CJC-1295 (DAC GRF, Drug Affinity Complex GRF)

Description:

CJC-1295 is a synthetic growth hormone secretagogue. It specifically belongs to the growth hormone releasing hormone (GHRH) family of drugs. These compounds all mimic the effects of endogenous GHRH, a 44-amino acid hypothalamic peptide hormone that stimulates the release of growth hormone from the pituitary gland. CJC-1295 is actually a very long acting GHRH analog. Whereas native GHRH has a half-life measured in minutes, which reduces its practicality as a therapeutic agent, CJC-1295 is capable of sustained increases in growth hormone and IGF-1 with as little as once per week administration. This drug is used in the fitness community for the support of muscle growth and fat loss, as well as its potential anti-aging properties.

As mentioned, CJC-1295 is a slow acting GHRH analog. Its half-life ranges from 8-10 days in humans.1 This is due to its high affinity for compartmentalizing with serum albumin, a binding protein. About 90% of injected CJC-1295 winds up bound to albumin, which acts as a distribution vehicle. It provides a slow release of hormone back into free circulation over several weeks. The slow activity of CJC1295 is reflected in its pharmacokinetic profile. One human study found a single injection (30, 60, 125, or 250 mcg/kg) to elevate serum growth hormone 2 to 10 fold for up to 6 days. Serum IGF-1 levels also rose by 1.5 to 3 fold in this same study, which persisted for up to 2 weeks.

CJC-1295 does not significantly influence peak levels of GH or IGF1. It also does not appear to influence the number of GH/IGF-1 peak episodes per day (GH is released in pulses, usually 8-10 daily). These measures all remain stable during therapy. We note this is a second study, where researchers did reported a nearly 50% increase in total GH and IGF-1 secretion after administration of 6090 mcg/kg.2 Looking very closely at the timing and levels though, they found the increase was in basal secretion. That is, the lows or ‘trough levels’ of hormone that occur in-between GH pulses. With CJC-1295, your ‘low periods” are significantly higher. . GHRH and ghrelin are the two primary positive regulators of growth hormone secretion in humans. These two hormones are the core focus of drugs of the GHRH and GHRP class, respectively. It is of note that GHRH analogs tend to display more specificity for growth hormone release than GHRPs. That is because endogenous GHRH has less activity in other areas as compared to ghrelin, which seems to influence a more diverse set of systems. Studies examining the pharmacodynamics of CJC-1295 confirm this. They find it has no acute effect on cortisol, prolactin,

LH (luteinizing hormone), or TSH (thyroid stimulating hormone). Thus, we consider CJC-1295 a ‘selective’ GH secretagogue, with a low likelihood of spillover side effects.

Note: The research designation for this compound is CJC1295. Its structure includes a drug affinity complex (DAC). Likewise, referring to this as ‘CJC-1295 with DAC” is incorrect. All CJC-1295 has DAC. CJC1295 without DAC is the drug Mod GRF 1-29.

Key Points:

• Very Long Acting

• Moderate Effect on GH

• Influences Basal Secretion

• No effect on Peak Amplitude, Frequency

• High Specificity for GH

History:

CJC-1295 was first described in 2005 by Jette et al.3 The drug was under the development of ConjuChem in Montreal, Canada, which appeared focused on introducing it as a pharmaceutical product. During the mid 2000s, a series of Phase I/II clinical trials were announced on CJC1295. The drug was being investigated for the treatment of growth hormone deficiency, as well as the treatment of lipodystrophy associated with HIV infection. However, ConjuChem abruptly discontinued their lipodystrophy study in 2006 after the death of one participant. It is unclear if there was any relationship to the drug.

One unconfirmed report has the subject dying shortly after receiving their 11th injection.4 Further research on CJC1295 seems to have stalled at this point. The future of this agent as a pharmaceutical product remains unclear.

CJC-1295 is on the World Anti-Doping Agency’s (WADA) list of prohibited substances. Methods for detecting the misuse of this compound are available.5

Structural Characteristics:

CJC-1295 is a tetrasubstituted derivative of GRF 1-29 (sermorelin). It differs by the substitution of four amino acids, as well as the addition of a reactive maleimidoproprionic acid group. This group covalently binds the protein to serum albumin, greatly extending its half-life in the body. The specific structure of CJC-1295 is Tyr-DAla-Asp-Ala-lle-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-ValLeu-Ala-Gln-LeuSer-Ala-Arg-Lys-Leu-Leu-Gln-Asp-lleLeu-Ser-ArgLys(Maleimidopropionyl)-NH2

Warnings:

CJC-1295 is an unapproved new drug. A thorough understanding of its safety and propensity for side effects in humans is lacking at this time.

This drug should never be used during pregnancy, with cancer, a history of cancer, diabetic retinopathy, sclerosing diseases of the liver or lungs, intracranial hypertension, or uncontrolled diabetes.

How Supplied:

CJ-1295 is not available as a pharmaceutical product. No standard dosage information is available.

This drug can be purchased as a research compound or gray market supplement only. It is typically supplied in multi-dose vials containing 2mg or 5mg of dry lyophilized powder. This must be reconstituted with saline or bacteriostatic water before use. All unused portions of this drug should be kept under refrigeration

Side Effects (General):

Common side effects to CJC-1295 include flushing, warmth, dizziness, and transient hypotension following injection. Other common side effects include headache, diarrhea, nausea, and abdominal pain. Many side effects are dose dependent. In studies this drug appeared to be especially well tolerated at doses of 30 and 60 mcg/kg, while more significant side effects were noted with 125 and 250 mcg/kg doses. Also frequently reported are adverse effects typically associated with other types of growth hormone therapy, such as water retention (edema), joint pain (arthralgias), carpal tunnel syndrome, and numbness or tingling in the extremities.

Note that the incidence of GH-related side effects tends to be lower with GHRP therapy as compared to traditional hGH.This is because GH/IGF-1 release is subject to the limits of endogenous synthesis, and as such the drug is less amenable to overdosing.

Side Effects (Injection site):

The subcutaneous administration of this drug may cause redness, itching, pain, or lumps at the site of injection. Injection site reactions occurred in approximately 70% of subjects receiving CJC-1295 by subcutaneous injection in one study.

Side Effects (Impaired glucose tolerance):

This drug may impair glucose tolerance and raise blood sugar levels. This may occur in individuals without preexisting diabetes or impaired glucose tolerance.

Administration:

CJC-1295 may be given by subcutaneous or intramuscular injection, or IV infusion. The subcutaneous route is most often applied.

This drug has not been approved for use in humans. Prescribing guidelines are unavailable.

When used for physique- or performance-enhancing purposes, CJC1295 is generally administered at a dosage of 1000-2000 mcg (1-2 mg). This is given 1-2 times per week. Cycles usually last 3-4 months, though programs of 6 months or longer are not uncommon. During investigatory studies with this drug, significant antibody formation (which might reduce the effectiveness of CJC1295) was not reported. This suggests that desensitization is not likely to be rapid, if it does occur.

During clinical studies, CJC-1295 seemed to exert its optimal effect (tolerance, benefits) at a dosage of 30-60 mcg/kg. This was administered once every 7 or 14 days. The calculated amount would be roughly 2.5 to 5 mg for someone weighing 85 kg, which is similar to the common cumulative dosage range of CJC-1295 in the fitness community. Higher doses (up to 250 mcg/kg or 20 mg total for someone weighing 85 kg) were also well tolerated in studies, but with a higher incidence of side effects

Combination Therapy:

CJC-1295 (a GHRH) may be combined with a drug from the GHRP (Growth Hormone Releasing Peptides) class, such as such as GHRP-2, GHRP-6, hexarelin, ipamorelin, or MK-677. These two drug types alter GH release through distinct and complimentary mechanisms

Such combination therapy tends to produce substantial synergy with regard to GH release.

Availability:

CJC-1295 is not available as a prescription drug product. It is sold exclusively as a ‘research compound” or gray market supplement. Note that the quality of gray market products can be difficult to assure.

1 Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor 1 Secretion by CJC-1295, a Long-Acting Analog of GHReleasing Hormone, in Healthy Adults. Sam L. Teichman et al. J Clin Endocrinol Metab 91:799–805, 2006

2 Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog. Madalina Ionescu and Lawrence A. Frohman. J Clin Endocrinol Metab 91:4792–4797, 2006.

3 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. Lucie Jette et al. Endocrinology 146:3052-3058, 2005

4 Lipodystrophy study halted after patient death. Edwin Berbard. July 31, 2006. Aidsmap.com

5 Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions. Thevis M et al. Expert Rev Proteomics. 2014 Dec;11(6):663-73