CJC-1295 and Gabapentin Interaction: What You Need to Know

CJC-1295: an unapproved peptide with limited human data

CJC-1295 is not FDA-approved [4]. In December 2024 FDA found no approved product containing any form of CJC-1295 in Australia, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Japan, Norway, Spain or the United Kingdom, and none authorized by the European Medicines Agency [4]. It is an investigational long-acting analogue of growth hormone-releasing hormone (GHRH) [4].

Two forms circulate under the name: a 29-amino-acid GHRH analogue, and CJC-1295 DAC, which is the same peptide with an extra unit at one end that lets it bind albumin in the blood and last much longer [4][6]. It acts on the pituitary like GHRH, raising the body's own growth hormone and, through it, IGF-I.

Because the DAC form binds albumin, its half-life is measured in days. After one subcutaneous injection in healthy adults, the estimated half-life was 5.8 to 8.1 days, mean growth hormone rose 2- to 10-fold for 6 days or more, and mean IGF-I rose 1.5- to 3-fold for 9 to 11 days [7]. Doses in the human studies were single subcutaneous injections of about 30 to 250 micrograms/kg, or two or three doses given weekly or every two weeks [4][7].

CJC-1295 is in none of the three categories on FDA's list for state-licensed pharmacies and physicians and is not on FDA's list for outsourcing facilities [8][9]. On December 4, 2024, FDA's Pharmacy Compounding Advisory Committee voted 0 yes and 13 no on CJC-1295 free base [10]. FDA also noted that CJC-1295 products sold online are mostly labeled research use only, which are not approved drugs [4].

Gabapentin: what is known about combining it with other drugs

Gabapentin is a prescription anticonvulsant first approved in 1993, labeled for postherpetic neuralgia in adults and as add-on therapy for partial-onset seizures in adults and children 3 years and older [11][3]. Neuropathic pain from diabetes, anxiety and sleep are off-label uses; Gralise and Horizant are separate gabapentin-based products [11].

Gabapentin is not metabolized by hepatic enzymes and does not inhibit them, and it is excreted renally with an elimination half-life of about 6 hours [2]. Its absorption is saturable: absolute bioavailability falls from 60% to 33% as the daily dose rises from 900 to 3600 mg, so blood levels do not climb in proportion to dose [2].

The interaction concern in gabapentin's labeling is additive central nervous system depression. FDA's 2019 communication says serious breathing difficulties can occur in people taking gabapentin who have respiratory risk factors, including opioid pain medicines, other CNS depressants, lung conditions such as COPD, and older age [3]. FDA advised prescribers to start at the lowest dose and monitor for respiratory depression and sedation when a gabapentinoid is co-prescribed with an opioid or another CNS depressant such as a benzodiazepine [3]. The symptoms FDA lists are confusion or disorientation, unusual dizziness, extreme sleepiness, slowed or shallow breathing, unresponsiveness and bluish skin [3].

Is there a pharmacokinetic interaction?

Gabapentin is not metabolized by liver enzymes and does not inhibit them [2]. CJC-1295 DAC is held in the blood by albumin binding, which the published work gives as the reason it lasts days rather than minutes [1]. Whether the two affect each other's levels has not been measured, so this is reasoning from how each drug is handled on its own.

Sedation and breathing: the labeled concern

Only gabapentin carries a labeled sedation and breathing warning. The Neurontin label reports respiratory depression and sedation, sometimes resulting in death, with gabapentin plus opioids, and FDA's communication extends the monitoring advice to other CNS depressants [3]. CJC-1295 is not named in that communication [3].

In the healthy-volunteer studies of CJC-1295 DAC, the recorded events included injection-site reactions (about 70% of treated subjects in the first trial and all treated subjects in the second), headache in 63% versus 14% on placebo in the first trial, flushing, warmth and transient low blood pressure in about 30% of treated subjects in the first trial, transient diarrhea, and transient dizziness and low blood pressure in two subjects [4][7]. In a separate study of healthy men given one dose, heart rate rose in a dose-dependent way [4]. Most events were more common at the higher doses, and no serious adverse reactions were reported in the two main trials [4][7].

FDA's broader concern about growth hormone-raising products is that the risks listed on approved growth hormone labels include glucose intolerance and diabetes, fluid retention and tumor growth concerns. FDA said the human CJC-1295 studies were short, small and mostly single-dose, so long-term safety is unknown [4].

Kidney function and gabapentin

Gabapentin leaves the body unchanged through the kidneys, and its clearance is proportional to creatinine clearance, which is reduced in older adults and in kidney impairment. The label sets lower maximum daily doses as creatinine clearance falls (for example 200 to 700 mg a day at a clearance above 15 to 29 mL/min) and says doses for older adults should be chosen by creatinine clearance. Kidney function affects gabapentin exposure regardless of what else a person takes.

What is known, and what is not

Known: gabapentin's handling and its labeled CNS-depressant warnings [2][3]; CJC-1295's regulatory status and thin human dataset [4]; and its recorded adverse events [7]. FDA's briefing also says ConjuChem withdrew CJC-1295 DAC from clinical trials in 2006 after a participant in a phase 2 trial in HIV lipodystrophy (192 enrolled) died. FDA cites news reports that the person had chest discomfort 2 hours after an 11th weekly dose and an ECG showing an acute heart attack, with the attending physician's most likely explanation being undiagnosed coronary artery disease with plaque rupture. The data were never published, so a causal link is neither shown nor excluded [4].

Not known: whether CJC-1295 changes gabapentin's effects or levels. FDA identified only three published human studies of CJC-1295, all of the DAC form and all in healthy volunteers, and found no study of any form in people with a disease [4]. An interaction that has not been studied is not the same as an interaction that has been ruled out.