CJC-1295 vs Sermorelin – two GHRH analogs on opposite sides of the regulatory line

Sermorelin Acetate and CJC-1295 with DAC are the same idea executed twenty years apart: take growth hormone–releasing hormone, keep the part that works, and ask the pituitary to release its own growth hormone rather than injecting the hormone itself. They are built on the same 29-amino-acid backbone and act at the same receptor. What separates them is not biology. It is that one of them completed the regulatory process and the other never did. This page is educational and does not recommend either compound or any protocol.

Head-to-head

One parent sequence, two engineering answers

Sermorelin is GHRH(1-29): an amino acid composition identical to the N-terminal 29 residues of the natural hypothalamic hormone GHRH(1-44), with nothing added. That fidelity is also its commercial weakness. Its plasma half-life in humans is roughly 10 to 20 minutes, limited mostly by renal ultrafiltration and enzymatic degradation at the N-terminus (Esposito et al., Adv Drug Deliv Rev 2003). Twice-daily injection was the price of using the unmodified molecule.

CJC-1295 is what happens when a company sets out to fix that number. ConjuChem started with the same fragment, substituted four residues to block the known degradation routes — D-alanine at position 2 resists dipeptidyl peptidase-IV, glutamine at 8 avoids asparagine rearrangement, leucine at 27 avoids methionine oxidation — and then added a maleimido-lysine at the C-terminus. After injection that group reacts with the free thiol on cysteine-34 of circulating serum albumin, so the peptide travels bound to albumin instead of being cleared. In rats the conjugate produced a four-fold larger GH area under the curve than unmodified hGRF(1-29) and was still present in plasma beyond 72 hours (Jetté et al., Endocrinology 2005). In healthy adults, a single subcutaneous dose raised mean GH 2- to 10-fold for six days or more and IGF-1 1.5- to 3-fold for 9–11 days; the estimated half-life was 5.8 to 8.1 days (Teichman et al., J Clin Endocrinol Metab 2006).

The engineering worked. Minutes became days. Whether a week of continuously elevated growth hormone is physiologically equivalent to a nightly pulse is a separate question, and one nobody has tested in either direction.

The regulatory line

Sermorelin was an approved drug — the only compound in this family that ever was. FDA approved Geref under NDA 019863 on 28 December 1990 at 0.05 mg per ampoule as a GHRH stimulation test, and under NDA 020443 on 26 September 1997 at 0.5 mg and 1 mg per vial, with orphan designation, to treat short stature in children with idiopathic GH deficiency. Both are now discontinued, and Drugs@FDA records against each one the Federal Register determination that the product “was not discontinued or withdrawn for safety or effectiveness reasons.” A review from the period gives the commercial reading directly: sermorelin “could not compete with rhGH and was withdrawn as a therapeutic entity by the manufacturer” (Walker, Clin Interv Aging 2006).

CJC-1295 never got that far. Its only trial in people with a condition — a phase 2 study of HIV-associated visceral obesity run by ConjuChem — is registered as terminated (NCT00267527). Two hours after an eleventh weekly dose, a participant reported chest discomfort; an ECG confirmed acute myocardial infarction and he died about an hour later. The attending physician’s stated most likely explanation was asymptomatic coronary artery disease with plaque rupture and occlusion — a hypothesis, not a resolved cause. The trial was stopped and its data were never published, which is why FDA’s own account of the event is reconstructed from contemporaneous news reports rather than from a study report (FDA briefing document, PCAC December 2024). The registry lists 120 participants; the reports FDA cites describe 192 randomized. Both figures are in the public record, and nothing exists to reconcile them.

In December 2024 FDA asked its Pharmacy Compounding Advisory Committee whether any CJC-1295 form belonged on the 503A bulk drug substances list. The committee voted against all five: 13–0 against CJC-1295 free base, 12–1 against CJC-1295 acetate, and 13–0 against each of CJC-1295 DAC free base, DAC acetate and DAC trifluoroacetate (PCAC final summary minutes, 4 December 2024).

What the human evidence actually shows

Sermorelin’s clinical record is small but real, and it includes a direct comparison it loses. In nine children with radiation-induced GH deficiency, GHRH(1-29) at 15 µg/kg twice daily raised height velocity from 3.3 to 6.0 cm/year over a year; the same children switched to growth hormone the following year grew 7.5 cm/year (Ogilvy-Stuart et al., Clin Endocrinol 1997). The most-cited adult study used a close relative rather than sermorelin itself: 19 adults aged 55–71 received [Nle²⁷]GHRH(1-29)-NH₂ at 10 µg/kg nightly for 16 weeks. IGF-1 rose within two weeks, skin thickness increased in both sexes and lean body mass increased in men — but sleep quality was unaffected in both groups, which is the opposite of the claim the study is usually recruited to support (Khorram et al., J Clin Endocrinol Metab 1997).

Every published human study of CJC-1295 was a pharmacokinetic study in healthy volunteers. FDA counted 63 healthy adults across all of them, 87% men, at doses from 30 to 250 µg/kg, and concluded there are “no studies evaluating effectiveness in humans with GHD for any of the evaluated substances.” The compound raises IGF-1; that is not in dispute. Whether raising IGF-1 this way helps anyone with anything has not been studied.

One asymmetry is worth naming. Both compounds ask a pituitary to release growth hormone, so neither helps a pituitary that cannot. Geref’s label handled this explicitly, restricting treatment to children who first passed a Geref stimulation test and instructing that those with a peak GH below 2 ng/mL “should be excluded from Geref therapy.” Nothing in the CJC-1295 literature addresses which patients would or would not respond.

“CJC-1295” does not name a molecule

This is the practical difference that matters most, and it has nothing to do with efficacy. Sermorelin acetate is a defined active ingredient with an approval history. “CJC-1295” is a label that FDA found attached to five chemically distinct substances: CJC-1295 free base, CJC-1295 acetate, CJC-1295 DAC free base, CJC-1295 DAC acetate and CJC-1295 DAC trifluoroacetate. FDA judged the group “not well characterized” because of inconsistent naming conventions, and — the part that should stop any reader short — said that even for the published human studies “it is unclear which substance was used,” with no salt form specified.

The two ends of that range are a peptide whose parent clears in 10–20 minutes and one that persists for the better part of a week: a gap of roughly three orders of magnitude, hiding behind a single product name. FDA also stated that it could not identify studies establishing whether the free base is pharmacologically active at all, and that the DAC version’s pharmacology cannot be extrapolated to the version without it. A vial reading “CJC-1295” is therefore not a dose, a duration, or in any strict sense an identification.

Safety signals on the record

Neither compound has long-term human safety data outside its labeled history, and both act on the GH/IGF-1 axis, which carries the usual theoretical concerns about glucose metabolism, fluid balance and tissue growth. What distinguishes CJC-1295 is that specific signals were logged and then never followed up. In Teichman’s first study, adverse events occurred in 33 of 35 subjects (94%) on active drug versus 2 of 7 (29%) on placebo: injection-site reactions in about 70%, transient urticarial rashes at the injection site in almost 30%, headache in 63% (vs 14% placebo), diarrhea in 43%, and vasodilatory flushing in 30%. Separately, FDA’s review cites work in which CJC-1295 DAC produced DNA damage in mouse pituitary cells by Comet assay and raised γH2AX expression, with eight weeks of dosing in mice increasing relative anterior pituitary weight and pituitary DNA damage. FDA noted no comparable genotoxicity data exist for the free base forms at all.

Sermorelin’s reported effects in its clinical record run to injection-site reactions, flushing and headache. The meaningful point is not that one compound is gentle and the other is not — it is that one accumulated a pharmacovigilance record under a label and the other stopped generating data in 2006.

Anti-doping

Here the two converge completely. WADA’s prohibited list names both under section S2.2.4, growth hormone releasing factors, covering “growth hormone-releasing hormone (GHRH) and its analogues (e.g. CJC-1293, CJC-1295, sermorelin and tesamorelin)” (WADA 2026 Prohibited List). Prohibited at all times, in and out of competition. Approval status is irrelevant to that determination — ipamorelin and the ghrelin agonists sit in the same section for the same reason.

How to dive deeper

• Sermorelin Acetate overview · research · side effects
• CJC-1295 with DAC overview · research
• CJC-1295 without DAC (modified GRF 1-29) overview
• Ipamorelin — the ghrelin-receptor agonist both are commonly paired with
• Why do some doctors not prescribe peptides? · What are the risks of peptides? · What are peptides?
• More side-by-sides: compare hub