin's inhibitory brake (by suppressing hypothalamic somatostatin tone via GHS-R1a on somatostatin neurons) and triggers GH exocytosis via Gq-Ca²⁺ pathway. The two mechanisms are not only non-overlapping but actively cooperative: GHRHR primes, GHS-R1a triggers, and the combined pulse is larger than the sum of parts. Bowers et al. (1991, Endocrinology) established this synergy with GHRH+GHRP-6; the principle applies to all GHRH+GHRP combinations.

Teichman SL, Neale A, Lawrence B, et al. (2006). 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. 91(3):799-805. This is the most-cited CJC-1295 paper in community discussions. What it actually studied: CJC-1295 WITH DAC — the albumin-binding version, not CJC-1295 no-DAC. Design: healthy adults; single SC injection of CJC-1295 WITH DAC at 30, 60, 90, or 120 mcg/kg; GH and IGF-1 measured for weeks. Results: IGF-1 elevated +35-89% (dose-dependent); peak GH response within 1-2 hours of injection; sustained GH elevation for 5-8 days (consistent with the albumin-bound half-life). This evidence is for the WITH DAC compound. It establishes that the GHRH analog mechanism works in humans and that the GHRH receptor can be effectively activated by synthetic analogs; the specific IGF-1 and GH data is for the 8-day half-life compound, not the pulsatile no-DAC form.

The GHRH+GHRP synergy that underlies all GH Stack use — including the CJC-1295 no-DAC + Ipamorelin combination — is established across multiple human studies. Bowers CY et al. (1991, Endocrinology 128:2027-35): GHRH + GHRP-6 produces 2-3x larger GH pulse than either alone in humans; the foundational synergy paper. Subsequent studies with GHRH + various GHRPs have consistently replicated the supraadditive GH pulse. The specific pulsatile CJC-1295 no-DAC + Ipamorelin combination in community doses has not been studied in a published Phase 2 RCT; the evidence is the class-level GHRH+GHRP synergy principle applied to these two specific peptides.

Sermorelin is native GHRH(1-29) without the four protease-resistance substitutions. It was FDA-approved for GH deficiency treatment in children and adults (Geref injectable; withdrawn 2008 for economic reasons, not safety). Sermorelin's human clinical evidence base is extensive: multiple Phase 2/3 trials in GH-deficient adults and children; GH and IGF-1 elevation confirmed; safe and effective for the approved indication. CJC-1295 no-DAC and Sermorelin have the same receptor mechanism (GHRH receptor) and differ primarily in plasma stability: ~30 min for Mod GRF vs ~10-12 min for Sermorelin. The Sermorelin evidence base informs the class mechanism that CJC-1295 no-DAC operates within.

Evidence

Grade

Finding

Limitation

Teichman 2006 (JCEM; Phase 2; CJC-1295 WITH DAC; n=64 adults; single SC injection)

B (human; WITH DAC)

IGF-1 +35-89% dose-dependent; GH elevated; 5-8 day sustained elevation consistent with albumin half-life; safe and well-tolerated

This is the WITH DAC compound, not CJC-1295 no-DAC; sustained GH, not pulsatile; not directly applicable to no-DAC protocol evidence

Bowers 1991 (Endocrinology; GHRH+GHRP synergy; humans)

B

GHRH+GHRP-6 produces 2-3x larger GH pulse than either alone; supraadditive synergy confirmed in humans; mechanism applies to all GHRH+GHRP combinations

Not CJC-1295 specifically; different GHRH used; class-level synergy principle

Sermorelin Phase 2/3 (GHRH(1-29); GH deficiency; FDA-approved)

A-B

GHRH receptor activation: GH and IGF-1 elevation confirmed; safe in adults and children; mechanism directly applies to CJC-1295 no-DAC (same receptor, very similar peptide)

Different peptide (no DPP-IV substitutions); slightly different PK; FDA approval was for GH deficiency, not general GH optimization

Community use of CJC-1295 no-DAC + Ipamorelin (GH Stack)

E

Widespread community consensus on GH pulse, IGF-1 elevation, sleep quality improvement, body composition; consistent independent reports

No controlled trial for this specific combination at community doses; Grade E evidence

CJC-1295 (no-DAC) alone (without a GHRP) produces a GHRH receptor-mediated GH pulse but without the GHS-R1a somatostatin suppression that ipamorelin provides. The GH pulse is real but smaller than with a GHRP co-injection. Some users run CJC-1295 no-DAC alone during rest periods from GHRP or for general GH axis support without the appetite stimulation of GHRP-6. The standalone protocol is less common because the GHRH+GHRP synergy makes the combination substantially more effective per injection.

Protocol Parameter

Recommendation

Notes

Dose

100-200 mcg per injection

Standard community range; 100 mcg adequate for synergistic GH Stack protocols; 200 mcg for higher GH pulse amplitude

Frequency

Daily (1x/day most common); some use 2x daily

GH Stack protocol: 1x before bed; advanced: AM fasted + PM bedtime for two daily pulses

Timing

Before bed (primary); AM fasted (secondary)

Bedtime amplifies natural sleep-phase GH pulse; AM fasted aligns with morning cortisol timing

Empty stomach

Mandatory: 2+ hours post-meal; 20-30 min before eating after injection

Insulin blunts GH release; this rule cannot be waived

Reconstitution

5 mg vial + 2 mL BAC water = 2.5 mg/mL

100 mcg = 4 units on U-100 syringe; 200 mcg = 8 units

Route

SubQ (abdomen, thigh, upper arm)

Rotate injection sites

Cycle length

8-12 weeks on; 4-8 weeks off

Same as GH Stack; allows GHRH receptor recovery

Stacking

Always with a GHRP (Ipamorelin preferred) for synergistic GH pulse

Same syringe administration acceptable; same timing

IGF-1 monitoring

Baseline + 6-8 weeks into cycle

Target upper half of age-appropriate reference range; do not exceed upper limit

Water retention: most common early adverse effect; GH-mediated sodium/water retention; peripheral edema in hands and feet; resolves within 2-4 weeks of stable dosing or on cycle end. Transient insulin resistance: GH antagonizes insulin signaling; fasting glucose may rise on extended cycles; monitor HbA1c in pre-diabetic individuals. Headache: occasional; resolves with dose reduction. Mild tingling or numbness in extremities: water retention and IGF-1 effects on soft tissues around nerves (mild carpal tunnel effect). These are class-level GH axis adverse effects, not CJC-1295-specific.

Unlike GHRP-6 and GHRP-2, CJC-1295 (no-DAC) does not directly stimulate cortisol or prolactin. GHRH receptor activation is specific to pituitary somatotrophs; there is no GHRH receptor-mediated adrenal axis or lactotroph activation. The cortisol and prolactin profile is clean. When stacked with Ipamorelin (which also has minimal cortisol/ACTH effect), the GH Stack produces essentially pure GH elevation without the HPA axis activation seen with less selective GHRPs like GHRP-6.

They share a base peptide sequence with 4 substitutions. CJC-1295 WITH DAC has an additional albumin-binding complex that changes the half-life from ~30 minutes to ~8 days. This is not a minor pharmacological difference — it changes the compound from a pulsatile secretagogue to a continuous GH elevator and makes it pharmacologically incompatible with the community pulsatile protocol. Always specify no-DAC and verify with the vendor.

Teichman 2006 studied CJC-1295 WITH DAC. The sustained IGF-1 elevation they measured reflects the 8-day half-life of the albumin-bound compound. CJC-1295 no-DAC at community doses (100-200 mcg/day) produces meaningful IGF-1 elevation, but the Teichman study numbers do not directly apply to the pulsatile no-DAC protocol. Community IGF-1 data for CJC-1295 no-DAC is Grade E (community consensus; consistent with class mechanism expectations).

Up to 2x daily may provide dual GH pulses (AM and PM). Beyond 2x daily, the GHRH receptor may partially desensitize between injections, reducing the incremental benefit of additional doses. Most users achieve their goals with 1x daily before bed. The 2x daily protocol is used by experienced users seeking dual GH pulses for more sustained IGF-1 elevation through the day.

No. The empty stomach rule is pharmacological: insulin suppresses GH release from the pituitary. Injecting CJC-1295 (no-DAC) within 2 hours of a meal means insulin is circulating and will blunt or abolish the GH pulse. The empty stomach requirement is not optional.

• Always confirm no-DAC: verify with vendor before purchasing that the product is CJC-1295 no-DAC / Mod GRF 1-29, not CJC-1295 WITH DAC.
• Always pair with a GHRP: CJC-1295 no-DAC produces a GH pulse alone but the supraadditive 3-5x synergy only occurs with simultaneous GHRP co-injection; Ipamorelin is the standard pairing (clean; no cortisol/prolactin).
• Empty stomach mandatory: 2+ hours post-meal; 20-30 min before eating after injection; bedtime is the natural timing solution.
• Dose: 100-200 mcg per injection; 100 mcg is adequate for synergistic GH Stack; 200 mcg for higher amplitude.
• IGF-1 monitoring: baseline and week 6-8; target upper half of age-appropriate reference range.
• WADA S2: banned in competition and out-of-competition; career-ending for any athlete under testing.
• See also: pbghstackv4 (GH Stack: CJC-1295 no-DAC + Ipamorelin protocol); pbcit_v4 (CIT Blend: CJC+Ipa+Tesamorelin).

— End of CJC-1295 (no-DAC) —

THE PEPTIDE BIBLE | CJC-1295 (no-DAC) / Modified GRF 1-29 | For Research & Educational Purposes Only