CJC-1295 side effects: the human record, dose by dose

Which CJC-1295 the question is about

Every human safety datum for "CJC-1295" belongs to the albumin-bound form, the one with the DAC linker and the 5.8 to 8.1-day half-life. The linker-free form that fills most research vials, Mod GRF 1-29, has never been given to people in a published study. So the trial data below describe a molecule that is present for a week; the class data, from GHRH itself and from sermorelin, describe molecules that are present for minutes, which is the better match for the blend. The distinction is explained in DAC versus no DAC; keep it in mind for every sentence that follows.

What the two trials recorded

Teichman and colleagues ran two randomized, double-blind, placebo-controlled ascending-dose studies in healthy adults aged 21 to 61, one of 28 days after single doses and one of 49 days after two or three weekly or biweekly doses. Their abstract reports the safety outcome in two sentences: "No serious adverse reactions were reported", and the peptide "was safe and relatively well tolerated, particularly at doses of 30 or 60 µg/kg" [Teichman et al., 2006].

The qualifier is informative: at the higher single doses tolerability was evidently less good, though the abstract does not say in what way. Ionescu and Frohman's pulsatility study, in men aged 20 to 40 at 60 or 90 µg/kg, reports hormonal outcomes and no adverse-event data [Ionescu et al., 2006]. That is the complete published human safety record: two small trials, weeks long, in healthy volunteers, with no itemised adverse-event table in the public abstracts.

Swipe sideways to see the whole table.

Class effects: flushing and the injection site

What a GHRH-receptor agonist does besides releasing GH is well documented for the parent hormone and for sermorelin. In Bowers' 1990 study, GHRH(1-44) at 1 µg/kg produced mild facial flushing lasting one to three minutes in 16 of 18 men, while GHRP-6 did not [Bowers et al., 1990]. In the sermorelin programme reviewed by Prakash and Goa, the most frequently reported adverse events with once-daily subcutaneous dosing in children were transient facial flushing and pain at the injection site [Prakash et al., 1999].

In Corpas' 14-day study of twice-daily GHRH(1-29) in men aged 68, the treatment did not affect fasting glucose, urinary C-peptide, blood pressure, or chemistry and haematology profiles; serum phosphate rose, as it does with GH [Corpas et al., 1992]. Flushing is the signature of the receptor, and any CJC-1295 form should be expected to share it; injection-site reactions are the signature of injecting a peptide, and the albumin-binding maleimide of the DAC form is a plausible additional local irritant, though no study quantifies it.

The IGF-1 question

The effect people worry about is not a side effect in the usual sense but the intended effect sustained. One CJC-1295 dose raised IGF-1 1.5 to 3-fold for 9 to 11 days, and after repeated doses IGF-1 stayed above baseline for up to 28 days [Teichman et al., 2006]; a week after one dose, trough GH was 7.5-fold higher and IGF-1 45 % higher [Ionescu et al., 2006]. Chronic elevation of GH and IGF-1 is the defining feature of acromegaly, and it is why the pulsatile pattern of GH is thought to matter.

The Ionescu study is reassuring on one point, the pulses survived, and silent on the other, what months of a raised trough do, because nobody has looked. In GHRH-knockout mice, five weeks of daily CJC-1295 increased pituitary GH mRNA and the number of somatotroph cells [Alba et al., 2006]; that is the expected trophic effect of GHRH on its target cells, and whether it has any human counterpart at the doses studied is unknown.

Glucose, by way of tesamorelin

Raising GH raises hepatic glucose output, so glucose is the metabolic variable to watch with any secretagogue. The CJC-1295 trials do not report it. The best available measurement is for tesamorelin, the GHRH analogue that finished its programme. In 412 HIV patients treated for 26 weeks, glycaemic measures did not differ from placebo, although more patients on tesamorelin withdrew because of an adverse event [Falutz et al., 2007].

In 50 patients treated for 6 months, fasting glucose rose 9 mg/dl at 2 weeks against 2 mg/dl on placebo (P = .03), and by 6 months the difference was no longer significant [Stanley et al., 2014]. An early, modest, transient rise in fasting glucose is therefore the documented pattern for a daily GHRH analogue in patients; CJC-1295, with a week-long half-life, has no equivalent measurement, and the comparison is drawn out in CJC-1295 ipamorelin versus tesamorelin.

What was never studied

• Exposure beyond 49 days in humans.
• Any patient population: the ConjuChem phase 2 in HIV-associated visceral obesity was terminated in 2006 without results [ConjuChem, 2005].
• Glucose, insulin, lipids, blood pressure or fluid retention on CJC-1295.
• The linker-free form, at any dose, for any duration.
• CJC-1295 combined with ipamorelin or any GHRP.
• Immunogenicity of the albumin conjugate, the concern the FDA raised for ipamorelin in 2023.

The regulatory record

CJC-1295 is not an approved drug anywhere. It was nominated for the FDA's list of bulk substances usable in compounding, and the nomination appears among those subsequently withdrawn on the FDA page that lists substances that "may present significant safety risks"; ipamorelin acetate, its usual partner, was placed in category 2 of that list on September 29, 2023 with an immunogenicity concern [U.S., 2023]. The WADA Prohibited List names CJC-1295 among GHRH analogues in class S2 [World, 2026]. For the other half of the pair, see ipamorelin side effects.

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