CJC-1295 with DAC

CJC-1295 is a tetrasubstituted analog of growth hormone-releasing hormone (GHRH). It exists in two forms: CJC-1295 with DAC (Drug Affinity Complex), which uses an albumin-binding modification to extend half-life to roughly one week, and CJC-1295 without DAC (also called modified GRF 1-29 or Mod-GRF), which has a half-life of about 30 minutes. Both versions activate the GHRH receptor on pituitary somatotrophs and trigger growth-hormone release.

The base molecule is the same as sermorelin: a 29-amino-acid peptide corresponding to the receptor-binding domain of native GHRH. The four substitutions, at positions 2, 8, 15, and 27, protect the peptide from enzymatic degradation. The result is a "modified GRF 1-29" that resists DPP-IV cleavage and has a substantially longer half-life than sermorelin.

The DAC addition is a separate modification. The Drug Affinity Complex is an N-3-maleimidopropionamide derivative of lysine attached at the C-terminus. It binds covalently to serum albumin, extending circulation time from minutes to days. With DAC, CJC-1295 produces sustained GH and IGF-1 increase across roughly a week. Without DAC, the modified-GRF form has the short pulsatile profile that more closely resembles physiological GH release.

The molecule was developed by ConjuChem Biotechnologies in the early 2000s under the codes CJC-1295 and CJC-1131. ConjuChem ceased operations in 2010. The compound has had no commercial sponsor since. Every batch of "CJC-1295" sold today is synthesized by research-chemical or specialty peptide suppliers without the pharmaceutical development infrastructure that produced the original Phase 1 dataset.

The Published Human Evidence

Two trials make up the published human evidence base for CJC-1295.

Teichman et al., JCEM, 2006. The pivotal Phase 1 trial in healthy subjects aged 21 to 61. Two randomized, placebo-controlled, double-blind, ascending-dose studies with durations of 28 and 49 days. CJC-1295 with DAC was administered subcutaneously in one of four ascending single doses in the first study and in two or three weekly or biweekly doses in the second study. Key findings: dose-dependent increase in plasma GH of 2 to 10 times baseline for 6 days or more, IGF-1 increase of 1.5 to 3 times baseline for 9 to 11 days, half-life of 5.8 to 8.1 days, sustained IGF-1 increase above baseline for up to 28 days after multiple doses, and no serious adverse reactions reported.

Limited additional human data. ConjuChem published one earlier Phase 1 study in growth hormone-deficient adults and several preclinical reports. No Phase 2 efficacy trial in any indication was completed before the company shut down.

For comparison, sermorelin has multiple human trials including the pediatric Phase 3 program that supported its 1997 FDA approval. Tesamorelin has more than 800 patients in published Phase 3 trials. CJC-1295 has a few dozen subjects across two Phase 1 studies, no Phase 2 program, and no Phase 3 data. This is the smallest published human evidence base of any GHRH analog in widespread compounding use.

CJC-1295 activates the GHRH receptor with the same downstream effects as sermorelin and tesamorelin. The differentiation is pharmacokinetic, not mechanistic.

GHRH receptor activation on pituitary somatotrophs triggers GH release through the standard G-protein coupled receptor cascade involving cAMP, protein kinase A, and intracellular calcium. The pituitary stores releasable GH in secretory granules that are emptied in pulses lasting roughly 30 to 90 minutes. The system is rate-limited by how much GH the pituitary can produce and store.

This is where the DAC variant's pharmacology gets complicated. CJC-1295 with DAC produces continuous GHRH receptor stimulation for days. The pituitary cannot maintain continuous GH output at supraphysiological levels indefinitely. Reported Phase 1 data showed sustained GH increase, but the long-term consequences of continuous receptor activation, including potential receptor desensitization and disruption of normal pulsatile patterns, have not been characterized in published human trials.

CJC-1295 without DAC behaves more like a long-acting sermorelin. The 30-minute half-life produces a discrete GH pulse with each injection and allows the natural pulsatile pattern to recover between doses. This is the version most commonly stacked with ipamorelin in clinical compounding settings.

This compound is on the World Anti-Doping Agency (WADA) Prohibited List. Use in competitive sport, in-competition or out-of-competition, constitutes an anti-doping rule violation.

Phase 1 Trial Outcomes (Teichman 2006)

The only published Phase 1 trial of CJC-1295 with DAC documented a specific and consistent pharmacological profile in healthy adults aged 21 to 61.

Plasma GH increase. Dose-dependent increase of 2 to 10 times baseline for 6 days or more after a single subcutaneous injection. The magnitude was larger than what sermorelin produces and is broadly comparable to tesamorelin daily dosing summed across a week.

IGF-1 increase. 1.5 to 3 times baseline, sustained for 9 to 11 days after a single injection. With multiple weekly or biweekly doses, IGF-1 remained elevated above baseline for up to 28 days. This is the longest-duration IGF-1 elevation produced by any GHRH analog in published human data.

Half-life. 5.8 to 8.1 days, the longest of any peptide currently used in compounding settings. The extended half-life is mediated by covalent albumin binding via the maleimide DAC linker.

Safety. No serious adverse reactions in the 49-day follow-up. The study population was small (a few dozen subjects across both ascending-dose protocols) and the duration was limited.

The trial did not test any specific therapeutic indication. It was a pharmacokinetic and pharmacodynamic characterization study. No endpoint relevant to body composition, sleep, recovery, or other off-label use cases was measured.

Off-Label Subjective Effects

Adult off-label users in compounded settings have reported a consistent pattern of subjective effects, though none has Phase 2 or Phase 3 trial validation.

Improved sleep quality. Reported within the first 1 to 2 weeks of use. The mechanistic basis is plausible given GH-sleep architecture coupling, but the continuous receptor activation profile of CJC-1295 with DAC may produce a different pattern than the pulsatile profile of sermorelin or no-DAC CJC-1295.

Recovery and body composition. Subjective reports of reduced soreness and modest body composition changes over 3 to 6 months of use. Effects are difficult to separate from concurrent training and nutrition in uncontrolled use.

Skin elasticity and hair quality. Reported anecdotally in cosmetic-medicine settings. Observational rather than controlled.

The honest summary is that CJC-1295 with DAC produces measurable IGF-1 increase per the Teichman 2006 trial, with downstream subjective effects that are biologically plausible but unvalidated at trial scale.

The Continuous Receptor Activation Question

A specific scientific concern attaches to CJC-1295 with DAC that does not apply to short-acting GHRH analogs.

Native GHRH is released in pulses every 3 to 5 hours. The pulsatile pattern is essential for normal GH secretion dynamics. Continuous GHRH receptor activation across days, which is what CJC-1295 with DAC produces, may produce receptor desensitization, altered pituitary somatotroph function, and disrupted normal pulsatile GH release. None of these has been characterized in long-term human trials.

The Teichman 2006 study followed subjects for 49 days. It documented sustained GH and IGF-1 elevation. It did not test what happens with continuous use over months or years. The compound has been in compounded clinical use for nearly two decades without published long-term follow-up data, which is the central knowledge gap in the CJC-1295 evidence base.

Teichman 2006 Trial Doses

The pivotal Phase 1 trial tested specific weight-based doses.

Single-dose study: 30, 60, 90, and 250 mcg/kg subcutaneously, ascending-dose design. For a 75 kg adult, these correspond to approximately 2.25 mg, 4.5 mg, 6.75 mg, and 18.75 mg per dose.

Multiple-dose study: 60 mcg/kg (about 4.5 mg in a 75 kg adult) administered weekly or biweekly, or 125 mcg/kg (about 9.4 mg) administered biweekly. Trial duration was 49 days, encompassing several weekly or biweekly injections.

The doses tested in Phase 1 were considerably higher than the doses used in adult off-label compounded settings. No clinical efficacy endpoint was tested at any dose. The trial established pharmacokinetic and basic pharmacodynamic profiles without testing what dose produces optimal therapeutic effect.

Adult Off-Label Compounded Protocols

Adult off-label CJC-1295 with DAC protocols used in compounding settings before the September 2023 Category 2 placement typically fell in the following ranges.

Standalone dosing: 1 to 2 mg subcutaneously once or twice weekly, regardless of body weight. The fixed-dose approach (rather than weight-based) is the typical compounding pattern. Twice-weekly dosing produces a smoother IGF-1 profile across the week than once-weekly dosing.

Stack with ipamorelin: 1 to 2 mg of CJC-1295 with DAC weekly plus 100 to 300 mcg of ipamorelin daily, both subcutaneous. The asymmetric dosing reflects the dramatically different half-lives of the two compounds. CJC-1295 with DAC sustains weekly GHRH receptor activation. Ipamorelin produces daily ghrelin receptor pulses on top of that sustained signal.

The 1 to 2 mg weekly compounded dose is below the 60 to 125 mcg/kg range tested in Phase 1. Whether this is the optimal clinical dose is unknown. The lower compounded dose appears to reflect clinical practice considerations (cost, tolerability, IGF-1 monitoring) rather than evidence-based titration.

Why Compounded Dosing Falls Below Phase 1 Range

The Teichman 2006 doses (60 to 125 mcg/kg, approximately 4.5 to 9.4 mg in a 75 kg adult) produced IGF-1 increases of 1.5 to 3 times baseline, well above the age-adjusted upper limit of normal in many subjects. Sustained IGF-1 increase substantially above the age-adjusted normal range is associated epidemiologically with cancer risk and is a flag for monitoring. Adult off-label compounding protocols at 1 to 2 mg weekly likely produce IGF-1 increases of approximately 20 to 50 percent above baseline, which keeps most patients within or near the upper quartile of the age-adjusted normal range rather than substantially above it. The lower compounded dose is plausibly safer for sustained use, even though it has not been formally validated in a Phase 2 trial.

Pharmacokinetics

CJC-1295 with DAC has a plasma half-life of approximately 5.8 to 8.1 days after subcutaneous injection. Peak GH response occurs within hours to 1 day after injection. The sustained albumin-bound peptide produces continuous GHRH receptor signaling, which differentiates the pharmacological profile from any of the short-acting GHRH analogs.

Steady-state IGF-1 response builds over 2 to 4 weeks of weekly dosing. Discontinuation produces IGF-1 return toward baseline over 2 to 4 weeks, reflecting the long half-life. Dose changes take approximately a month to fully take effect.

Stack Dose Ratios with Ipamorelin

The CJC-1295 with DAC plus ipamorelin combination uses asymmetric dosing because the half-lives differ by orders of magnitude.

CJC-1295 with DAC: 1 to 2 mg once or twice weekly. The dose covers a full 6 to 8 day exposure window.

Ipamorelin: 100 to 300 mcg subcutaneously daily, typically before bed. The daily pulse adds ghrelin receptor signaling to the sustained GHRH signal.

The asymmetric protocol contrasts with the symmetric CJC-1295 (no DAC) + ipamorelin stack, where both compounds are dosed daily at similar microgram amounts. The choice between symmetric (no DAC) and asymmetric (with DAC) stacks usually reflects convenience preference rather than trial-based comparison.

Reconstitution

CJC-1295 with DAC is supplied as lyophilized powder, typically in 2 mg or 5 mg vials. Reconstitution with bacteriostatic water is standard. Once reconstituted, the peptide is stable for 4 to 8 weeks refrigerated. The maleimide DAC linker is sensitive to reducing agents (such as dithiothreitol or beta-mercaptoethanol), which would cleave the albumin-binding bond and abolish the pharmacokinetic advantage. Standard reconstitution and storage conditions do not present these reducing agents.

The Teichman 2006 Phase 1 trial reported no serious adverse reactions across the 49-day follow-up. The most common adverse events were transient injection-site reactions, mild flushing, and headache. The study population was small and the follow-up was short.

Beyond that single trial, the safety profile for CJC-1295 is inferred from class effects of GHRH receptor stimulation. Expected adverse events at therapeutic doses include the same effects seen with sermorelin and tesamorelin: injection-site reactions, peripheral edema, mild glucose increase, theoretical IGF-1-related risks, and carpal tunnel syndrome at higher doses or in susceptible patients.

The specific concern for CJC-1295 with DAC is the sustained receptor activation profile. Most physiological hormone systems are pulsatile for evolutionary reasons related to receptor sensitivity and downstream signaling. Continuous GHRH receptor stimulation across days may produce receptor desensitization, altered GH secretory dynamics, or sustained supraphysiological IGF-1 levels. None of these has been characterized in long-term human trials.

The FDA Category 2 designation cited insufficient safety data as the basis for restriction. The compound was not flagged for documented harm. That distinction matters: the agency is saying the safety database is too thin to support compounding, not that the molecule has caused specific adverse events.

The two versions are not interchangeable, and most online discussion conflates them.

CJC-1295 with DAC is the long-acting form. Once or twice weekly subcutaneous injection. Sustained GH and IGF-1 increase across the week. Produces continuous GHRH receptor activation rather than physiological pulses. The Phase 1 evidence base above refers to this form.

CJC-1295 without DAC (modified GRF 1-29, Mod-GRF, "Mod-GRF 1-29") is the short-acting form. Daily subcutaneous injection, often split into multiple smaller doses per day. Produces a discrete GH pulse with each injection that decays within an hour. No human pharmacokinetic trial of the no-DAC form has been published. The dosing protocols used in compounding settings are extrapolated from sermorelin data and from the early CJC-1295 with DAC trial.

In practice, the no-DAC form is more commonly prescribed in compounded settings because it preserves physiologic pulsatility. The DAC form is preferred when convenience or sustained IGF-1 increase is the goal. Both are typically combined with ipamorelin to produce a stronger GH pulse than either compound alone, exploiting the synergy between GHRH receptor activation and ghrelin receptor activation.

For informational and educational purposes only. Not medical advice. Not for human consumption unless prescribed by a licensed physician for an FDA-approved indication. Consult a qualified healthcare provider before using any peptide or pharmaceutical product.