Research-use notice: This article summarizes published, patent, analytical, registry, and regulatory evidence. It is not medical advice, treatment guidance, or a recommendation for human use. First Due Biotech products are offered strictly for laboratory research use only and are not for human consumption.
Looking for the shorter version? Start with the CJC-1295 Without DAC Research Overview.
The short version
CJC-1295 without DAC is most defensibly defined as the amidated, four-substitution 29-mer [D-Ala²,Gln⁸,Ala¹⁵,Leu²⁷]-hGRF(1-29)-NH₂. Commercial sources commonly call the same intended sequence Modified GRF (1-29), but neither marketplace name reliably proves identity.
The original peer-reviewed ConjuChem program used CJC-1295 for a different molecule: the tetrasubstituted core plus a C-terminal maleimide-lysine Drug Affinity Complex that covalently binds albumin. The familiar human CJC-1295 studies evaluated that long-acting DAC molecule. P001, P013–P016
Direct evidence for the non-DAC core is sparse. It includes patent rat-pituitary and acute rat GH-release experiments, qualitative rat disposition/detection, and forensic identification of one seized preparation. No qualifying peer-reviewed human PK, PD, efficacy, or safety study of the exact non-DAC peptide was identified. P001–P004
What readers should remember
- The core sequence is reasonably defined, but its common names are historically and commercially ambiguous.
- Human DAC findings cannot be transferred to the non-DAC peptide.
- Direct biological-activity evidence is limited to patent and rat systems.
- The claimed 30-minute human half-life is unverified.
- Direct human benefits and adverse-event incidence are absent, not merely limited.
- Regulatory and product-quality concerns are more developed than the therapeutic evidence.
Evidence at a glance
| Research area | Current assessment | Central limitation |
|---|---|---|
| Intended molecular sequence | Moderate-to-high | Commercial identity remains inconsistent |
| Historical nomenclature | Low-to-moderate | “Without DAC” is a later retronym |
| Rat pituitary/GH activity | Low | Patent evidence with incomplete quantitative reporting |
| Rat disposition | Low | Conflicting assay detectability; no quantitative core PK |
| Human pharmacokinetics | Absent | DAC and partial-analogue data are non-transferable |
| Human GH/IGF-1 response | Absent | Published human CJC studies used DAC |
| Human outcomes | Absent | No direct body-composition, sleep, recovery, cognitive, or performance trials |
| Human safety profile | Absent | No adequate exact-molecule dataset |
| Chronic toxicology | Absent | No exact-molecule chronic program identified |
| Regulatory non-approval | High | Status should be periodically refreshed |
Identity, sequence, and nomenclature
For this review, CJC-1295 without DAC means:
Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH₂
Relative to human GRF/GHRH(1-29)-NH₂, the peptide substitutes D-Ala², Gln⁸, Ala¹⁵, and Leu²⁷. FDA reports formula C152H252N44O42, average molecular weight 3,367.95 g/mol, and CAS 446036-97-1 for the free base. Knoop and colleagues independently used the same positional identity and reported a compatible monoisotopic mass. P002, P004
Free base and acetate are separate bulk substances containing the same intended active peptide moiety. The DAC forms contain a different active moiety because they add the maleimide-bearing lysine extension. A product label alone cannot establish salt form, stereochemistry, impurity profile, aggregation state, or absence of the DAC extension. P004, P009
Modified GRF (1-29): qualified synonym
FDA documented commercial use of “CJC-1295 without DAC (mod-GRF 1-29),” supporting the conclusion that the terms often refer to the same intended sequence. No authoritative USAN or INN designation was located. “Modified GRF (1-29)” should therefore be treated as a descriptive name whose exact molecular meaning must be verified. P004
Why the original name points to DAC
ConjuChem’s patent calls the bare tetrasubstituted core Example 5. Example 6 appends Lys(MPA), whose maleimide group is designed to react with albumin Cys34. The 2005 development paper identifies this albumin-binding derivative as CJC-1295. P001, P013
“CJC-1295 without DAC” appears to be a later retronym for the precursor/core peptide marketed without the albumin-binding extension. FDA adopted the distinction for its 2024 regulatory evaluation while documenting ongoing naming confusion. P004
Development and structural rationale
Earlier GHRH analogue programs tested substitutions intended to reduce enzymatic cleavage, oxidation, or rapid clearance. In ten healthy men, D-Ala²-GHRH(1-29)-NH₂—a partial analogue lacking the other three substitutions—showed a longer disappearance half-time and lower metabolic clearance than native GHRH(1-29)-NH₂. This supports the D-Ala² design rationale, not the complete molecule’s human PK. P010
Other PEGylated and multi-substitution GHRH analogues predated ConjuChem, but their sequences and chemical modifications differ. They can inform development history and class mechanism, not effect estimates for the dossier compound. P011, P012
The defining structural distinction is the albumin-reactive extension. Without it, the peptide cannot form the intended covalent albumin adduct that produced the long exposure of original CJC-1295. P001, P013
Mechanism of action
The expected proximal mechanism is GHRH-receptor activation on pituitary somatotrophs, Gs/adenylyl-cyclase/cAMP signaling, and endogenous GH release, followed by hepatic and peripheral IGF-1 production.
For the exact non-DAC core, the patent reports GH release from cultured rat anterior-pituitary cells and an acute GH response in male rats. It does not provide a complete peer-reviewed receptor-binding constant, human receptor potency, signaling-bias profile, or human GH/IGF-1 dose-response. P001
Downstream claims involving body composition, sleep, healing, cognition, metabolism, or physical function require outcome-specific human research. Rat pituitary activity establishes only a proximal biological signal.
Pulsatility claim
The claim that non-DAC CJC-1295 “preserves natural GH pulses” is unsupported by a direct study. Ionescu and Frohman observed persistent pulsatility after the albumin-binding molecule, alongside markedly elevated trough GH and an approximately eight-day half-life. P015
That finding does not establish the shorter peptide’s pulse frequency, amplitude, troughs, timing, safety, or comparative physiology.
Pharmacokinetics and pharmacodynamics
Direct non-DAC evidence
The patent compared Example 5 with the albumin-reactive derivative in male rats. Example 5 was not detected after 60 minutes by the reported radioimmunoassay following intravenous or subcutaneous exposure. The DAC derivative remained detectable through 96 hours. No numerical half-life, clearance, bioavailability, or exposure estimate was reported for Example 5. P001
Knoop and colleagues later detected intact non-DAC peptide at two, four, and eight hours after intravenous exposure in a very small Wistar-rat experiment. The work was qualitative and analytical; it did not model PK or measure GH, IGF-1, safety, or efficacy. P002
Assay sensitivity, design, dose, matrix, or material differences may explain the detection-window conflict. It should not be converted into an eight-hour half-life or used to validate the frequently repeated 30-minute estimate.
Human unknowns
No qualifying direct study established human absorption, bioavailability, half-life, clearance, distribution, metabolism, excretion, dose proportionality, GH response, IGF-1 response, immunogenicity, or interaction effects.
The 5.4–9.2-day half-life, multi-day detectable concentrations, sustained GH, and prolonged IGF-1 elevation reported in human CJC-1295 literature belong to the DAC molecule. P014, P015
Human evidence
Exact non-DAC peptide
No peer-reviewed human interventional study of the verified four-substitution non-DAC peptide was identified. FDA’s 2024 review likewise found no human studies for free base or acetate, no clinical safety information, no studies establishing their pharmacologic activity, and no effectiveness data for the nominated growth-hormone-deficiency use. P004
There are therefore no direct human outcome data for body composition, metabolic markers, sleep, recovery, injury healing, cognition, physical performance, function, quality of life, or disease endpoints.
DAC human studies quarantined from attribution
Teichman and colleagues studied long-acting, albumin-binding CJC-1295 in 66 healthy adults across two phase I protocols. Multi-day PK and prolonged GH/IGF-1 changes cannot be transferred to the non-DAC core. P014
Ionescu and Frohman studied 12 healthy men one week after the long-acting molecule. Their pulse findings and IGF-1 response belong to DAC exposure. P015
Sackmann-Sala and colleagues analyzed serum proteins in 11 men from the same DAC cohort. It is a reused subset, not an independent trial. P016
NCT00267527 was a terminated long-acting/DAC phase II program in HIV-associated visceral obesity. Primary efficacy results were not published, and the trial does not supply non-DAC evidence. P004, P017
Preclinical, analytical, and forensic evidence
Patent cell and rat pharmacology
Example 5 stimulated GH release from cultured rat anterior-pituitary cells and produced an acute GH response in male rats. Eight rats per group were described for the acute comparison, but accessible patent reporting does not provide a clean quantitative potency estimate for the core. P001
Analytical rat study
Knoop and colleagues developed a mass-spectrometry method for GHRH analogues and reported intact non-DAC peptide through the last sampled time point at eight hours in a very small rat experiment. This establishes analytical detectability under that design, not therapeutic efficacy or safety. P002
Forensic identity
Henninge and colleagues identified a 29-amino-acid amidated peptide in a seized unknown preparation as consistent with a marketed CJC-1295 product. The finding documents illicit-market presence; it cannot establish consistency across products or any biological outcome. P003
Evidence explicitly excluded
Jetté’s albumin conjugation and prolonged rat exposure, DAC animal growth studies, and FDA-summarized long-acting toxicology concern DAC or incompletely specified long-acting material. They are relevant to identity history and transfer controls—not exact non-DAC efficacy or safety. P004, P013
Safety evidence and unresolved risks
No direct human safety dataset or exact-molecule chronic toxicology program was identified. Event rates cannot be assigned for headache, flushing, local reactions, edema, glucose changes, hypotension, tachycardia, or any other outcome. P004
FDA identified plausible GH/IGF-1-related hazards, including glucose intolerance, fluid retention, intracranial hypertension, neoplasm-related concerns, and endocrine interactions. These are mechanistic or class cautions, not observed non-DAC incidence estimates. P004
Product-quality hazards add a separate uncertainty. FDA reported incomplete characterization involving identity, impurities, aggregation, endotoxin or bioburden, and certificates of analysis. It also noted a theoretical cross-reactive-antibody concern without direct non-DAC immunogenicity data. P004
Adverse events from DAC trials must not be transferred. Conversely, absence of adverse-event reporting in brief rat or analytical work is not affirmative safety evidence.
Long-term malignancy, pituitary pathology, cardiovascular effects, glucose effects, fertility, pregnancy, development, pediatric and geriatric safety, renal or hepatic impairment, interactions, and overdose remain uncharacterized.
Regulatory and anti-doping history
No FDA-approved drug containing the exact non-DAC peptide was identified. FDA evaluated non-DAC free base, acetate, and three DAC-related forms for the Section 503A Bulks List in 2024. The agency cited identity inconsistency, inadequate characterization, absent exact-molecule safety and effectiveness evidence, plausible class risks, lack of pediatric data, and available approved alternatives for the nominated condition. P004
PCAC voted 0–13 against inclusion of free base and 1–12 against acetate. These are documented advisory outcomes, not drug-approval decisions or, by themselves, final rulemaking. P005, P006
WADA’s 2026 Prohibited List names CJC-1295 under growth hormone-releasing factors and prohibits the class at all times. The listing does not distinguish DAC from non-DAC forms. P007
Health Canada’s cited alert concerns unauthorized injectable peptide products generally and does not establish a compound-specific authorization or clinical effect. P008
How to interpret the evidence
Five controls are essential:
- Require exact molecular identity. “CJC-1295” alone is ambiguous.
- Quarantine DAC data. Albumin binding changes exposure enough to invalidate quantitative transfer.
- Separate plausible mechanism from human effect. Rat GH release does not prove body-composition or recovery outcomes.
- Treat negative searches carefully. No qualifying study identified does not prove that no unpublished experiment exists.
- Do not interpret missing safety data as safety. There is no adequate denominator.
Research gaps
- Verified human PK and bioavailability
- Direct human GH, IGF-1, glucose, and broader endocrine pharmacodynamics
- Human receptor potency, selectivity, and desensitization
- Quantitative preclinical PK resolving the patent/analytical detection conflict
- Defined free-base versus acetate characterization
- Controlled human outcome research
- Human adverse-event and immunogenicity data
- Chronic toxicology, carcinogenicity, reproductive, and developmental studies
- Independent product-identity and impurity characterization
- Final regulatory disposition following the PCAC recommendation
- Direct controlled evidence for any combination with ipamorelin
Conclusion
CJC-1295 without DAC is most defensibly defined as the tetrasubstituted, amidated 29-residue GHRH analogue that ConjuChem’s patent called Example 5. “Modified GRF (1-29)” commonly points to the same intended sequence, but it is not standardized enough to guarantee identity from a label.
Direct evidence supports limited rat-system GHRH-pathway activity and analytical detectability. It does not establish human PK, GH/IGF-1 response, efficacy, body composition, sleep, recovery, cognition, physical function, or safety.
The original CJC-1295 human literature belongs to the albumin-binding DAC molecule. Its multi-day exposure and endocrine findings cannot be repackaged as evidence for the non-DAC core.
The evidence-weighted conclusion is narrow: the peptide has a plausible and sparsely demonstrated proximal mechanism, while its human pharmacology, outcomes, and safety remain essentially uncharacterized.