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CJC-1295 with DAC: Extended-Release Research

CJC-1295 with DAC represents one of the more sophisticated approaches to growth hormone modulation through peptide technology.

CJC-1295 with DAC represents one of the more sophisticated approaches to growth hormone modulation through peptide technology. The addition of a Drug Affinity Complex transforms a short-acting peptide into a long-lasting analog with an 8-day half-life, creating a fundamentally different physiological effect compared to its non-DAC counterpart. Originally developed by ConjuChem Biotechnologies for treating lipodystrophy and growth hormone deficiency, this peptide reached Phase II clinical trials before development halted following a trial participant's death—though the attending physician concluded the cardiac event was unrelated to treatment. What makes CJC-1295 with DAC noteworthy is its mechanism: a maleimidopropionic acid linker enables covalent binding to serum albumin, creating sustained elevation of both growth hormone and IGF-1 levels that persist for over a week from a single injection.

The distinction between CJC-1295 with DAC and the widely-used CJC-1295 without DAC (also called modified GRF 1-29) goes beyond convenience. The DAC version creates continuous GHRH stimulation, elevating baseline GH levels between pulses rather than generating discrete pulses like the short-acting version or natural Sermorelin. This "GH bleed" pattern produces different metabolic effects and requires different dosing protocols—typically twice weekly rather than multiple daily injections. Research demonstrates dose-dependent increases in mean plasma GH by 2- to 10-fold for six days or more, with IGF-1 elevations lasting 9-11 days after a single administration.

Understanding CJC-1295 with DAC requires distinguishing marketing claims from clinical evidence, recognizing its current regulatory status, and appreciating why its albumin-binding technology represents both an achievement in peptide pharmacology and a cautionary tale about drug development complexity.

Table of Contents

Quick Facts: CJC-1295 with DAC

PropertyDetail
Chemical NameNɛ30-maleimidopropionyl-[D-Ala2, Gln8, Ala15, Leu27]-Sermorelin-Lys30
ClassificationGrowth hormone-releasing hormone (GHRH) analog with Drug Affinity Complex
MechanismCovalent binding to serum albumin via maleimidopropionic acid linker, enabling sustained GHRH receptor activation
Half-Life5.8-8.1 days (approximately 6-8 days)
DeveloperConjuChem Biotechnologies (Canada)
Clinical StatusPhase II trials discontinued; not FDA-approved
Typical Dosing300-1000 mcg subcutaneously twice weekly
GH Elevation2- to 10-fold increase lasting 6+ days
IGF-1 Elevation1.5- to 3-fold increase lasting 9-11 days
Regulatory StatusProhibited for compounding; removed from FDA Category 2 list

What Is CJC-1295 with DAC?

CJC-1295 with DAC is a synthetic analog of growth hormone-releasing hormone (GHRH) designed to stimulate the pituitary gland's production of growth hormone over an extended period. The peptide consists of 30 amino acids with four strategic substitutions that improve resistance to enzymatic degradation.

The Drug Affinity Complex (DAC) Technology

The defining feature of CJC-1295 with DAC is the addition of a reactive chemical group called maleimidopropionic acid (MPA) attached to a lysine residue at the peptide's C-terminus. This MPA group functions as the Drug Affinity Complex, enabling the peptide to form a covalent bond with the free thiol group on cysteine-34 of serum albumin once injected into the body.

Albumin is the most abundant protein in blood plasma, with a half-life of approximately 19-21 days. By binding to albumin, CJC-1295 essentially hitchhikes on this long-lived carrier protein, dramatically extending its own half-life from minutes to days. The peptide remains biologically active while albumin-bound, continuously stimulating GHRH receptors throughout its extended circulation time.

This bioconjugation approach represents a sophisticated form of peptide modification. Rather than requiring chemical attachment to albumin in a laboratory before administration, CJC-1295 with DAC performs this conjugation in vivo—the reactive maleimido group spontaneously binds to albumin after subcutaneous injection. The result is a self-assembling, long-acting formulation from a relatively small peptide.

Development History

ConjuChem Biotechnologies developed CJC-1295 with DAC in the mid-2000s as part of their platform for creating albumin-conjugated therapeutics. The company pursued clinical development for two primary indications: HIV-associated lipodystrophy (abnormal fat distribution) and growth hormone deficiency.

A 12-week Phase II clinical trial examined CJC-1295 with DAC in 192 patients with HIV-related visceral obesity. The study aimed to determine whether sustained GH elevation could reduce visceral fat accumulation, a significant problem for patients on antiretroviral therapy. However, one participant died of acute myocardial infarction approximately two hours after receiving the 11th weekly dose. Though the attending physician concluded the death resulted from pre-existing asymptomatic coronary artery disease unrelated to the study drug, ConjuChem halted the trial.

The company did not resume development, and CJC-1295 with DAC never reached market approval. Despite this, the peptide gained popularity in research communities and underground enhancement circles, largely due to the convenience of weekly dosing compared to multiple daily injections required by other GHRH analogs.

Distinguishing CJC-1295 With vs. Without DAC

A significant source of confusion surrounds CJC-1295 nomenclature. The term "CJC-1295" technically refers to the complete molecule including the DAC modification. However, a related peptide called modified GRF 1-29—which is identical to CJC-1295's first 29 amino acids but lacks the DAC-bearing lysine residue—is commonly marketed as "CJC-1295 without DAC" or "CJC-1295 no DAC."

These are functionally different compounds with distinct pharmacokinetics and physiological effects. Modified GRF 1-29 has a half-life of approximately 30 minutes and must be dosed multiple times daily to maintain effect. True CJC-1295 with DAC requires dosing only once or twice weekly due to its 6-8 day half-life. The naming convention creates marketplace confusion, as "CJC-1295" may refer to either version depending on vendor and context.

How CJC-1295 with DAC Works

CJC-1295 with DAC functions through activation of the growth hormone-releasing hormone (GHRH) receptor on somatotroph cells in the anterior pituitary gland. Understanding its mechanism requires examining both the GHRH system's normal physiology and how the DAC modification alters temporal dynamics.

The GHRH-GH Axis

Growth hormone secretion operates under dual control from the hypothalamus. GHRH, produced by neurons in the arcuate nucleus, stimulates GH release. Somatostatin, produced by periventricular neurons, inhibits it. These two signals oscillate throughout the day, creating pulsatile GH secretion—discrete bursts occurring primarily during deep sleep and after meals, with low levels between pulses.

When GHRH binds to its receptor on pituitary somatotrophs, it activates adenylyl cyclase, increasing intracellular cAMP levels. This triggers calcium influx and stimulates transcription of the GH gene, resulting in both immediate GH release from storage vesicles and increased GH synthesis for future secretion. The released GH then stimulates insulin-like growth factor 1 (IGF-1) production primarily in the liver, though many tissues produce IGF-1 locally in response to GH.

Natural GHRH has a half-life measured in minutes due to rapid enzymatic cleavage by dipeptidyl peptidase-4 (DPP-4) and other proteases. This short half-life allows for the pulsatile pattern—GHRH rises briefly, stimulates a GH pulse, then quickly disappears as somatostatin takes over to suppress further secretion until the next cycle.

CJC-1295 with DAC's Modified Action

CJC-1295 with DAC incorporates four amino acid substitutions (D-Ala2, Gln8, Ala15, Leu27) that confer resistance to enzymatic degradation. However, even with these modifications, the peptide's half-life would only extend to hours without the DAC component.

The maleimidopropionic acid linker changes everything. After subcutaneous injection, CJC-1295 with DAC diffuses into the bloodstream where the reactive maleimido group forms a covalent thioether bond with cysteine-34 on serum albumin. This reaction occurs spontaneously—no enzymatic catalyst required—and is essentially irreversible under physiological conditions.

Once albumin-bound, CJC-1295 circulates with an effective half-life matching that of albumin itself: approximately 6-8 days. The peptide remains biologically active while conjugated, continuously engaging GHRH receptors on pituitary somatotrophs. This creates fundamentally different stimulation dynamics compared to native GHRH or short-acting analogs.

Continuous Stimulation with Preserved Pulsatility

A critical finding from CJC-1295 research challenges assumptions about GHRH analog effects. One might expect that continuous GHRH receptor activation would override the body's natural pulsatile GH secretion pattern, creating steady-state GH levels. However, research by Ionescu and Frohman published in the Journal of Clinical Endocrinology & Metabolism demonstrated that GH pulsatility persists during continuous CJC-1295 stimulation.

In their study, the frequency and magnitude of GH secretory pulses remained unchanged after CJC-1295 administration. What changed dramatically was the baseline—the trough GH level between pulses increased 7.5-fold. This pattern suggests that even with continuous GHRH receptor engagement, the somatostatin system retains control over pulse timing. CJC-1295 raises the baseline around which normal pulses occur rather than eliminating the pulsatile pattern entirely.

This preservation of pulsatility may have physiological significance. Some research suggests pulsatile GH patterns produce different tissue effects than continuous elevation, though the clinical implications remain debated. The elevated baseline appears critical for driving sustained IGF-1 production—mean GH levels increased 46% in the Ionescu study, with corresponding IGF-1 increases of 45%.

Comparison to Growth Hormone Secretagogues

It's worth distinguishing CJC-1295's mechanism from growth hormone secretagogues (GHS) like Ipamorelin, GHRP-2, and GHRP-6. These compounds work through the ghrelin receptor (growth hormone secretagogue receptor, GHS-R), a distinct receptor system that synergizes with GHRH.

Ghrelin and GHS agonists stimulate GH release through multiple pathways: direct action on pituitary GHS receptors, stimulation of hypothalamic GHRH neurons, and inhibition of somatostatin release. The combination of a GHRH analog like CJC-1295 with a GHS creates additive or synergistic effects—activating both pathways simultaneously produces larger GH pulses than either alone.

This explains the popularity of CJC-1295 + Ipamorelin combinations. The short-acting modified GRF 1-29 (CJC-1295 without DAC) paired with Ipamorelin creates pronounced GH pulses that mimic supraphysiological versions of the body's natural secretion pattern. CJC-1295 with DAC, conversely, is less commonly combined with GHS because the continuous GHRH stimulation already produces sustained GH elevation—adding a GHS might amplify pulses but doesn't fundamentally change the long-duration profile.

CJC-1295 with DAC vs. Without DAC

The distinction between CJC-1295 with and without DAC extends beyond pharmacokinetics to encompass dosing, physiological patterns, practical considerations, and potentially different therapeutic applications.

Structural and Pharmacokinetic Differences

CJC-1295 with DAC (true CJC-1295):

  • 30 amino acids with maleimidopropionic acid linker at C-terminus
  • Forms covalent bond with serum albumin at cysteine-34
  • Half-life: 5.8-8.1 days
  • Dosing frequency: Once or twice weekly
  • Creates sustained GHRH receptor activation

CJC-1295 without DAC (modified GRF 1-29):

  • 29 amino acids, identical sequence to first 29 residues of CJC-1295 with DAC
  • No albumin-binding modification
  • Half-life: Approximately 30 minutes
  • Dosing frequency: 1-3 times daily
  • Creates discrete GHRH pulses

Modified GRF 1-29 is structurally identical to the GHRH-active portion of CJC-1295 with DAC, minus the DAC-bearing lysine. Both share the four amino acid substitutions that confer DPP-4 resistance, extending the half-life from the 2-3 minutes of natural GHRH to approximately 30 minutes. However, without albumin binding, modified GRF 1-29 remains a short-acting peptide.

Pattern of GH Release

The pharmacokinetic difference produces distinct GH secretion patterns:

With DAC: Creates elevated baseline GH levels that persist for days, with normal pulsatile secretion superimposed on this elevated baseline. Trough GH levels (between pulses) increase by 7.5-fold according to research, while maintaining normal pulse frequency and amplitude. This produces continuous GH/IGF-1 axis activation.

Without DAC: Generates discrete GH pulses that mimic natural secretion timing. When dosed before sleep or meals—times when endogenous GH pulses naturally occur—modified GRF 1-29 amplifies these physiological pulses. Between doses, GH levels return to baseline. This maintains the pulsatile pattern more closely aligned with normal physiology.

The clinical significance of this difference remains uncertain. Some researchers hypothesize that pulsatile GH patterns produce different receptor signaling than continuous elevation, potentially affecting downstream effects on lipolysis, protein synthesis, or glucose metabolism. However, definitive evidence demonstrating superior outcomes with either pattern in humans is limited.

Dosing Protocols

CJC-1295 with DAC:

  • Typical dose: 300-1000 mcg per injection
  • Frequency: Twice weekly, spaced 3-4 days apart
  • Timing: Can be administered at any time; timing less critical due to sustained effect
  • Titration: Often started at 300 mcg, increased by 250 mcg every 2 weeks based on tolerance

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

  • Typical dose: 100-300 mcg per injection
  • Frequency: 1-3 times daily
  • Timing: Usually before bed and/or before meals to align with natural GH pulses
  • Often combined with Ipamorelin or another GHS for synergistic effect

The convenience factor weighs heavily in practical application. Two injections weekly versus 7-21 injections weekly represents a significant difference in adherence burden. However, the short-acting version offers more control—effects wear off within hours if side effects occur, whereas CJC-1295 with DAC effects persist for over a week regardless of tolerance.

Practical Considerations

Storage and reconstitution: Both peptides typically require refrigerated storage after reconstitution with bacteriostatic water. CJC-1295 with DAC is generally considered more stable, likely due to the albumin binding providing additional protection from degradation once administered.

Cost: CJC-1295 with DAC typically costs more per dose than modified GRF 1-29, but the less frequent dosing may result in similar or lower overall cost depending on dosing protocols.

Combination protocols: Modified GRF 1-29 is almost universally combined with a growth hormone secretagogue like Ipamorelin to maximize GH pulse amplitude. The synergy between GHRH analogs and GHS is well-established—concurrent administration produces GH release approximately twice that of either alone. CJC-1295 with DAC is less commonly combined with GHS because the continuous stimulation already produces sustained elevation, though some protocols do pair them for amplified pulses.

Which Version for What Purpose?

The choice between versions depends on goals, tolerance for injection frequency, and philosophy about mimicking natural physiology:

CJC-1295 with DAC may be preferred when:

  • Convenience and adherence are priorities
  • Sustained IGF-1 elevation is the primary goal
  • Twice-weekly administration is acceptable
  • Continuous GH axis activation is desired

Modified GRF 1-29 may be preferred when:

  • Maintaining pulsatile patterns closer to natural physiology is valued
  • Flexibility to discontinue quickly if issues arise is important
  • Combination with a GHS for synergistic pulses is planned
  • More frequent dosing is acceptable

Neither version has FDA approval for any indication. Both exist in a regulatory gray area, discussed further in the Legal and Regulatory Status section.

Research Evidence

Clinical and preclinical research on CJC-1295 with DAC remains limited compared to FDA-approved therapeutics, but several studies provide insight into its effects on the GH/IGF-1 axis, pharmacokinetics, and physiological outcomes.

Healthy Adult Studies

The most comprehensive human data comes from two randomized, placebo-controlled, double-blind trials in healthy adults published by Teichman et al. in the Journal of Clinical Endocrinology & Metabolism (2006). These Phase I/II studies examined ascending doses of CJC-1295 over 28-49 days in subjects aged 21-61 years.

Key findings:

  • Single subcutaneous injections produced dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 days or more
  • Mean plasma IGF-1 levels increased 1.5- to 3-fold for 9-11 days after a single dose
  • Estimated half-life: 5.8-8.1 days
  • After multiple doses, mean IGF-1 levels remained above baseline for up to 28 days
  • No serious adverse reactions were reported in these trials

The dose-response relationship was clear: higher doses produced greater GH and IGF-1 elevations. However, even at lower doses, the duration of effect was substantially prolonged compared to natural GHRH or short-acting analogs.

These studies established proof of concept for albumin-conjugation technology extending peptide half-life and demonstrated sustained activation of the GH/IGF-1 axis in humans.

GH Pulsatility Study

A follow-up study by Ionescu and Frohman (2006) specifically examined whether continuous GHRH stimulation by CJC-1295 would override normal pulsatile GH secretion. Using 20-minute blood sampling over 12-hour overnight periods in healthy men aged 20-40, they assessed GH pulsatility before and one week after CJC-1295 injection.

Key findings:

  • GH pulse frequency and amplitude were preserved—the normal pulsatile pattern continued
  • Basal (trough) GH levels increased 7.5-fold between pulses
  • Overall mean GH levels increased 46%
  • IGF-1 levels increased 45%

This study demonstrated that the somatostatin system retains control over GH pulse timing even during continuous GHRH receptor activation. CJC-1295 elevates the baseline around which normal pulses occur rather than creating steady-state GH levels.

Animal Studies

Research in GHRH knockout mice (Alba et al., 2006) examined whether once-daily CJC-1295 could normalize growth in animals completely lacking endogenous GHRH. Published in the American Journal of Physiology-Endocrinology and Metabolism, this study showed that CJC-1295 restored normal growth rates and normalized body composition in knockout mice that otherwise exhibited severe growth impairment.

Key findings:

  • Once-daily CJC-1295 normalized weight gain in GHRH knockout mice
  • Relative lean mass and subcutaneous fat mass normalized in treated groups
  • Effects were comparable to mice receiving multiple daily GHRH injections

This study established that long-acting GHRH analogs could replace endogenous GHRH function and supported the concept that sustained GHRH receptor activation produces physiologically relevant effects on growth and body composition.

Protein Profile Changes

A 2009 study by Thorner et al. examined how CJC-1295-induced activation of the GH/IGF-1 axis affected serum protein profiles in normal adults. Using proteomics analysis, they identified changes in multiple proteins involved in metabolism, inflammation, and coagulation.

Some of the identified protein changes correlated with decreases in fat mass and increases in lean mass, consistent with known GH effects on body composition. However, this study highlighted that GH axis activation produces widespread metabolic effects beyond simple IGF-1 elevation—an important consideration for understanding both therapeutic potential and safety.

Limitations of Existing Research

Several significant gaps limit conclusions about CJC-1295 with DAC:

  1. No completed efficacy trials: The lipodystrophy trial was halted before completion. No published trials examine body composition, muscle mass, fat loss, or other outcomes claimed in enhancement contexts.

  2. Healthy subject data only: Published human studies involved healthy adults, not populations with GH deficiency, aging-related decline, or performance enhancement goals.

  3. Short duration: Most studies lasted weeks to months. Long-term safety and efficacy data over years are absent.

  4. No comparative trials: No published head-to-head trials compare CJC-1295 with DAC to recombinant GH, other GHRH analogs like Tesamorelin, or placebo for specific clinical outcomes.

  5. Publication bias: Only studies showing successful GH/IGF-1 elevation were published. Unpublished negative results or failed development programs may exist.

The evidence demonstrates that CJC-1295 with DAC effectively activates the GH/IGF-1 axis with sustained effect, but proof of clinically meaningful benefits for specific indications remains limited.

Research vs. Marketing Claims

A significant gap exists between research evidence and marketing claims in enhancement contexts. Common claims include:

  • "Promotes muscle growth": While GH elevation theoretically supports anabolism, no published trials demonstrate muscle mass increases with CJC-1295 specifically. Studies showing GH effects on muscle typically used recombinant GH or examined GH-deficient populations, not GHRH analog effects in normal individuals.

  • "Burns fat": GH has lipolytic effects, but the halted lipodystrophy trial provides no published data on whether CJC-1295 actually reduced fat mass in that population.

  • "Improves recovery": GH supports tissue repair, but specific evidence for CJC-1295 improving recovery from injury or exercise is lacking.

  • "Anti-aging effects": GH declines with age, but trials showing benefits of GH replacement in aging have produced mixed results, and whether GHRH analog stimulation produces similar effects is unknown.

  • "Improves sleep": GH secretion occurs during deep sleep, but whether elevating GH with CJC-1295 improves sleep quality lacks direct evidence.

These claims extrapolate from general GH physiology rather than specific CJC-1295 research. The peptide clearly elevates GH and IGF-1, but translating that elevation into meaningful clinical outcomes requires evidence that does not yet exist in the published literature.

Dosing and Administration

Information about CJC-1295 with DAC dosing comes primarily from research protocols, compounding pharmacy guidelines, and anecdotal reports from online communities rather than FDA-approved prescribing information (which doesn't exist, as the compound is not approved).

Typical Research Dosing

In the Teichman et al. studies, single subcutaneous doses ranged from 30 to 120 mcg/kg. For a 70 kg (154 lb) person, this translates to approximately 2,100-8,400 mcg per dose—substantially higher than doses commonly discussed in enhancement contexts.

Weekly dosing of 60 mcg/kg (approximately 4,200 mcg for a 70 kg person) was examined in the lipodystrophy trial before it was halted. Multiple doses maintained elevated IGF-1 levels for up to 28 days after the last injection.

Compounding Pharmacy Protocols

Before CJC-1295's removal from the FDA's Category 2 substance list, compounding pharmacies typically suggested:

  • Starting dose: 300-500 mcg twice weekly
  • Maintenance dose: 500-1000 mcg twice weekly
  • Injection timing: Spaced 3-4 days apart (e.g., Monday and Thursday)
  • Titration: Gradual increases of 200-250 mcg every 2 weeks based on tolerance and IGF-1 response

These doses are significantly lower than research protocols but were thought to balance efficacy with safety and cost considerations.

Administration Technique

CJC-1295 with DAC is administered via subcutaneous injection—the same technique used for insulin or other peptide therapeutics like Semaglutide.

Reconstitution: The lyophilized (freeze-dried) peptide is typically reconstituted with bacteriostatic water. Common concentrations range from 2 mg/mL to 5 mg/mL depending on vial size.

Injection sites: Common sites include:

  • Abdomen (at least 2 inches from navel)
  • Anterior thigh
  • Upper arm (deltoid area)

Site rotation: Rotating injection sites systematically reduces the risk of lipohypertrophy (fatty lumps at injection sites) and improves absorption consistency.

Technique:

  1. Clean injection site with alcohol swab
  2. Pinch skin to create a fold
  3. Insert needle at 45-90 degree angle
  4. Inject slowly
  5. Withdraw needle and apply gentle pressure (don't rub)

Timing Considerations

Unlike modified GRF 1-29, which is typically dosed before sleep or meals to align with natural GH pulses, CJC-1295 with DAC timing is less critical due to its sustained effect. Injections can occur at any time of day, though consistency helps with adherence.

Some protocols suggest evening administration on the theory that GH elevation during sleep may be particularly beneficial, but evidence supporting optimal timing is lacking.

Monitoring

Because CJC-1295 with DAC elevates IGF-1 levels for extended periods, monitoring via blood tests has been suggested in medical contexts:

  • IGF-1 levels: Baseline and periodic testing (every 1-3 months) to assess response and ensure levels remain in desired ranges
  • Glucose/HbA1c: GH opposes insulin action; monitoring for impaired glucose tolerance in susceptible individuals
  • Thyroid function: Some evidence suggests long-term GH elevation may affect thyroid function

Interpretation of IGF-1 levels requires context—age-adjusted reference ranges are essential, as normal IGF-1 declines with age. The goal is typically to achieve IGF-1 levels in the upper-normal range for age, not supraphysiological levels.

Duration of Use

No established guidelines exist for duration of CJC-1295 with DAC use. Enhancement protocols mentioned in forums typically describe cycles of 3-6 months followed by breaks, though the rationale for specific durations is unclear. Some concerns about continuous GH axis activation include:

  • Receptor downregulation: Chronic stimulation might reduce GHRH receptor sensitivity, though evidence for this with CJC-1295 is limited
  • Glucose tolerance: Prolonged GH elevation can impair insulin sensitivity
  • Unknown long-term effects: Safety beyond several months is unstudied

Medical supervision, if used, would likely involve periodic assessment to guide duration decisions.

Drug Interactions

CH-1295 with DAC's primary interaction risk involves other substances affecting GH secretion or glucose metabolism:

  • Somatostatin analogs (octreotide, lanreotide): Would directly oppose CJC-1295's effects
  • Glucocorticoids: Reduce GH secretion and tissue sensitivity
  • Insulin or antidiabetic medications: GH's anti-insulin effects could affect glucose control
  • Thyroid hormones: Interactions between GH and thyroid axes are complex

The peptide's lack of extensive drug interaction studies means additional interactions may exist.

Safety and Side Effects

Safety data for CJC-1295 with DAC comes from limited clinical trials in healthy adults, the halted lipodystrophy trial, and anecdotal reports from non-medical use. No long-term safety studies exist.

Clinical Trial Safety Data

In the Teichman et al. healthy adult studies, subcutaneous CJC-1295 was described as "safe and relatively well tolerated." No serious adverse events were reported in these short-duration trials. The most common side effects were:

  • Injection site reactions (erythema, mild swelling, tenderness)
  • Flushing
  • Headache
  • Fatigue
  • Nausea (occasional)

These effects were generally mild and transient. However, the studies involved carefully screened healthy subjects monitored in clinical settings—a very different population and context than unmonitored use.

Cardiovascular Concerns: The Lipodystrophy Trial Death

The most significant safety signal comes from the halted Phase II lipodystrophy trial. One of 192 enrolled participants died of acute myocardial infarction approximately two hours after receiving the 11th weekly dose of 2 mg (2000 mcg) CJC-1295.

The participant complained of chest discomfort, and an ECG confirmed acute MI. Death occurred approximately one hour after the ECG. The attending physician concluded that the most likely explanation was pre-existing asymptomatic coronary artery disease with spontaneous plaque rupture and occlusion, unrelated to CJC-1295 treatment.

However, this event led ConjuChem to halt the trial and discontinue development. Whether CJC-1295 played any contributory role remains unknown. Potential mechanisms by which GH elevation might theoretically affect cardiovascular risk include:

  • Increased cardiac workload from GH's effects on cardiac muscle
  • Fluid retention and increased blood volume
  • Effects on vascular endothelium
  • Metabolic changes affecting atherosclerosis progression

No causal relationship was established, but the event underscores the limitation of safety data for this compound.

FDA Safety Warnings

The FDA has flagged CJC-1295 for safety concerns in the context of compounding pharmacy use. Specifically:

  • Cardiovascular effects: "Increased heart rate and systemic vasodilatory reaction, including flushing, warmth, and transient hypotension"
  • Immunogenicity: Risk of immune reactions, potentially including anaphylaxis
  • Unknown long-term effects: Lack of extensive safety data

These warnings contributed to the decision not to include CJC-1295 in the list of approved bulk substances for pharmacy compounding.

Because CJC-1295 with DAC elevates GH and IGF-1, it carries theoretical risk for side effects associated with GH excess:

Metabolic effects:

  • Impaired glucose tolerance and insulin resistance
  • Increased risk of diabetes in susceptible individuals
  • Fluid retention and edema
  • Changes in lipid metabolism

Musculoskeletal effects:

  • Joint pain and stiffness (arthralgia)
  • Muscle pain (myalgia)
  • Carpal tunnel syndrome (with prolonged use/high doses)

Other effects:

  • Gynecomastia (breast tissue development in males) in some cases
  • Fatigue and lethargy, particularly at higher doses
  • Numbness or tingling (paresthesias)

The likelihood and severity of these effects likely correlate with dose and duration of GH/IGF-1 elevation. Individuals using high doses or with prolonged continuous elevation may face increased risk.

Tumor and Cancer Concerns

IGF-1 stimulates cell proliferation, raising theoretical concerns about cancer risk. The relationship between IGF-1 and cancer is complex:

  • Epidemiological studies show associations between higher IGF-1 levels and increased risk of certain cancers (prostate, breast, colorectal)
  • IGF-1 promotes cell survival and may inhibit apoptosis in existing cancer cells
  • However, the relationship is not simply linear—very low IGF-1 is also associated with health problems

For individuals with existing cancer or precancerous lesions, elevating IGF-1 with CJC-1295 or any GH-related intervention carries theoretical risk of promoting tumor growth. Most medical guidelines consider active malignancy a contraindication to GH therapy.

Long-term studies examining cancer incidence in populations using GHRH analogs like CJC-1295 don't exist, leaving this as a theoretical concern based on IGF-1's known biology.

Contraindications

Based on GH physiology and limited clinical data, potential contraindications to CJC-1295 with DAC include:

  • Active cancer or history of malignancy
  • Diabetic retinopathy or other proliferative retinopathy
  • Acromegaly or active GH excess
  • Known allergy to any component
  • Acute critical illness
  • Severe heart disease
  • Pregnancy and lactation (no safety data)

Medical supervision would be essential to identify contraindications and monitor for adverse effects, though such supervision is unlikely given the compound's regulatory status.

Harm Reduction Considerations

For individuals using CJC-1295 with DAC outside medical contexts, harm reduction approaches would include:

  • Starting with low doses and titrating gradually
  • Monitoring glucose levels, particularly if diabetic or pre-diabetic
  • Avoiding use if cardiovascular disease or cancer risk factors are present
  • Using sterile injection technique to prevent infections
  • Sourcing from reputable suppliers with analytical testing (though verification is difficult)
  • Discontinuing use if concerning symptoms develop
  • Not combining with multiple other hormones or drugs simultaneously

These measures reduce but don't eliminate risks associated with using a non-approved compound without medical supervision.

CJC-1295 with DAC occupies a complex regulatory space. It is not FDA-approved for any indication and cannot be legally prescribed as an approved drug. Its status for pharmacy compounding has recently changed, further restricting legal access.

FDA Approval Status

CJC-1295 with DAC has never received FDA approval. Development was discontinued in Phase II clinical trials, and no subsequent sponsor has pursued approval. This means:

  • It cannot be manufactured as an FDA-approved prescription drug
  • No legal prescribing information exists
  • Marketing it as a treatment for any condition violates federal law
  • Claims about its efficacy or safety have not been reviewed by the FDA

The compound exists in a category of "investigational peptides"—substances that reached clinical development but were never brought to market.

Pharmacy Compounding Regulations

Under FDA regulations, compounding pharmacies can prepare customized medications using bulk drug substances. Historically, some peptides not approved as finished drugs could still be used for compounding if they appeared on the FDA's "Category 2" list of substances nominated for inclusion in compounding.

CJC-1295's compounding timeline:

  • Pre-2024: CJC-1295 (with DAC), Ipamorelin, and several other peptides appeared on the Category 2 list, allowing compounding pharmacies to prepare them for prescribers
  • September 2024: The FDA removed these peptides from Category 2 after review by the Pharmacy Compounding Advisory Committee (PCAC)
  • Current status: The FDA recommended against including these substances in the final list of approved bulk substances for compounding under Section 503A

This effectively prohibits compounding pharmacies from legally preparing CJC-1295 with DAC for patients. The FDA cited safety concerns and regulatory risks in its decision.

Following removal from the compounding list, legal access to CJC-1295 with DAC is severely restricted:

What is NOT legal:

  • Compounding pharmacies cannot prepare it
  • Healthcare providers cannot prescribe it for therapeutic use
  • Vendors cannot market it as a dietary supplement
  • Companies cannot sell it with therapeutic claims

What exists in practice:

  • Research chemical suppliers may sell CJC-1295 with DAC labeled "for research purposes only"
  • Some online vendors based internationally ship to U.S. customers
  • Underground or gray-market sources supply it for enhancement purposes

These sources operate in legal gray areas or violate regulations outright. Products from such sources carry risks of contamination, incorrect dosing, or complete absence of the labeled compound.

Enforcement and Prosecution

FDA enforcement priorities typically focus on:

  • Companies making therapeutic claims about non-approved drugs
  • Compounding pharmacies violating bulk substance restrictions
  • Large-scale distribution operations

Individual possession for personal use occupies a lower priority, though technically purchasing non-approved drugs for human use violates federal law. Prosecution risk for personal use is low but non-zero.

International Status

Regulatory status varies by country:

  • Canada: CJC-1295 is not approved by Health Canada; similar restrictions apply
  • European Union: Not approved as a medicinal product; use outside clinical trials violates regulations
  • Australia: Listed as Schedule 4 (Prescription Only Medicine) in some contexts; requires prescription
  • Other countries: Status varies; many have similar restrictions on non-approved peptides

International online pharmacies may ship CJC-1295, but importing non-approved drugs carries legal and safety risks, including customs seizure.

Research Use

Legitimate research use of CJC-1295 with DAC requires:

  • Appropriate institutional approvals (IRB for human studies, IACUC for animal studies)
  • Sourcing from qualified suppliers with appropriate documentation
  • Compliance with all research regulations

"Research purposes" labeling on products sold online typically represents a legal disclaimer rather than genuine research-grade material. Authentic research-grade suppliers generally don't sell to individuals without institutional credentials.

The Practical Reality

Despite regulatory restrictions, CJC-1295 with DAC remains available through various channels. The gap between legal status and practical availability creates a situation where individuals interested in the compound must weigh legal risks, product quality concerns, and safety considerations against desired effects—without medical supervision or quality assurance typically expected of therapeutic agents.

This regulatory situation reflects broader tensions around access to experimental compounds, harm reduction for individuals who will use them regardless of legal status, and regulatory agencies' mandates to restrict unapproved drugs.

Frequently Asked Questions

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

CJC-1295 with DAC includes a maleimidopropionic acid linker that enables the peptide to bind covalently to serum albumin, extending its half-life to approximately 6-8 days and allowing twice-weekly dosing. CJC-1295 without DAC (more accurately called modified GRF 1-29) lacks this linker, has a half-life of about 30 minutes, and requires dosing 1-3 times daily. The with-DAC version creates continuous GH elevation with raised baseline levels, while the without-DAC version produces discrete GH pulses more closely mimicking natural physiology.

How long does CJC-1295 with DAC stay in your system?

The half-life of CJC-1295 with DAC is approximately 5.8-8.1 days (roughly 6-8 days). Plasma GH levels remain elevated for 6+ days after a single injection, and IGF-1 levels stay elevated for 9-11 days. After multiple doses, IGF-1 levels can remain above baseline for up to 28 days. This extended duration is due to albumin binding—the peptide circulates bound to albumin, which itself has a half-life of about 19-21 days.

CJC-1295 with DAC is not FDA-approved for any medical use and was removed from the FDA's Category 2 list for pharmacy compounding in September 2024. This means compounding pharmacies cannot legally prepare it, and healthcare providers cannot prescribe it as an approved medication. It may be available from research chemical suppliers or international vendors, but purchasing it for human use exists in a regulatory gray area or violates federal regulations. Possession for personal use is technically illegal but rarely prosecuted.

Can CJC-1295 with DAC cause cancer?

CJC-1295 with DAC elevates IGF-1 levels, and IGF-1 promotes cell proliferation and survival. Epidemiological studies show associations between higher IGF-1 levels and increased risk of certain cancers (prostate, breast, colorectal), though the relationship is complex and not simply linear. For individuals with existing cancer or precancerous conditions, IGF-1 elevation theoretically carries risk of promoting tumor growth. However, no long-term studies specifically examine cancer incidence in populations using CJC-1295, leaving this as a theoretical concern based on IGF-1's known biology rather than direct evidence of CJC-1295 causing cancer.

How much does CJC-1295 with DAC cost?

Pricing varies significantly based on source and legality. Before removal from the Category 2 compounding list, prescriptions from compounding pharmacies typically cost $200-400 per month depending on dose. Research chemical suppliers and international vendors may charge $50-150 per vial (typically 2-5 mg), with monthly costs depending on dosing protocol. However, products from these sources lack quality assurance, and actual peptide content may not match labeling. Legitimate research-grade material from verified suppliers costs significantly more and generally requires institutional credentials for purchase.

What are the side effects of CJC-1295 with DAC?

The most common side effects reported in clinical trials include injection site reactions (redness, swelling, tenderness), flushing, headache, fatigue, and occasional nausea—generally mild and transient. More concerning potential effects relate to GH elevation: impaired glucose tolerance, fluid retention, joint pain, muscle aches, and in rare cases, gynecomastia. The FDA warns of cardiovascular effects including increased heart rate, vasodilation, and transient hypotension. One death occurred during a Phase II trial, though the attending physician concluded it was unrelated to the drug. Long-term safety beyond several months is unstudied.

How do you dose CJC-1295 with DAC?

Research protocols used 30-120 mcg/kg per dose (approximately 2,100-8,400 mcg for a 70 kg person), significantly higher than doses in enhancement contexts. Compounding pharmacy protocols before regulatory changes typically suggested starting at 300-500 mcg twice weekly, with maintenance doses of 500-1,000 mcg twice weekly, spaced 3-4 days apart. Injections are administered subcutaneously in the abdomen, thigh, or upper arm. However, no FDA-approved dosing guidelines exist, and all information comes from discontinued research, compounding protocols, or anecdotal sources.

Can you combine CJC-1295 with DAC with other peptides?

CJC-1295 with DAC can be combined with growth hormone secretagogues (GHS) like Ipamorelin, GHRP-2, or GHRP-6 to amplify GH pulses through synergistic mechanisms—GHRH analogs and ghrelin receptor agonists work through different pathways that enhance each other. However, this is less common with the DAC version than with modified GRF 1-29 (without DAC) because continuous GHRH stimulation already produces sustained GH elevation. Combining multiple peptides simultaneously increases complexity, cost, and unknown interaction risks without clear evidence of proportionate benefit.

Does CJC-1295 with DAC build muscle?

CJC-1295 with DAC elevates GH and IGF-1, which theoretically support muscle protein synthesis and anabolism. However, no published clinical trials demonstrate that CJC-1295 specifically increases muscle mass in humans. Studies showing GH effects on muscle typically used recombinant GH or examined GH-deficient populations, not GHRH analog effects in individuals with normal GH secretion. While GH elevation may support muscle growth, especially combined with resistance training, direct evidence for meaningful muscle gain from CJC-1295 is lacking in the peer-reviewed literature.

How does CJC-1295 with DAC compare to Tesamorelin?

Tesamorelin is an FDA-approved GHRH analog (for HIV-associated lipodystrophy) that consists of 44 amino acids with a trans-3-hexenoic acid group providing enzymatic resistance. It has a shorter half-life than CJC-1295 with DAC (around 30-60 minutes) and requires daily subcutaneous injection. Tesamorelin produces pulsatile GH elevation rather than continuous stimulation and has established safety data from FDA trials. CJC-1295 with DAC's longer half-life offers dosing convenience (twice weekly vs. daily) but lacks approval and long-term safety studies. Tesamorelin can be legally prescribed; CJC-1295 with DAC cannot.

Bottom Line

CJC-1295 with DAC represents a sophisticated approach to extending peptide half-life through albumin conjugation, transforming a GHRH analog into a long-acting compound with an 8-day half-life. Research clearly demonstrates sustained elevation of both GH (2- to 10-fold for 6+ days) and IGF-1 (1.5- to 3-fold for 9-11 days) from twice-weekly subcutaneous injections. The peptide preserves pulsatile GH secretion while elevating baseline levels, distinguishing it from both short-acting GHRH analogs and continuous GH administration.

However, the gap between pharmacology and practical application is wide. CJC-1295 with DAC never completed clinical development—the Phase II lipodystrophy trial was halted after one participant's death, though causality was not established. No published trials demonstrate efficacy for muscle growth, fat loss, anti-aging, recovery, or other outcomes commonly claimed in enhancement contexts. The compound is not FDA-approved, was removed from the pharmacy compounding list in 2024, and cannot be legally prescribed.

The distinction between CJC-1295 with DAC and the commonly-used "without DAC" version (modified GRF 1-29) matters significantly. The DAC version creates continuous GHRH stimulation requiring twice-weekly dosing, while the short-acting version produces discrete pulses requiring daily dosing, often combined with a growth hormone secretagogue. Neither has approval, but their different physiological patterns and dosing requirements make them functionally distinct compounds despite similar naming.

For individuals considering CJC-1295 with DAC, critical limitations include:

  • Limited human safety data beyond short-term healthy adult studies
  • No efficacy data for claimed benefits like muscle growth or fat loss
  • Cardiovascular concerns flagged by FDA and highlighted by the trial death
  • Regulatory status prohibiting legal prescribing or compounding
  • Source quality issues given reliance on research chemical suppliers or underground markets
  • Long duration of effect means side effects persist for over a week

The peptide's pharmacology is compelling—albumin conjugation elegantly extends half-life, and the preserved pulsatility during continuous stimulation is physiologically interesting. But compelling pharmacology doesn't equal proven therapeutic benefit. The research shows CJC-1295 with DAC does what it's designed to do (elevate GH and IGF-1 for extended periods), but whether that translates into meaningful outcomes remains unproven.

For comparison, FDA-approved Tesamorelin offers a legal GHRH analog option with established safety data for those with a prescription-appropriate condition. For those specifically interested in peptide approaches to GH modulation through legal channels, discussing options with a knowledgeable healthcare provider would be the appropriate path—though legally available options are limited.

The broader lesson from CJC-1295's development history involves the complexity of bringing novel therapeutic peptides to market. Despite promising Phase I data and innovative technology, the compound never reached approval. Whether this was due to the trial death, commercial viability concerns, or other development challenges is unclear, but the outcome leaves a pharmacologically interesting compound without the evidence base or regulatory approval necessary for informed medical use.

Disclaimer

This article is for educational and informational purposes only. It is not medical advice and should not be interpreted as a recommendation to use CJC-1295 with DAC or any other peptide. CJC-1295 with DAC is not FDA-approved for any indication and cannot be legally prescribed by healthcare providers in the United States. The compound was removed from the FDA's pharmacy compounding list in 2024, further restricting legal access.

Using CJC-1295 with DAC or other non-approved peptides carries risks including potential side effects, unknown long-term health consequences, legal implications, and uncertainty about product quality and purity from non-regulated sources. The limited clinical research on CJC-1295 with DAC does not establish safety or efficacy for any particular use.

If you are considering peptide therapy or have questions about growth hormone modulation, consult a qualified healthcare provider who can assess your individual health status, discuss legal and evidence-based options, and provide appropriate medical supervision. Do not make health decisions based solely on information found online.

PeptideJournal.org does not sell peptides, has no financial relationships with peptide vendors, and receives no compensation for providing educational content. Our mission is to make peptide research accessible and understandable, not to promote or discourage use of any specific compound.

References

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