CJC-1295 (with and without DAC)

Two molecules under one name

CJC-1295 is not one compound. In its November 2024 evaluation for the section 503A bulk drug substances list, FDA separated the name into five distinct bulk drug substances resting on two distinct active moieties. The first is a 29-residue analogue of human growth hormone-releasing hormone, formula C152H252N44O42, molecular weight 3367.95 g/mol, CAS 446036-97-1. The second adds a thirtieth residue, a lysine bearing a 3-maleimidopropionamide group, giving C165H269N47O46 at 3647.95 g/mol, CAS 446262-90-4, UNII 62RC32V9N7. That maleimide is the drug affinity complex, and it is the whole point of the second molecule: it reacts with the free thiol of cysteine 34 on circulating albumin.

Registries do not hold the two apart. PubChem CID 91971820 is titled CJC-1295 and carries the maleimide, so the name resolves to the modified molecule. CID 56841945 is the plain 29-mer, and its synonym list contains “CJC 1295 with DAC” and “CJC-1295-no DAC acetate” simultaneously, plus a linear name string that describes the 30-residue conjugate. FDA recorded the same defect in its own database, noting that the Global Substance Registration System record named for the unmodified compound displays the structure of the modified one. The agency treated inconsistent naming as a safety risk in its own right.

Four substitutions distinguish the peptide backbone from native GHRH(1-29): D-alanine at position 2, glutamine at 8, alanine at 15 and leucine at 27. Jetté and colleagues, who built the molecule at ConjuChem, described these as intended to resist dipeptidyl peptidase-IV cleavage, asparagine rearrangement and methionine oxidation. The marketplace term “CJC-1295 without DAC” describes that backbone alone. It is also sold as modified GRF (1-29). The two labels point at the same 29 residues, and neither points at the molecule that the human trials used.

What was measured in healthy adults

Two randomised, placebo-controlled ascending-dose trials, running 28 and 49 days, make up the published human record. Teichman and colleagues reported both in 2006. In the first, 42 healthy adults aged 21 to 61 received a single subcutaneous dose, 35 on drug and seven on placebo. Mean plasma growth hormone rose 2- to 10-fold for six days or more, mean plasma IGF-I rose 1.5- to 3-fold for nine to eleven days, and the estimated half-life was 5.8 to 8.1 days. IGF-I exceeded age- and sex-adjusted normal ranges only in the group given 250 mcg/kg.

In the second trial, 24 subjects were split into four groups of six, one of whom received placebo in each. Maximum plasma concentrations after the day-14 injection ran 29 to 70 percent above those on day 0 across all four groups, and mean IGF-I stayed above baseline through day 28. The estimated half-life in that trial ranged from 5.4 to 9.2 days. Individual variability in maximum concentration was described as high and as increasing with successive doses, without a dose relationship.

Ionescu and Frohman sampled blood every 20 minutes across a 12-hour overnight period in 12 healthy men, before and one week after a single injection. Pulse frequency and pulse magnitude were unaltered. Trough growth hormone rose 7.5-fold, mean growth hormone rose 46 percent, and IGF-I rose 45 percent. IGF-I did not exceed the upper limit of normal in any subject, and the IGF-I increases correlated with no measured parameter of growth hormone secretion. Eleven of those twelve men supplied the serum for a 2009 proteomics analysis by Sackmann-Sala and colleagues, which identified candidate protein markers rather than any clinical outcome.

Adverse events were recorded in 33 of 35 subjects on drug in the first Teichman trial, against two of seven on placebo. Injection-site reactions occurred in roughly 70 percent, transient urticarial rashes at the injection site in almost 30 percent, headache in 63 percent against 14 percent on placebo, diarrhoea in 43 percent, and systemic vasodilatory reactions in 30 percent. In the second trial every subject on drug had an injection-site reaction, and flushing was dose-related, reaching 100 percent after high-dose injections. Both trials reported no consistent change in blood or urine laboratory values, including glucose.

The trial that was stopped

One trial of CJC-1295 in a patient population is registered. NCT00267527 was a multicentre, randomised, double-blind, placebo-controlled phase 2 study of 12 weeks of treatment in people with HIV-associated visceral obesity, sponsored by ConjuChem, started December 2005. The registry lists enrolment at 120, status terminated, completion September 2006, and no posted results. The record carries no reason for termination and was last updated in October 2006. Nothing from it has been published in the peer-reviewed literature in the twenty years since.

What happened is documented only in contemporaneous news reporting, which FDA characterised in 2024 as anecdotal. Those reports describe 192 subjects enrolled and randomised to escalating low-dose or high-dose weekly injections or placebo. Two hours after an eleventh weekly dose, one subject reported chest discomfort; an electrocardiogram confirmed an acute myocardial infarction and the subject died approximately one hour later. The attending physician's stated explanation was asymptomatic coronary artery disease with plaque rupture and occlusion. No independent adjudication of that attribution has been published, and no information about adverse events in the other subjects has ever appeared.

The registered enrolment figure and the reported one disagree by 72 people, and neither can be checked against a results table. This is the central hole in the CJC-1295 record. Every published human observation comes from healthy volunteers, most of whom received a single injection; the one study that ran for twelve weeks in people with a condition produced a fatality report in the trade press and nothing else.

Animal and cell findings

Jetté and colleagues characterised the molecule in male Sprague-Dawley rats in 2005. A single subcutaneous injection produced a 4-fold increase in growth hormone area under the curve over two hours compared with hGRF(1-29). Plasma concentrations peaked around 30 minutes and remained detectable beyond 72 hours, against one hour for hGRF(1-29) under similar conditions. Western blotting detected immunoreactive material on the albumin band from 15 minutes onward. Growth hormone returned to baseline by two hours while the peptide was still circulating, which the authors could not explain and offered three hypotheses for. Group sizes were not stated in the retrieved report.

Alba and colleagues treated GHRH knockout mice from one week of age for five weeks, at intervals of 24, 48 or 72 hours. Animals dosed every 24 hours reached body weight and length comparable to heterozygous controls; those dosed every 48 or 72 hours grew larger than placebo-treated knockouts without full normalisation. Total pituitary RNA and growth hormone mRNA increased, and immunohistochemistry was read as showing somatotroph proliferation. The retrieved report does not state group sizes. The model has no endogenous GHRH at all, which is the reason the result cannot be carried across to animals with an intact axis.

Ben-Shlomo and colleagues used the compound as a tool in a 2020 study of pituitary adenoma biology, and that work produced the only genotoxicity signal in the file. Four-month-old male C57BL/6 mice received 10 mcg/kg subcutaneously three times weekly for eight weeks: 16 on drug, 15 on phosphate-buffered saline. Pituitary glands from treated mice weighed 47 percent more. Comet assay and γH2AX phosphorylation both indicated DNA damage in the pituitary. In primary mouse pituitary culture, 10 ng/mL over 16 hours raised growth hormone and produced the same two DNA damage readouts, at six replicates per group.

Everything else in the toxicology file exists only as conference abstracts, and is known through FDA's summary of them rather than through retrievable papers. Those abstracts describe single-dose work in rats and beagle dogs, 14-day repeat-dose work in both species, a developmental study in pregnant rats, and a six-month immunogenicity study in cynomolgus monkeys. FDA reported injection-site haemorrhage, inflammation and necrosis in rats and dogs at all tested doses, and read the monkey immunogenicity conclusion as vague, noting the absence of neutralising antibodies appeared to apply to a different compound in the same study.

The regulatory record

FDA evaluated all five CJC-1295-related substances for the 503A bulk drug substances list and, in a memorandum dated 15 November 2024, proposed against adding any of them. The stated grounds were lack of clarity in physicochemical characterisation, insufficient information on historical compounding use, safety concerns from the nonclinical studies, absent clinical safety data for four of the five substances, and absent effectiveness data for all five in growth hormone deficiency. FDA also flagged aggregation and immunogenicity risk specific to injectable peptide preparations, and noted that a certificate of analysis supplied for one substance lacked tests for impurities, aggregates and endotoxins.

None of the five is an approved drug or a component of one, in the United States or elsewhere, and there is no United States Pharmacopeia or National Formulary monograph for any of them. FDA also observed that people with complete growth hormone deficiency would not respond to a secretagogue at all, which limits the indication the substances were nominated for. Under the World Anti-Doping Agency 2026 Prohibited List, CJC-1295 is named at section S2.2.4 among GHRH analogues, prohibited at all times, in and out of competition.

What has been found in the vials

Analytical chemistry laboratories have reported on material seized or submitted under the CJC-1295 name, and the results do not consistently match the molecule the trials used. Henninge and colleagues analysed an unknown pharmaceutical preparation submitted by Norwegian police and customs in 2009 and identified a 29-amino-acid peptide with a C-terminal amide, consistent with the peptide marketed as CJC-1295. Timms and colleagues, developing an equine detection assay, describe CJC-1295 as a 30-amino-acid peptide defined by its maleimidopropionic acid group. A 29-residue amidated peptide does not carry that group.

Gajda and colleagues examined preparations seized by Danish customs and identified modified GRF (1-29) alongside three growth hormone secretagogues, each carrying an extra glycine at the N-terminus. That modification was present in every case and was not declared. Their conclusion was that analytical methods needed updating to catch it, which is a statement about what is being distributed rather than about pharmacology.

A separate asymmetry runs through the whole file. FDA searched and found no pharmacological study, no pharmacokinetic study and no toxicology study of CJC-1295 free base or its acetate in any species. The tetrasubstituted 29-mer sold as the DAC-free version of this compound has never been characterised in a published experiment under that name. Every number that circulates about CJC-1295 was generated with the albumin-binding molecule, and the two are not interchangeable; FDA said so explicitly, and the pharmacology of a covalently modified peptide cannot be extrapolated to the unmodified one.

What is not known

Nothing is known about exposure beyond a few weeks in a person. The published human record consists of 42 subjects given a single dose, 24 given two or three doses over 14 days, and 12 given a single dose with overnight sampling, all healthy volunteers, 87 percent of them men by FDA's count. No trial has reported a clinical endpoint of any kind: no body composition, no functional measure, no disease outcome. The one study designed to produce such an endpoint was terminated in 2006 and its data have never been released, so the safety and effectiveness of twelve weeks of dosing in people with a condition remain unexamined. No published data address use in children, in pregnancy, in older adults, or in people with growth hormone deficiency, the indication for which the substance was nominated to FDA; a secretagogue would not be expected to work at all in complete deficiency. Carcinogenicity has never been studied, which matters because the one long-term rodent experiment on record found pituitary enlargement and DNA damage after eight weeks. Immunogenicity in humans has not been characterised. The DAC-free peptide sold under the same name has no published pharmacology whatsoever. And material circulating under either name has been found by forensic laboratories to differ from what the label says.

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