Peptide Research Profile

CJC-1295

Modified GHRH(1-29) — Long-Acting Growth Hormone-Releasing Hormone Analog

Evidence Grade: Phase 1/2 Human Data · No FDA Approval

A synthetic analog of the first 29 amino acids of growth hormone-releasing hormone (GHRH), modified with four amino acid substitutions to resist DPP-4 cleavage. Two forms exist: CJC-1295 with DAC (Drug Affinity Complex — a maleimidopropionic acid linker enabling covalent albumin binding for ~8-day half-life) and CJC-1295 without DAC (also called Modified GRF 1-29 or Mod GRF, with a half-life of ~30 minutes). The DAC version has Phase 1/2 human data showing sustained GH and IGF-1 elevation. The no-DAC version is preferred in the community for pulsatile dosing.

Medical Disclaimer: This profile is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment recommendations. CJC-1295 is not FDA-approved. Two distinct forms (with and without DAC) exist with different pharmacokinetics. Always consult a qualified healthcare professional before using any peptide compound. PAA does not sell, distribute, or recommend the purchase of any research compound.

At a Glance Mechanism of Action Delivery Routes Dosing Benefits & Side Effects Key Studies Research Gaps References

Quick Reference

At a glance

Classification

GHRH Analog

Modified GHRH(1-29) with DPP-4-resistant amino acid substitutions

Key Forms

With DAC / No DAC

DAC version: ~8-day t½ (sustained) • No-DAC (Mod GRF): ~30 min t½ (pulsatile)

Evidence Level

Phase 1/2 Human

Teichman et al. (2006) • Single & multi-dose escalation • n=33 per study

Key Pathway

GHRH-R → Pituitary GH

Activates GHRH receptor on somatotrophs — Gαs/cAMP/PKA pathway

Pharmacology

Mechanism of action

CJC-1295 works through the same receptor and signaling pathway as endogenous GHRH and tesamorelin — it activates the GHRH receptor on pituitary somatotrophs to stimulate GH synthesis and secretion. The key innovation is pharmacokinetic: the DAC modification creates covalent albumin binding that extends the half-life from minutes to over a week, producing sustained (not pulsatile) GH elevation. This is both its advantage (convenient dosing) and its controversy (loss of physiologic pulsatility).

Subcutaneous Injection & Albumin Binding (DAC Version)

CJC-1295 with DAC uses a maleimidopropionic acid (MPA) linker that forms a covalent thioether bond with Cys34 on serum albumin within minutes of injection. This albumin conjugation protects the peptide from proteolysis and renal clearance, extending the effective half-life to approximately 8 days. A single subcutaneous injection maintains elevated GHRH receptor stimulation for over a week, producing sustained GH and IGF-1 elevation.

DAC chemistry: The Drug Affinity Complex is a reactive maleimide group attached via a lysine residue at the C-terminus of the modified GHRH(1-29) sequence. Maleimide reacts specifically with the free thiol of Cys34 on human serum albumin (the only unpaired cysteine in albumin’s 35 cysteine residues). The reaction is irreversible, creating a stable thioether bond. Once conjugated, the GHRH peptide circulates with the albumin carrier (half-life ~19 days). The effective drug half-life of ~8 days is shorter than albumin’s because the peptide moiety is eventually cleaved or inactivated while still attached. This bioconjugation approach is also used in insulin degludec and semaglutide (though those use non-covalent fatty acid/albumin binding).

CJC-1295 Without DAC (Mod GRF 1-29)

The no-DAC version (commonly called Modified GRF 1-29 or Mod GRF) retains the four amino acid substitutions for DPP-4 resistance but lacks the albumin-binding linker. Its half-life is approximately 30 minutes — dramatically shorter than the DAC version but 4x longer than native GHRH (~7 minutes). This shorter duration produces discrete GH pulses rather than sustained elevation, preserving the natural pulsatile pattern that many practitioners and community users prefer.

Amino acid modifications: The four substitutions that confer DPP-4 resistance are at positions 2 (D-Ala replaces Ala — prevents DPP-4 cleavage at the vulnerable N-terminal dipeptide), 8 (Gln replaces Asn — reduces asparagine deamidation), 15 (Ala replaces Gly — improves helical stability), and 27 (Leu replaces Met — prevents methionine oxidation). These substitutions collectively increase bioavailability and resistance to enzymatic degradation without altering GHRH receptor binding affinity. The resulting peptide (Mod GRF 1-29) is effectively “sermorelin 2.0” — sermorelin is unmodified GHRH(1-29) with the original ~7-minute half-life.

GHRH Receptor Activation & GH Release

Both forms activate the GHRH receptor (GHRHR) identically: Gαs → adenylyl cyclase → cAMP → PKA → CREB phosphorylation → GH gene transcription + granule exocytosis. The difference is temporal: the DAC version provides continuous receptor occupancy (like a GH-releasing infusion), while the no-DAC version provides a brief pulse of receptor stimulation followed by clearance and receptor recovery.

Pulsatile vs. sustained — the GH debate: Endogenous GH secretion is highly pulsatile, with major bursts during sleep and minor pulses throughout the day. Somatostatin from the hypothalamus creates the off periods between pulses. This pulsatility is not aesthetic — it is functionally important. Pulsatile GH drives STAT5b-mediated gene expression differently from continuous GH, which preferentially activates STAT5a/STAT3. In rodents, disrupting pulsatility (e.g., continuous GH infusion) changes liver gene expression, body composition patterns, and even sexual dimorphism of GH-responsive genes. The concern with CJC-1295 + DAC is that sustained GHRH stimulation may override somatostatin-mediated pulsatility, producing a more continuous GH profile. Whether this matters clinically in adults using it for body composition is debated but unstudied.

Sustained IGF-1 Elevation (DAC Version)

In Phase 1 studies, a single 60 mcg/kg dose of CJC-1295 with DAC elevated mean IGF-1 levels by 1.5–3x baseline for 6–14 days. With weekly dosing, IGF-1 remained persistently elevated. This sustained IGF-1 elevation is the mechanism for claimed anabolic and body composition benefits, but also raises the theoretical long-term safety question of chronic supraphysiologic IGF-1 exposure.

IGF-1 kinetics: After a single dose, GH levels rise within 2 hours and remain elevated for 6+ days. IGF-1 (produced hepatically in response to GH) rises more slowly, peaking at ~day 3–5 and remaining elevated for ~14 days. With repeated weekly dosing, both GH and IGF-1 reach a new steady state above baseline. The Phase 1 data showed IGF-1 levels 200–300% above baseline at steady state — this is above the physiologic range and enters the territory associated with acromegalic features if maintained chronically. The clinical significance of this level of IGF-1 elevation depends on duration of exposure and individual variability.

Synergy with GH Secretagogues (Community Protocol)

The no-DAC version (Mod GRF 1-29) is commonly combined with ipamorelin or other GHS peptides to exploit GHRH/GHS synergy. GHRH activates the cAMP pathway, while GHS activates the calcium/PKC pathway — co-stimulation produces 2–3x the GH response of either alone. This combination attempts to maximize the GH pulse amplitude while preserving pulsatility through the short half-life of both components.

Protocol rationale: The typical community “GH stack” of Mod GRF (100 mcg) + ipamorelin (200 mcg) dosed 1–3x daily attempts to replicate the physiology of a young person’s GH secretion pattern: discrete pulses of high-amplitude GH separated by periods of low/undetectable GH. The short half-lives (30 minutes and 2 hours respectively) allow full clearance between doses, preserving somatostatin-mediated interpulse troughs. The DAC version, by contrast, provides no interpulse troughs and is therefore less often combined with GHS peptides — the sustained GHRH stimulation would override the pulsatile benefit.

Administration

Delivery routes

Subcutaneous Injection

Primary — Both Forms

The standard route for both DAC and no-DAC versions. CJC-1295 with DAC is typically dosed once or twice weekly (exploiting the long half-life). CJC-1295 without DAC (Mod GRF) is dosed 1–3 times daily, often before bed or before meals, similar to ipamorelin. Both are reconstituted from lyophilized powder with bacteriostatic water.

Intravenous

Clinical Research Only

IV administration was used in the Phase 1 studies to establish PK/PD parameters. Produces rapid GHRH receptor activation. Not practical for repeated self-administration and offers no advantage over SC for the DAC version (which achieves sustained levels regardless of route).

Oral

Not Viable

A 29-amino-acid peptide is completely degraded by gastrointestinal proteases regardless of the amino acid modifications. No oral formulation exists or is feasible.

Intranasal

Not Developed

The ~3.4 kDa molecular weight (without DAC) is borderline for nasal absorption. No studies have tested intranasal delivery of either CJC-1295 form. Nasal bioavailability is expected to be low and unreliable compared to subcutaneous injection.

Protocols

Dosing reference

Phase 1 data exists for CJC-1295 with DAC. The no-DAC version (Mod GRF 1-29) dosing is extrapolated from community experience and GHRH pharmacology. The two forms require fundamentally different dosing schedules.

Context	Dose	Frequency	Source
CJC-1295 + DAC (Phase 1)	30–60 mcg/kg SC Single doses in dose-escalation study	Once weekly (sustained levels)	Teichman et al., 2006
CJC-1295 + DAC (community)	1–2 mg SC Reconstituted from lyophilized powder	1–2x per week	Community protocols / practitioner use
Mod GRF 1-29 / No DAC (community)	100 mcg SC Per injection, often combined with GHS	1–3x daily, pre-bed or pre-meal	Community protocols
Mod GRF + Ipamorelin combo	100 mcg Mod GRF + 200 mcg Ipamorelin Simultaneous SC injection	1–2x daily for 8–12 weeks	Community protocols / practitioner use

Important: CJC-1295 is not FDA-approved for any indication. The DAC and no-DAC versions are not interchangeable — their pharmacokinetics differ by a factor of ~400x in half-life. Mixing up the two forms could result in either underdosing or dangerously prolonged GH elevation. The no-DAC version is pharmacologically similar to tesamorelin and sermorelin but lacks their regulatory pedigree and quality assurance.

Outcomes

Benefits & side effects

Reported Benefits

Sustained GH & IGF-1 Elevation (DAC)

A single injection elevates GH and IGF-1 for 6–14 days. Weekly dosing maintains steady-state IGF-1 at 1.5–3x baseline. This convenience factor (once-weekly dosing) is the primary practical advantage over daily GHRH analogs or multiple-daily GHS injections.

Phase 1 human PK/PD • Teichman et al., 2006 • n=33

Pulsatile GH Stimulation (No DAC)

The no-DAC version preserves natural GH pulsatility while amplifying pulse amplitude. When combined with a GHS (ipamorelin), it exploits GHRH/GHS synergy for maximal pulse amplitude with full interpulse recovery. This is considered the more physiologic approach to GH optimization.

GHRH/GHS synergy literature • Community experience • No direct RCT

Improved Body Composition

Users report reductions in body fat and improvements in lean tissue, consistent with the known effects of GH/IGF-1 on lipolysis and protein synthesis. The Phase 1 studies did not include body composition endpoints, so this benefit relies on mechanistic extrapolation and uncontrolled reports.

Mechanistic plausibility • Community reports • No body composition RCT

Theoretical Tissue Repair

GH/IGF-1 axis stimulation promotes collagen synthesis, chondrocyte proliferation, and tissue remodeling. Some practitioners prescribe CJC-1295 +/- ipamorelin for injury recovery, tendon healing, or post-surgical recovery. These applications have no direct clinical evidence for CJC-1295 specifically, though GH’s role in tissue repair is well-established.

GH biology • No CJC-1295-specific tissue repair data

Adverse Effects & Risks

Injection Site Reactions

The DAC version, in particular, can cause local induration and erythema at the injection site due to the bioconjugation chemistry. The maleimide-albumin reaction occurs locally before systemic distribution. Rotating injection sites is recommended.

Phase 1 AE data • Mild

Water Retention & Flushing

Similar to other GH-axis stimulants: transient facial flushing, mild peripheral edema, and sensation of warmth post-injection. More pronounced with the DAC version due to sustained GH elevation. Generally self-limiting within the first 1–2 weeks.

Phase 1 data + community reports

Non-Pulsatile GH Concerns (DAC Version)

The sustained GH elevation from the DAC version may override somatostatin-mediated pulsatility, producing a GH profile more similar to continuous GH infusion than natural secretion. This could theoretically alter GH-responsive gene expression patterns, change body composition outcomes, and potentially increase insulin resistance compared to pulsatile approaches. This concern is theoretical but pharmacologically grounded.

Theoretical — based on GH pulsatility literature

Hypoglycemia Risk (With GHS Combo)

When combined with GHS peptides (ipamorelin, GHRP-2) and administered in the fasted state, some users report symptoms suggestive of transient hypoglycemia (lightheadedness, sweating). GH itself is counter-regulatory, but the acute insulin-sensitizing phase of early GH elevation can transiently lower glucose before the counter-regulatory effect dominates.

Community reports • Occasional • Self-limiting

Unknown Long-Term Safety

Maximum human exposure in published studies was 4 weekly doses. No data exists for the community-standard 8–12-week cycles or longer. Chronic supraphysiologic IGF-1 elevation (especially with the DAC version) has theoretical oncologic and metabolic risks.

Complete absence of long-term data

Evidence Base

Key studies

Phase 1 — Single Ascending Dose

Prolonged Stimulation of GH and IGF-1 by CJC-1295 with DAC

Teichman et al. • J Clin Endocrinol Metab • 2006 • n=33

Design & Findings

Single SC doses of CJC-1295 + DAC (30, 60, 90 mcg/kg) in healthy adults. GH levels increased 2–10-fold for up to 6 days. IGF-1 increased 1.5–3-fold for 8–14 days. Dose-response was linear. No serious adverse events. ACTH and cortisol were unaffected.

Significance

Proof-of-concept for the DAC bioconjugation technology. Demonstrated that covalent albumin binding can produce week-long GHRH-like activity from a single injection. This PK profile is unique among peptide GHRH agonists.

Limitations

Phase 1 — small sample (n=33 across dose groups). Single-dose study. No body composition or clinical outcome endpoints. No comparison to daily GHRH analogs. Healthy young adults only. Industry-funded (ConjuChem).

View on PubMed

Phase 1 — Multiple Ascending Dose

Multiple-Dose Pharmacokinetics of CJC-1295 with DAC

Teichman et al. • J Clin Endocrinol Metab • 2006 • n=33 (separate cohort)

Design & Findings

Weekly SC dosing (30–90 mcg/kg) for 4 weeks. Steady-state IGF-1 elevation of 1.5–3x baseline was maintained throughout the dosing period. GH elevation was sustained between doses. No tachyphylaxis over 4 weeks. Mild injection site reactions and facial flushing were the most common AEs.

Significance

Confirms sustained efficacy with repeated weekly dosing and absence of acute tachyphylaxis. The steady-state IGF-1 data provides the basis for community dosing protocols.

Limitations

Only 4 weeks of dosing. Small sample. No efficacy endpoints measured. 4 weeks is insufficient to assess tachyphylaxis (GHS-R desensitization studies suggest this may emerge at 6–8 weeks). No comparison to other GHRH analogs.

View on PubMed

Preclinical — GH Pulsatility Comparison

Continuous vs. Pulsatile GHRH: Effects on GH Secretory Pattern

Various authors • Endocrine Reviews • Synthesis of multiple studies

Design & Findings

Rodent and human studies consistently show that pulsatile GHRH administration produces larger GH pulses than continuous infusion (due to somatotroph recovery between pulses). Continuous GHRH can desensitize somatotrophs and reduce pulse amplitude over days. These findings inform the preference for no-DAC (pulsatile) over DAC (sustained) versions in some clinical philosophies.

Significance

Provides the scientific basis for community and practitioner preference for Mod GRF (no-DAC) over DAC CJC-1295. The pulsatility data is robust and comes from multiple independent research groups over decades.

Limitations

Synthesis of studies, not a single definitive trial. Most pulsatility research used native GHRH or sermorelin, not CJC-1295 specifically. The clinical relevance of pulsatility differences for adult body composition goals (vs. growth in children) is debated.

View on PubMed

Open Questions

Research gaps

No Approved Indication

ConjuChem Biotechnologies developed CJC-1295 + DAC through Phase 1/2 but did not progress to Phase 3 before the company’s restructuring. Clinical development is effectively abandoned. No regulatory body has evaluated CJC-1295 for safety or efficacy approval.

No Body Composition or Clinical Outcome Data

The Phase 1 studies measured only PK/PD (GH/IGF-1 levels). No trial has evaluated CJC-1295’s effects on body fat, lean mass, sleep quality, recovery, or any clinical outcome in controlled conditions.

DAC vs. No-DAC Never Compared in Humans

The community strongly debates DAC vs. no-DAC versions, but no clinical study has directly compared them for any outcome. The theoretical advantages of pulsatile (no-DAC) over sustained (DAC) GH stimulation have not been tested in a head-to-head trial.

Long-Term Safety Unknown

Maximum published human exposure is 4 weeks. Community use extends to months or years. Chronic effects of sustained supraphysiologic IGF-1 (DAC version) or repeated GH pulsing (no-DAC version) on cancer risk, insulin resistance, pituitary function, and cardiovascular health are completely unstudied.

Quality Control Concerns

CJC-1295 is available only from compounding pharmacies and research chemical suppliers. The DAC bioconjugation is a sophisticated chemical reaction — quality assurance for the maleimide linker’s integrity, albumin-binding efficiency, and peptide purity varies wildly between suppliers. Mislabeling (DAC vs. no-DAC) is a known issue in the gray market.

Combination Protocols Untested

The Mod GRF + ipamorelin combination, despite being the most common community GH protocol, has zero human clinical trial data. Dose ratios, timing, safety, and actual synergistic GH response in vivo have never been formally characterized.

Citations

References & further reading

1. Teichman SL, Neale A, Lawrence B, et al. 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. PubMed

2. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295. J Clin Endocrinol Metab. 2006;91(12):4792-4797. PubMed

3. Alba M, Fintini D, Sagazio A, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone analog, normalizes growth in the IGHD rat. J Endocrinol. 2006;190(1):159-167. PubMed

4. Thorner MO. The discovery of growth hormone-releasing hormone. J Clin Endocrinol Metab. 1999;84(12):4671-4676. PubMed

5. Veldhuis JD, Iranmanesh A, Bowers CY. Joint mechanisms of impaired growth-hormone pulse renewal in aging men. J Clin Endocrinol Metab. 2005;90(7):4177-4183. PubMed

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