CJC-1295: GHRH Analog Research Profile

CJC-1295 represents a significant advancement in peptide pharmacology — a synthetic analog of growth hormone-releasing hormone (GHRH) engineered to overcome the limitations of native GHRH's seven-minute half-life. Originally developed by ConjuChem Biotechnologies for treating growth hormone deficiency and lipodystrophy, this 30-amino acid peptide incorporates strategic molecular modifications that extend its biological activity from minutes to days.

The peptide exists in two distinct forms, each with fundamentally different pharmacokinetic profiles: CJC-1295 with Drug Affinity Complex (DAC), which binds covalently to serum albumin and maintains elevated growth hormone levels for up to a week, and CJC-1295 without DAC — more accurately called Modified GRF (1-29) — which preserves the body's natural pulsatile growth hormone release pattern with a 30-minute half-life.

Despite reaching Phase II clinical trials and demonstrating dose-dependent increases in growth hormone (2- to 10-fold) and IGF-1 (1.5- to 3-fold) levels, CJC-1295 was never approved by the FDA. Clinical development ceased following a study participant's death, and the peptide remains prohibited for compounding under current FDA regulations. Yet it persists in research contexts and off-label clinical use, often paired with ipamorelin to create synergistic effects on the growth hormone axis.

Quick Facts
What Is CJC-1295?
Molecular Structure and Modifications
How CJC-1295 Works: Mechanisms of Action
Pharmacokinetics: Understanding the DAC Difference
Research Evidence
CJC-1295 and Ipamorelin: The Popular Combination
CJC-1295 vs. Other GHRH Analogs
Safety Profile and Side Effects
Legal and Regulatory Status
Frequently Asked Questions
The Bottom Line

Quick Facts

Attribute	Details
Full Name	CJC-1295 (with or without Drug Affinity Complex)
Other Names	Modified GRF (1-29), Mod GRF 1-29 (without DAC); CJC-1295 DAC (with DAC)
Peptide Type	Synthetic GHRH analog, growth hormone secretagogue
Amino Acid Length	30 amino acids
Molecular Weight	~3647 Da (with DAC); ~3367 Da (without DAC)
Half-Life	6-8 days (with DAC); 30 minutes to 2 hours (without DAC)
Mechanism	GHRH receptor agonist on pituitary somatotrophs
Primary Effects	Sustained GH and IGF-1 elevation
FDA Status	Not approved; prohibited for compounding
Clinical Status	Phase II discontinued
Administration	Subcutaneous injection

What Is CJC-1295?

CJC-1295 is a synthetic analog of growth hormone-releasing hormone, the hypothalamic peptide that signals the anterior pituitary to release growth hormone. Native GHRH (1-29) has a biological half-life of less than seven minutes, rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-IV) and susceptible to oxidation and deamidation. These limitations make natural GHRH impractical for therapeutic use.

CJC-1295 addresses these shortcomings through four strategic amino acid substitutions at positions 2, 8, 15, and 27, creating a tetrasubstituted analog with dramatically improved stability. The version "with DAC" includes an additional modification — a lysine residue conjugated to maleimidoproprionic acid (MPA) — that enables covalent binding to circulating albumin, further extending its duration of action.

The Two Versions: A Critical Distinction

CJC-1295 with DAC features a drug affinity complex that binds to serum albumin after injection, creating a slow-release depot effect. This version maintains elevated growth hormone levels continuously for 6-8 days from a single injection, effectively providing sustained baseline GH elevation rather than mimicking natural pulsatile release.

CJC-1295 without DAC, more accurately called Modified GRF (1-29), lacks the albumin-binding modification. With a half-life of approximately 30 minutes — significantly longer than native GHRH's seven minutes but far shorter than the DAC version — it produces sharp, transient spikes in growth hormone that return to baseline within 2-3 hours, closely mimicking the body's natural pulsatile GH secretion pattern.

This distinction matters. The DAC version provides continuous stimulation but may suppress natural GH pulsatility over time. The non-DAC version preserves physiological rhythms but requires multiple daily administrations. Neither naming convention is universally consistent in research literature or clinical practice, leading to significant confusion about dosing protocols and expected effects.

Molecular Structure and Modifications

Understanding CJC-1295's structure reveals why it performs differently from native GHRH and why the two versions have such divergent pharmacokinetic profiles.

Base Structure: Modified GRF (1-29)

The foundation of CJC-1295 is a 29-amino acid sequence derived from the biologically active portion of human GHRH (1-29), also known as sermorelin. The amino acid sequence of Modified GRF (1-29) is:

Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH₂

Four strategic substitutions differentiate this from native GHRH:

Position 2: Alanine → D-Alanine Substituting L-alanine with its D-isomer (mirror image) creates a peptide bond between D-Ala and aspartic acid (position 3) that resists rapid cleavage by DPP-IV. This single change extends the half-life from less than 10 minutes to approximately 30 minutes.

Position 8: Asparagine → Glutamine Asparagine residues are prone to deamidation and isomerization under physiological conditions. Replacing asparagine with glutamine eliminates this instability, preventing rearrangement to aspartic acid that would reduce receptor binding affinity.

Position 15: Glycine → Alanine This substitution improves bioactivity and receptor binding affinity, increasing the peptide's potency at GHRH receptors on pituitary somatotrophs.

Position 27: Methionine → Leucine Methionine is susceptible to oxidation, which degrades the peptide and reduces activity. Leucine is chemically stable and maintains the peptide's integrity in circulation.

These four modifications transform native GHRH into Modified GRF (1-29) — a significantly more stable and potent GHRH receptor agonist.

The DAC Modification

CJC-1295 with DAC adds a 30th amino acid (lysine) conjugated to maleimidoproprionic acid (MPA). This reactive group at the C-terminus enables covalent binding to circulating serum albumin through a maleimide-thiol reaction with cysteine residues on albumin molecules.

This albumin binding serves multiple functions:

Protection from degradation: Albumin-bound peptides are shielded from proteolytic enzymes
Extended circulation time: Albumin's 19-day half-life creates a slow-release depot
Sustained bioavailability: The peptide dissociates gradually from albumin, maintaining therapeutic levels

Research shows that CJC-1295 DAC binds covalently to circulating albumin after injection in animal models, resulting in a half-life of 5.8-8.1 days in humans compared to 30 minutes for the non-DAC version.

How CJC-1295 Works: Mechanisms of Action

CJC-1295 operates through the same fundamental pathway as endogenous GHRH, but with dramatically extended duration and, in some formulations, altered release patterns.

GHRH Receptor Activation

When administered, CJC-1295 binds to GHRH receptors located on somatotroph cells within the anterior pituitary gland. These receptors are G-protein-coupled receptors (GPCRs) that, upon activation, trigger intracellular signaling cascades:

Receptor engagement: CJC-1295 binds to the GHRH receptor with equal or greater affinity than native GHRH
G-protein activation: The activated receptor stimulates G-protein subunits (primarily Gαs)
Second messenger production: Activated G-proteins stimulate adenylyl cyclase, increasing cyclic AMP (cAMP) and inositol trisphosphate (IP3)
Calcium mobilization: Elevated cAMP and IP3 increase intracellular calcium concentration
Growth hormone secretion: Calcium influx triggers exocytosis of growth hormone-containing vesicles

This process is identical to natural GHRH signaling. What differs is the duration and pattern of receptor stimulation.

Effects on Growth Hormone Pulsatility

One particularly interesting finding from clinical research is that CJC-1295 with DAC does not appear to alter the frequency or amplitude of GH secretory pulses. Instead, it elevates basal (trough) growth hormone concentrations while preserving the normal pulsatile pattern.

This means CJC-1295 raises the baseline level of circulating GH between pulses rather than creating larger or more frequent peaks. The body's natural growth hormone pulses — which typically occur 6-8 times daily, with the largest pulse during deep sleep — continue on their normal schedule, but they rise from and return to a higher baseline.

This preservation of pulsatility may be physiologically important, as continuous non-pulsatile GH administration (as with traditional growth hormone replacement therapy) can lead to receptor desensitization and altered metabolic effects compared to physiological pulsatile secretion.

The IGF-1 Cascade

Growth hormone released from the pituitary exerts many of its effects through insulin-like growth factor 1 (IGF-1), primarily produced in the liver. Clinical studies demonstrate that CJC-1295 administration leads to sustained increases in IGF-1:

Single injection: 1.5- to 3-fold increase in IGF-1 for 9-11 days
Multiple doses: IGF-1 levels remain elevated for up to 28 days

IGF-1 mediates many of growth hormone's anabolic effects, including muscle protein synthesis, bone growth, and metabolic regulation. The sustained IGF-1 elevation produced by CJC-1295 differs from the more transient effects of shorter-acting GHRH analogs like sermorelin.

Comparison to Other Growth Hormone Secretagogues

CJC-1295 works through the GHRH receptor pathway, which is distinct from ghrelin mimetics like ipamorelin, GHRP-2, and GHRP-6. These compounds stimulate GH release through the ghrelin receptor (growth hormone secretagogue receptor 1a), which operates through a different intracellular signaling mechanism.

When combined, GHRH analogs and ghrelin mimetics produce synergistic effects — the two pathways activate somatotrophs through complementary mechanisms, resulting in GH release greater than the sum of either compound alone. This synergy forms the rationale for combination protocols pairing CJC-1295 with ipamorelin or other growth hormone-releasing peptides.

Pharmacokinetics: Understanding the DAC Difference

The pharmacokinetic profiles of CJC-1295 with and without DAC differ so dramatically that they function almost as distinct compounds with different clinical applications.

CJC-1295 with DAC

Half-Life: 5.8-8.1 days

Administration: Once weekly or less frequently

Mechanism of Extended Release: Covalent binding to serum albumin creates a circulating reservoir. The peptide gradually dissociates from albumin over several days, maintaining therapeutic concentrations.

Growth Hormone Pattern: Elevated basal GH levels with preserved pulsatility. Baseline GH increases by 2- to 10-fold for six or more days after a single injection.

IGF-1 Profile: Sustained elevation (0.5- to 3-fold increase) persisting for 9-11 days after single dose; up to 28 days with multiple doses.

Dosing Considerations: The extended half-life means steady-state concentrations accumulate with repeated dosing. Clinical trials used doses of 30-60 mcg/kg, with higher doses showing diminishing tolerability.

CJC-1295 without DAC (Modified GRF 1-29)

Half-Life: 30 minutes to 2 hours

Administration: Multiple daily injections (typically 1-3 times daily)

Mechanism: No albumin binding; relies solely on the four amino acid substitutions for enhanced stability compared to native GHRH (which has a <7-minute half-life)

Growth Hormone Pattern: Acute pulses mimicking physiological GH secretion. GH rises sharply within 15-30 minutes of injection, peaks around 1 hour, and returns to baseline within 2-3 hours.

IGF-1 Profile: Transient increases with each dose; cumulative effect with consistent daily dosing but less dramatic sustained elevation than the DAC version

Dosing Considerations: Requires multiple daily injections to maintain effect. Commonly administered 100-300 mcg per dose, often before sleep to augment the natural nocturnal GH pulse, and sometimes before exercise.

Clinical Implications of Pharmacokinetic Differences

The choice between CJC-1295 with and without DAC involves tradeoffs:

With DAC offers convenience (weekly dosing), sustained GH and IGF-1 elevation, and consistent effects. However, continuous stimulation may risk receptor downregulation, and less flexibility exists for dosing adjustments — once injected, the peptide remains active for days.

Without DAC preserves natural GH pulsatility, allows more precise control over timing and dose, and may reduce the risk of tolerance development. The tradeoff is inconvenience (multiple daily injections) and potentially less consistent IGF-1 elevation.

Neither version undergoes significant hepatic metabolism; both are cleared through renal filtration and proteolytic degradation. The primary difference lies in their bioavailability over time due to albumin binding.

Research Evidence

CJC-1295 underwent clinical evaluation through Phase II trials before development was discontinued. While the research base is limited compared to FDA-approved therapeutics, several well-designed studies provide insight into its effects.

Pivotal Phase I Studies

The primary evidence for CJC-1295's pharmacological activity comes from two randomized, placebo-controlled, double-blind, ascending-dose trials conducted in healthy adults aged 21-61 years over 28 and 49 days at two investigational sites.

Study Design: Participants received subcutaneous CJC-1295 at doses ranging from 30 to 60 mcg/kg or placebo. Blood samples were collected at regular intervals to measure growth hormone, IGF-1, and other parameters.

Growth Hormone Effects:

Single injection produced dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold
Elevated GH persisted for 6 or more days
Basal (trough) GH levels increased while pulsatile secretion was preserved
No change in pulse frequency or amplitude

IGF-1 Effects:

Single injection increased plasma IGF-1 by 1.5- to 3-fold
Elevation persisted for 9-11 days
Multiple doses maintained IGF-1 above baseline for up to 28 days
Dose-dependent response observed

Tolerability: The study concluded that subcutaneous administration of CJC-1295 was "safe and relatively well tolerated, particularly at doses of 30 or 60 mcg/kg." No serious adverse reactions were reported during the initial Phase I trials.

Half-Life: Estimated at 5.8-8.1 days, confirming the extended duration of action.

Preservation of GH Pulsatility

A subsequent study specifically examined whether continuous stimulation by CJC-1295 would suppress the pituitary's natural pulsatile GH secretion. The findings were reassuring: pulsatile GH secretion persisted during continuous stimulation by CJC-1295.

This contrasts with continuous exogenous growth hormone administration, which suppresses endogenous pulsatile secretion through negative feedback. CJC-1295's preservation of pulsatility suggests it amplifies rather than replaces natural GH secretion patterns.

Animal Studies: GHRH Knockout Mice

Research in GHRH knockout mice demonstrated that once-daily administration of CJC-1295 normalized growth in animals genetically unable to produce endogenous GHRH. This proof-of-concept study showed that CJC-1295 could functionally replace native GHRH when administered chronically.

Weight gain, body length, and other growth parameters in treated knockout mice approximated those of wild-type controls, suggesting effective GHRH receptor activation and downstream GH/IGF-1 axis function.

Protein Profile Changes

One study examined serum protein changes resulting from GH/IGF-1 axis activation by CJC-1295. The research identified alterations in serum protein profiles that reflected metabolic and anabolic effects of sustained GH elevation, including changes consistent with increased protein synthesis and altered lipid metabolism.

Limitations of the Research Base

Despite these promising findings, significant limitations exist:

Limited Human Data: Only Phase I and early Phase II trials were completed before development ceased

Healthy Subjects Only: Most data comes from young, healthy adults rather than patients with growth hormone deficiency or other target conditions

Short Duration: The longest trial was 49 days — insufficient to assess long-term safety or efficacy

Discontinuation After Death: A Phase II study in HIV-associated lipodystrophy was halted after one participant's death. The attending physician believed the most likely explanation was asymptomatic coronary artery disease with plaque rupture unrelated to CJC-1295, but development was terminated as a precaution.

No FDA Approval: CJC-1295 never completed the regulatory pathway to approval

No published research examines CJC-1295 in the contexts for which it's commonly used off-label: bodybuilding, anti-aging, athletic performance, or body composition. The evidence base consists entirely of early-phase pharmacokinetic and safety studies in healthy volunteers and proof-of-concept animal models.

CJC-1295 and Ipamorelin: The Popular Combination

One of the most common applications of CJC-1295 in clinical practice and research is its combination with ipamorelin, a selective growth hormone-releasing peptide (GHRP). This pairing has become nearly ubiquitous in peptide therapy protocols, but the rationale deserves examination.

Why Combine GHRH Analogs and GHRPs?

CJC-1295 and ipamorelin stimulate growth hormone release through distinct, complementary mechanisms:

CJC-1295 activates GHRH receptors on pituitary somatotrophs, signaling the cells to synthesize and secrete growth hormone through the cAMP/protein kinase A pathway.

Ipamorelin binds to ghrelin receptors (GHS-R1a), also located on somatotrophs, triggering GH release through a different intracellular signaling cascade involving phospholipase C and intracellular calcium mobilization.

When both pathways are activated simultaneously, they produce synergistic effects — growth hormone release exceeds what either compound produces individually. Research indicates the combination typically produces a 3- to 5-fold increase in growth hormone release over ipamorelin alone.

Pharmacokinetic Compatibility

The two peptides have complementary pharmacokinetic profiles:

Ipamorelin: Fast-acting with a ~2-hour half-life, producing acute GH pulses

CJC-1295 without DAC: 30-minute to 2-hour half-life, matching ipamorelin's timeframe for acute dosing

CJC-1295 with DAC: 6-8 day half-life, providing sustained baseline GH elevation while ipamorelin creates superimposed peaks

The combination of ipamorelin's rapid onset and CJC-1295 (particularly the DAC version) sustained effects creates both immediate and prolonged GH elevation — "instant response with long-lasting effects," as one clinical source describes it.

Claimed Synergistic Benefits

Advocates of combination therapy claim several advantages over either peptide alone:

Enhanced GH Release: The synergistic mechanism theoretically maximizes growth hormone output from existing pituitary capacity

Preservation of Pulsatility: Even when using CJC-1295 with DAC (which elevates baseline GH), ipamorelin adds acute pulses, potentially maintaining more physiological patterns than continuous elevation alone

Selectivity: Ipamorelin is notable among GHRPs for selective GH release without significantly increasing cortisol or prolactin — hormonal side effects common with older GHRPs like GHRP-2 or GHRP-6

Complementary Effects on Body Composition: Both peptides are claimed to support muscle growth, fat loss, and recovery, with combined effects potentially exceeding individual contributions

Typical Combination Protocols

Common dosing recommendations for combination therapy include:

CJC-1295 without DAC + Ipamorelin:

100-300 mcg of each peptide per dose
Administered together, typically before sleep and/or before exercise
Once or twice daily dosing

CJC-1295 with DAC + Ipamorelin:

CJC-1295 with DAC: 300-1000 mcg once weekly
Ipamorelin: 100-300 mcg once or twice daily
CJC-1295 maintains baseline elevation; ipamorelin adds pulsatile stimulation

Subcutaneous injection is the standard administration route, with evening dosing preferred to align with the body's natural nocturnal GH surge.

Evidence Limitations

Despite widespread use, direct clinical evidence for CJC-1295/ipamorelin combination therapy is limited. The synergistic mechanism is based on established GHRH and GHRP physiology rather than specific combination studies. No published trials have directly compared the combination to either peptide alone in humans, and no research examines long-term safety or efficacy of combined use.

The practice is primarily based on:

Mechanistic rationale (two complementary pathways)
Extrapolation from separate studies of each compound
Clinical experience and anecdotal reports

As with many aspects of peptide therapy, the popularity of CJC-1295/ipamorelin combinations in clinical practice has outpaced the formal evidence base.

CJC-1295 vs. Other GHRH Analogs

CJC-1295 belongs to a family of synthetic GHRH analogs developed to improve upon native GHRH's extremely short half-life. Comparing these analogs reveals important differences in pharmacology, regulatory status, and clinical applications.

CJC-1295 vs. Sermorelin

Sermorelin is the simplest GHRH analog — identical to native GHRH (1-29) without additional modifications. This fundamental difference has significant implications:

Half-Life:

Sermorelin: A few minutes to hours
CJC-1295 without DAC: 30 minutes to 2 hours
CJC-1295 with DAC: 6-8 days

Dosing:

Sermorelin requires daily injection, typically at bedtime
CJC-1295 without DAC: Daily or twice-daily
CJC-1295 with DAC: Weekly

Regulatory Status:

Sermorelin was previously FDA-approved as a diagnostic agent (Geref) for assessing growth hormone secretion, though the approved product is no longer manufactured
CJC-1295 has never received FDA approval

Clinical Use:

Sermorelin is often described as working more gently, mimicking natural hormone rhythms, and is recommended for beginners or gradual support
CJC-1295 (particularly with DAC) produces stronger, longer-lasting GH elevation and more noticeable results

Research Base:

Sermorelin has far more published research than CJC-1295
Some analyses suggest CJC-1295 has not performed as well as sermorelin in studies, with some trials discontinued due to lack of results (though this may also relate to the safety concerns that halted development)

The choice between sermorelin and CJC-1295 often depends on treatment goals: sermorelin for natural-pattern support and anti-aging, CJC-1295 for more pronounced effects on muscle mass, fat reduction, and recovery.

CJC-1295 vs. Tesamorelin

Tesamorelin is another modified GHRH analog, but with one critical distinction: FDA approval. Tesamorelin (brand name Egrifta) is approved specifically for reducing excess abdominal fat in HIV-infected patients with lipodystrophy.

Regulatory Status: Tesamorelin is FDA-approved; CJC-1295 is not

Clinical Application: Tesamorelin has a defined medical indication; CJC-1295 use is entirely off-label

Structure: Both are modified versions of GHRH (1-29), though with different modifications

Half-Life: Tesamorelin has a relatively short half-life (approximately 26 minutes in HIV patients, 38 minutes in healthy subjects), similar to CJC-1295 without DAC

The existence of FDA-approved tesamorelin for a similar mechanism raises questions about why CJC-1295 didn't complete development. The discontinuation following a participant death, even if unrelated to treatment, appears to have ended the commercial pathway.

CJC-1295 vs. MK-677 (Ibutamoren)

While MK-677 is often discussed alongside GHRH analogs in growth hormone optimization contexts, it operates through a fundamentally different mechanism:

Structure: MK-677 is not a peptide but a small-molecule ghrelin mimetic

Mechanism: Activates the ghrelin receptor (like ipamorelin) rather than the GHRH receptor

Administration: Oral (not injectable like CJC-1295)

Half-Life: Approximately 4-6 hours

Effects: Increases appetite significantly (through ghrelin pathway), unlike CJC-1295

MK-677 is sometimes used as an alternative to injectable peptides for those preferring oral administration, though its appetite-stimulating effects and different mechanism make it functionally distinct from GHRH analogs.

Combined Approach

Some protocols use CJC-1295 with sermorelin concurrently, combining CJC-1295's extended baseline elevation with sermorelin's natural pulsatile pattern. The intention is to blend steady background stimulation with sharper physiological pulses, though no published research validates this specific combination's superiority to either agent alone.

Safety Profile and Side Effects

The safety profile of CJC-1295 is incompletely characterized due to the limited duration of clinical trials and lack of post-marketing surveillance that would accompany an approved drug.

Common Side Effects

Clinical trials reported that CJC-1295 was "safe and relatively well tolerated" at doses of 30-60 mcg/kg, with no serious adverse reactions in initial Phase I studies. Common minor effects included:

Injection Site Reactions:

Pain, redness, or swelling at the injection site
These are typical of subcutaneous peptide injections and generally resolve within hours to days

Flushing:

Facial flushing or warmth
Reported in a small percentage of users
Related to vasodilatory effects from GH axis activation

Water Retention:

Mild, transitory fluid retention
Related to GH's effects on sodium retention and fluid balance

Other Minor Effects:

Headache (<1% of patients in some reports)
Dizziness (<1%)
Hyperactivity (<1%)
Light-headedness after administration

These effects are generally mild and transient, resolving without intervention.

Serious Adverse Events

Death During Clinical Trial: The most significant safety concern emerged when a Phase II study was halted after one participant's death. The attending physician believed the most likely cause was asymptomatic coronary artery disease with plaque rupture and occlusion, unrelated to CJC-1295 treatment. Nonetheless, research was terminated as a precautionary measure.

This incident, whether causally related or coincidental, ended CJC-1295's path to FDA approval. The fact that development ceased entirely rather than continuing with enhanced safety monitoring suggests either sponsor concerns about liability or insufficient commercial potential to justify continued investment.

Cardiovascular Effects: The FDA has warned about risks of increased heart rate and systemic vasodilatory reactions, including:

Flushing
Warmth
Transient hypotension (temporary low blood pressure)

These effects relate to growth hormone's cardiovascular actions and should be considered in individuals with existing heart conditions.

Metabolic Effects: Growth hormone influences glucose metabolism, and reports include:

Increased insulin resistance
Persistent hyperglycemia in some cases
Potential effects on blood glucose control

Individuals with diabetes or prediabetes may experience altered glucose regulation with CJC-1295 use, requiring monitoring and potential adjustment of glucose-lowering medications.

Cancer Concerns

Growth hormone secretagogues generally carry theoretical cancer risk due to GH and IGF-1's roles in cell proliferation. By virtue of inducing broad cell growth, these compounds may:

Increase cancer recurrence risk in survivors
Worsen prognosis in individuals with active cancer
Potentially promote tumor growth in undiagnosed malignancies

The relationship between GH/IGF-1 elevation and cancer is complex and context-dependent. Some epidemiological data links higher IGF-1 levels to increased prostate, breast, and colorectal cancer risk, while other research finds no clear association. The issue remains unresolved, but caution is warranted in individuals with cancer history or elevated baseline cancer risk.

Immunogenicity

As a modified protein, CJC-1295 has potential for immune reactions:

Antibody formation against the peptide
Potential allergic reactions
Reduced efficacy over time if neutralizing antibodies develop

The albumin-binding DAC modification introduces a reactive chemical group that could theoretically trigger immune responses, though systematic assessment of immunogenicity was not completed before development ended.

Hormonal Interactions

CJC-1295 may interact with:

Thyroid medications: GH can influence thyroid hormone conversion
Corticosteroids: May alter the balance of anabolic and catabolic signals
Insulin and diabetes medications: GH opposes insulin action, potentially requiring dose adjustments
Other growth hormone therapies: Additive effects with direct GH administration or other secretagogues

Long-Term Safety Unknown

The longest published trial was 49 days — far too short to assess chronic effects. Unanswered questions include:

Effects on pituitary function after months or years of use
Whether receptor downregulation or tachyphylaxis occurs
Long-term cardiovascular, metabolic, and cancer risks
Effects in pediatric, elderly, or special populations

The incomplete safety profile reflects CJC-1295's status as an unapproved, investigational compound. Users accept unknown long-term risks.

Legal and Regulatory Status

CJC-1295's regulatory status is complex and has changed significantly in recent years, particularly regarding compounding pharmacy access.

FDA Approval Status

CJC-1295 has never been approved by the FDA for any therapeutic indication. It remains an investigational compound without established safety or efficacy for human use. This means:

No approved medical uses exist
No quality standards or manufacturing requirements apply
No post-marketing surveillance occurs
All use is inherently off-label and experimental

Compounding Pharmacy Regulations

For years, compounding pharmacies provided access to CJC-1295 under Section 503A of the Federal Food, Drug, and Cosmetic Act, which allows compounding of drugs not commercially available if they meet certain criteria. Peptides could be compounded from bulk substances on the FDA's "Category 2" list — substances under evaluation for safety but not yet prohibited.

Major Regulatory Change (2024-2025): In September 2024, the FDA announced that five peptide bulk drug substances — including CJC-1295 and ipamorelin — were removed from the Category 2 list. After review by the Pharmacy Compounding Advisory Committee (PCAC), the FDA recommended against including these substances in the 503A Bulks Regulation.

Current Status: CJC-1295 is prohibited for compounding. The FDA's compliance status lists it as "Prohibited for Compounding," citing safety concerns and regulatory risks. Compounding pharmacies cannot legally compound CJC-1295 after its removal from Category 2 and the FDA's recommendation against 503A inclusion.

This creates significant uncertainty:

CJC-1295 remains in "regulatory limbo" — removed from Category 2 but not added to Category 1 (substances eligible for compounding)
Compounding remains suspended while evaluation continues
No clear pathway exists for legal access through compounding pharmacies
Some sources suggest legal battles are ongoing regarding the FDA's authority to restrict compounding of these substances

Research and Clinical Use

Research Contexts: CJC-1295 may be used in controlled research settings under appropriate institutional review board (IRB) approval and with proper informed consent. Research peptide suppliers typically market products "for research purposes only, not for human consumption," though enforcement of this restriction varies.

Off-Label Clinical Use: Prior to the 2024 compounding restrictions, some physicians prescribed CJC-1295 off-label through compounding pharmacies for indications such as:

Growth hormone deficiency
Age-related GH decline
Body composition optimization
Athletic performance and recovery

This practice has been curtailed by the compounding prohibition, though it's unclear what proportion of prescribers have discontinued use or sought alternative sources.

Gray Market: With reduced legitimate access, a gray market exists for research peptides including CJC-1295, often sourced internationally or from suppliers operating in legal ambiguity. These products lack quality assurance, sterility verification, or accurate dosing — significant safety concerns.

International Status

Regulatory status varies by country:

Most jurisdictions treat CJC-1295 as an unapproved drug, similar to U.S. policy
Some countries have less restrictive peptide regulations
Importation for personal use occupies legal gray areas in many places

Contrast with Approved GHRH Analogs

The existence of FDA-approved tesamorelin for HIV-associated lipodystrophy demonstrates that GHRH analogs can achieve regulatory approval with sufficient safety and efficacy data. CJC-1295's failure to reach approval despite mechanistic similarities to tesamorelin highlights the importance of completing clinical development programs.

Bottom Line on Legality

As of 2026, CJC-1295 occupies a restrictive regulatory position:

Not FDA-approved for any use
Prohibited for pharmacy compounding
Available only through research suppliers (with explicit "not for human use" restrictions) or gray-market sources
All human use is experimental and carries legal and safety risks

Anyone considering CJC-1295 should understand they're using an unapproved, inadequately studied compound without the safeguards that accompany approved medications.

Frequently Asked Questions

What's the difference between CJC-1295 with DAC and without DAC?

The Drug Affinity Complex (DAC) is a chemical modification that enables CJC-1295 to bind covalently to serum albumin, dramatically extending its half-life from 30 minutes to 6-8 days. CJC-1295 with DAC requires only weekly injections and provides sustained baseline GH elevation. CJC-1295 without DAC — more accurately called Modified GRF (1-29) — requires daily or twice-daily injections but preserves more natural pulsatile GH patterns. The version without DAC is often preferred for maintaining physiological hormone rhythms, while the DAC version offers convenience and consistent effects.

Is CJC-1295 the same as sermorelin?

No. While both are GHRH analogs, sermorelin is identical to the first 29 amino acids of natural GHRH without modifications. CJC-1295 (Modified GRF 1-29) contains four strategic amino acid substitutions that dramatically improve stability and half-life. Sermorelin has a half-life of only minutes, requiring daily injection, while CJC-1295 without DAC lasts 30 minutes to 2 hours, and with DAC lasts up to 8 days. Sermorelin has more clinical research and was previously FDA-approved as a diagnostic agent, while CJC-1295 never achieved approval.

How long does CJC-1295 stay in your system?

This depends on the version. CJC-1295 with DAC has a half-life of 5.8-8.1 days, meaning detectable levels persist for approximately two weeks or longer after a single injection. IGF-1 elevations can last 9-11 days after a single dose and up to 28 days with repeated dosing. CJC-1295 without DAC (Modified GRF 1-29) has a much shorter half-life of 30 minutes to 2 hours, clearing the system within several hours of injection, though effects on GH release persist for 2-3 hours.

Can you take CJC-1295 and ipamorelin together?

Yes, and this is actually one of the most common peptide combinations in clinical practice. CJC-1295 and ipamorelin work through complementary pathways — CJC-1295 activates GHRH receptors while ipamorelin activates ghrelin receptors — producing synergistic effects on growth hormone release. Studies suggest the combination produces 3- to 5-fold greater GH release than ipamorelin alone. They can be mixed in the same syringe and injected together, typically at doses of 100-300 mcg each, once or twice daily (for CJC-1295 without DAC) or with CJC-1295 with DAC weekly plus ipamorelin daily.

What are the side effects of CJC-1295?

Clinical trials reported CJC-1295 was generally well tolerated, with common minor side effects including injection site reactions (pain, redness, swelling), facial flushing, mild water retention, and occasional headache or dizziness. More serious concerns include potential cardiovascular effects (increased heart rate, transient low blood pressure), metabolic changes (insulin resistance, elevated blood glucose), and theoretical cancer risk due to growth hormone's cell proliferation effects. One participant death during a Phase II trial led to study termination, though the death was believed unrelated to treatment. Long-term safety data is lacking since development was discontinued.

Is CJC-1295 legal?

CJC-1295 has never been FDA-approved for human use. As of 2024, the FDA removed it from the Category 2 list and prohibited compounding pharmacies from preparing it, citing safety concerns. This means legitimate pharmacy access has been eliminated. CJC-1295 remains available from research peptide suppliers marketed "for research purposes only, not for human consumption," though enforcement of this restriction is inconsistent. All human use is technically experimental and off-label. Anyone using CJC-1295 should understand they're using an unapproved substance without the quality controls and safety monitoring of approved medications.

Does CJC-1295 need to be refrigerated?

Yes. Peptides are sensitive to heat and light degradation. Lyophilized (freeze-dried) CJC-1295 powder should be stored refrigerated at 2-8°C (36-46°F) or frozen for longer-term storage. Once reconstituted with bacteriostatic water, it must be refrigerated and used within the timeframe specified by the supplier — typically 30 days for most peptides. Never freeze reconstituted peptides, as ice crystal formation can damage the peptide structure. Protect from light by storing in opaque containers or wrapping vials in foil.

How much does CJC-1295 increase growth hormone?

Clinical data shows dose-dependent effects. After a single injection of CJC-1295 with DAC, mean plasma growth hormone concentrations increased by 2- to 10-fold for six or more days, with IGF-1 increasing 1.5- to 3-fold for 9-11 days. The specific increase depends on dose (30-60 mcg/kg in studies), baseline GH status, and individual responsiveness. Importantly, CJC-1295 appears to elevate basal (trough) GH levels rather than increasing pulse amplitude, meaning it raises the baseline from which natural pulses occur rather than creating larger peaks.

The Bottom Line

CJC-1295 represents an elegant solution to a pharmacological problem — native GHRH's seven-minute half-life made it impractical for therapeutic use. Through strategic amino acid substitutions and, optionally, albumin-binding modification, researchers created a peptide that stimulates growth hormone release for hours or days instead of minutes.

The clinical data, though limited, demonstrates clear pharmacological activity. Single injections of CJC-1295 with DAC produce sustained 2- to 10-fold increases in growth hormone and 1.5- to 3-fold increases in IGF-1 lasting over a week. The peptide preserves natural GH pulsatility while elevating baseline levels, avoiding some concerns associated with continuous exogenous GH administration. Early trials found it reasonably well tolerated at moderate doses.

Yet CJC-1295 exists in regulatory and evidential limbo. Clinical development ended abruptly following a participant death during Phase II trials, leaving critical questions unanswered: Does it work for the conditions people use it for — body composition, athletic performance, anti-aging? What happens with months or years of continuous use? Does tolerance develop? What are the true long-term cardiovascular, metabolic, and cancer risks?

The FDA's 2024 decision to prohibit compounding reflects these unresolved safety concerns. With no approved indications and restricted legal access, CJC-1295 occupies an uncomfortable space — mechanistically sound, pharmacologically active, but inadequately studied and unavailable through legitimate channels.

For researchers and clinicians, CJC-1295 remains an interesting proof-of-concept in peptide modification strategies. The existence of FDA-approved tesamorelin demonstrates that GHRH analogs can achieve approval with sufficient data, suggesting CJC-1295's fate reflects incomplete development rather than fundamental unsuitability.

For individuals considering use, the calculus is more difficult. Anecdotal reports describe benefits for muscle growth, fat loss, and recovery, but these exist without controlled trial support. The safety profile appears reasonable in short-term use but remains incompletely characterized for chronic administration. Legal access is restricted, raising quality and sterility concerns with alternative sources.

CJC-1295 is neither miracle drug nor dangerous poison — it's an investigational compound with demonstrated pharmacological activity, plausible mechanisms, incomplete safety data, and uncertain regulatory future. Anyone using it should understand they're participating in an uncontrolled experiment, accepting unknown risks for unproven benefits.

The most scientifically honest statement about CJC-1295 is this: we know it increases growth hormone and IGF-1 in ways that last longer than previous GHRH analogs. We don't know if those increases translate to meaningful clinical benefits, whether they're safe long-term, or who might be most helped or harmed by its use. Until those questions are answered through rigorous research, CJC-1295 remains a compound defined more by its unrealized potential than by proven therapeutic value.

This article is for educational purposes only. PeptideJournal.org does not sell peptides, provide medical advice, or recommend the use of any unapproved substances. CJC-1295 is not FDA-approved and is prohibited for compounding under current regulations. All use is experimental and should only occur under qualified medical supervision with appropriate informed consent and monitoring. Always consult a qualified healthcare provider before making decisions about your health.

References

Teichman SL, Neale A, Lawrence B, et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805.
Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797.
Jetton AE, Chaudhary A, Hewitt BL, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006;291(6):E1290-E1294.
Liang R, Liu S, Zhao Y, et al. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res. 2009;19(6):471-477.
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Sadick N, Makino E, Weiss R. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3179-3186.
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FDA Pharmacy Compounding Advisory Committee: CJC-1295. FDA. 2024.
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What is CJC1295 without DAC? BOC Sciences. Accessed February 15, 2026.
CJC-1295 DAC: Structure, Mechanism, and Research Findings. Biotech Peptides. January 19, 2026.

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