CJC-1295 Overview & Comparison To Other GHRP & GHRH Peptides

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What is CJC-1295 | How Does CJC-1295 Work? | CJC-1295 Benefits | CJC-1295 & Bodybuilding | CJC-1295 & Ipamorelin | CJC-1295 VS GHRP-2 & -6 | CJC-1295 VS Sermorelin | CJC-1295 Dosage | CJC-1295 Side Effects | CJC-1295 Review

Human growth hormone (GH) is known for its effect on growth, as well as on improving lean body mass and performance.

Approval of GH use is restricted to specific medical purposes, as the side effects of flooding the body with large amounts of GH can be severe. Therefore, using molecules that regulate the body’s own GH production offer a safe alternative.

The peptide CJC-1295 is  very effective in upregulating GH levels throughout the body, without disturbing the natural balance.

This reduces the risk of unwanted effects, while providing all the benefits of elevated GH levels.

 

CJC-1295 as a Growth Hormone Alternative

The human growth hormone (GH) is produced by the pituitary gland, a very small compartment of the brain located adjacent to the hypothalamus.

GH is the major hormone produced by and released from the pituitary gland, and is mainly responsible for growth during childhood and adolescence.

Activation and release of GH is tightly regulated by hormones and peptide regulators from the nearby hypothalamus.

While GH releasing hormones (GHRH), such as CJC-1295, trigger GH production and release, somatostatins, which are also produced by the hypothalamus, limit or inhibit GH release, thereby tightly regulating the intricate balance of GH function.

GH gets released in distinct pulses throughout the day, thereby activating downstream molecules such as IGF-1 (insulin-like growth factor 1).

GH has been approved by the FDA and other international regulatory bodies for the treatment of children with growth defects and GH deficiencies, as well as for adults with GH deficiency, HIV-associated lipodystrophy, and other disorders.

Typically, GH is administered once daily in the form of recombinant human GH. However, injection of a daily dose of GH does not resemble the pulsatile pattern in which GH is naturally released, which could lead to side effects and make it less – or more – effective, making it difficult to choose the appropriate dosage.

Use of regulatory molecules such as GHRHs may therefore offer a safe and useful alternative.

The GHRH analog CJC-1295 is a peptide that is more stable than GH, and has been shown to activate natural pulsatile GH release over a week after a single injection in healthy men[1].

CJC-1295 may therefore be an interesting and powerful alternative to using GH in medical applications.

 

What is CJC-1295

CJC-1295 is a synthetic peptide similar to naturally occurring GHRHs. The molecule has been modified so that it binds to albumin protein in the body.

This binding significantly increases the stability of CJC-1295 up to 8 days in the body, giving CJC-1295 a great therapeutic advantage over natural GHRHs, which are unsuitable for medical use due to their extremely limited bioavailability[2].

 

How Does CJC-1295 Work?

CJC-1295 activates GH release from the pituitary gland, as well as downstream increase of IGF-1 levels.

The effectiveness of CJC-1295 in promoting GH activation has been confirmed in animal models.

Mice which were deficient in growth due to a lack of GHRHs were injected with CJC-1295 once a day. Use of CJC-1295 led to full restoration of growth, which means that these mice grew to the same size as they littermates who had normal GHRH levels.

In addition, injection of CJC-1295 also restored the amount of lean body mass and subcutaneous fat, showing that CJC-1295 is able to promote bone growth as well as increase muscle mass and body weight[3].

Importantly, CJC-1295 activates increased GH release without disturbing the pulsatile pattern of release.

A single injection of CJC-1295 in healthy men led to a 46% increase in GH production, which was still evident a week after administration.

While GH and IGF-1 levels were increased, the pattern of GH release was similar to that of natural GH release during growth phases[4].

These findings clearly show that CJC-1295 is stable and long-term acting in human adults.

 

CJC-1295 Benefits

Although CJC-1295 has been investigated in very few human studies so far, its favorable safety and effectiveness profile may make it a useful medical compound for future studies and applications.

Due to its confirmed long-term activity on activating the body’s own GH and IGF-1, CJC-1295 may be considered a safe and long-term activating alternative to GH or GHRH use.

Benefits of CJC-1295 should therefore be comparable to those achieved by related compounds, such as ipamorelin or MK-677. Potential benefits may include:

 

CJC-1295 & Growth

Child Growth Chart

Changes in GH levels are primarily associated with longitudinal growth, making bones longer and leading to an increase in size. As longitudinal growth is terminated at the end of puberty by closure of the growth plates, GH is unable to trigger bone growth in adults.

CJC-1295 has clear involvement in promoting growth in GH deficient and growth retarded animals, and could therefore be considered a safe substitute for the use of GH or IGF-1[3].

 

CJC-1295 & Ageing

DNA Molecule Representing Anti-aging Concept

After a peak at the end of the adolescent growth phase, GH and IGF-1 levels decline during the ageing process. This is accompanied by a loss in muscle mass and muscle strength, which may lead to sarcopenia (significant loss of muscle mass) and frailty.

Reversal of the GH decline is therefore a much investigated area, with the aim to slow down the ageing process, or to lessen the burden of ageing.

As other GH regulators, including the GH secretagogue MK-677 have been shown to be able to increase GH and IGF-1 levels in older adults, as well as to increase lean body mass, it is feasible to consider that CJC-1295 may have similar effects on  body condition during ageing[5].

Confirmation of these presumptions is still outstanding, awaiting future clinical studies to investigate the role of CJC-1295 during ageing.

 

CJC-1295 & Bodybuilding

Flexing Muscles Working Out

CJC-1295 belongs to the substances that are prohibited and tested for by regulatory bodies, as it is not approved as a performance enhancing drug.

CJC-1295 may still be useful for those not competing in order to build muscle and increase lean body mass.

While the effectiveness of CJC-1295 on improving performance and muscle mass in athletes has not been confirmed yet, some results from clinical trials indicate its potential usefulness.

CJC-1295 clearly activates GH release, as several biomarkers for GH activity were identified in human samples one week after use of CJC-1295.

It can therefore be presumed that CJC-1295 use would trigger similar anabolic effects to those seen with GH use, but may have a more favorable safety and side effect profile.

As CJC-1295 does not disturb the normal GH release cycle, but increases the amount of GH that is released, side effects should be minimal if used in recommended doses, which have been proven safe and effective by clinical studies in healthy adults[2].

 

Combination of CJC-1295 & Ipamorelin

Male fat and slim concept

Effectiveness of different compounds can be enhanced by a successful combination of two or more molecules. This may be the case for using CJC-1295 together with ipamorelin.

Ipamorelin is a short synthetic peptide that mimics the effects of the GH releasing peptide (GHRP) ghrelin.

Just like ghrelin, ipamorelin binds to ghrelin receptors throughout the body, thereby triggering the release of GH from the pituitary gland.

Ipamorelin as a highly selective agent, which means that it specifically activates GH, but no other hormones, such as ATCH (adrenocorticotropic hormone) or cortisol. This reduces the risk of unwanted side effects, and increases effectiveness, as the drug is not “diluted” by performing other (unwanted) tasks.

CJC-1295 is similarly specific in its activation of GH, as it does not activate prolactin, cortisol or other agents that are typically released due to GHRH activity.

The reason for the potentially exponential combinatorial effect of these two compounds lies in the fact that they activate GH via distinct pathways.

By binding to distinct receptors, the combination of CJC-1295 and ipamorelin has the ability to increase GH release and activity in an additive or even exponential manner, leading to a several-fold increase in GH concentration.

linical studies have shown that the combination of a GHRH and a GHRP can increase GH levels up to 10-fold.

However, the study also showed that this significant increase only occurred in about 40% of the patients, whereas the GH levels were actually lower than expected with a single compound in the remaining study participants[6].

It may therefore be a reasonable approach to measure GH levels shortly after the first use of the combination of CJC-1295 and ipamorelin to confirm effectiveness in each individual.

 

Comparison of CJC-1295 to GHRP-2 & GHRP-6

Using CJC-1295 has distinct advantages over the use of traditional GHRPs such as GHRP-2 or GHRP-6. Both of these have very limited bioavailabilities, so that once injected, they get degraded and lose their activity quickly.

GHRP-6 has a half-life of 20 minutes, indicating that 20 minutes after injection its activity has reached 50%.

In addition, traditional GHRPs have poor oral availability. Only 0.3% or GHRP-6 taken orally reaches its target receptors[7].

CJC-1295 in contrast has a bioavailability of more than a week after administration.

Furthermore, CJC-1295 is a more potent activator of GH and IGF-1. Taken together, the much higher effectiveness of CJC-1295 makes it safer and more cost effective, as much less compound has to be used to achieve similar results.

 

Comparison of CJC-1295 VS Sermorelin

Sermorelin is, like CJC-1295, a modified GHRH. Traditionally, sermorelin has been used for the treatment of growth-deficient children in the US, and promoteds longitudinal growth.

However, the half life of sermorelin is around 10 minutes, while that of modified CJC-1295 is around a week.

Compared to sermorelin, CJC-1295 can therefore be used less frequently and/or in lower doses than sermorelin with similar effectiveness, making CJC-1295 the preferred compound.

 

CJC-1295 Dosage

Clinical data on the use of CJC-1295 in humans is limited, but dosages of 30 to 60 µg/kg body weight were considered safe and effective in the activation of GH.

In the same study, dosages up to 250µg/kg have been tested with no serious adverse events reported[2]. The optimal time to use CJC-1295 is in the late evening.

 

CJC-1295 Side Effects

Follow-up studies of up to 49 days after CJC-1295 injections in healthy adults showed that CJC-1295 was safe and well tolerated, especially at 30 to 60 µg/kg bodyweight.

During this study, no serious adverse events were reported, indicating that CJC-1295 is a safe compound[2]. Long-term safety data however still requires confirmation.

 

CJC-1295 Review

CJC-1295 is an effective and safe synthetic analog of human GHRH.

While data on its efficacy in humans is limited, evidence has shown that it is a potent activator of GH release, triggering benefits associated with increased GH levels, including growth during childhood and adolescence, increase in lean body mass and improvements in peak performance.

In comparison to traditional GH activators and peptides, CJC-1295 has dramatically increased stability and bioavailability, which means that use of this compound can be less frequent with equal effectiveness.

In addition, use of CJC-1295 with synergistic partners that activate alternative GH pathways may be useful to optimize GH level increase.

 

References:

[1] Sackmann-Sala L, Ding J, Frohman LA. 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 Dec;19(6):471-7. [DOI: 10.1016/j.ghir.2009.03.001]

[2] Teichman SL, Neale A, Lawrence B. 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 Mar;91(3):799-805. [DOI: 10.1210/jc.2005-1536]

[3] Alba M, Fintini D, Sagazio A. 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 Dec;291(6):E1290-4. [DOI: 10.1152/ajpendo.00201.2006]

[4] 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 Dec;91(12):4792-7. [DOI: 10.1210/jc.2006-1702]

[5] Nass R, Pezzoli SS, Oliveri MC. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008 Nov 4;149(9):601-11. [PMCID: PMC2757071]

[6] Leal-Cerro A, Garcia E, Astorga R. Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency. Eur J Endocrinol. 1995 Jun;132(6):712-5. [PMID: 7788011]

[7] Sigalos JT, Pastuszak AW2. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev. 2018 Jan;6(1):45-53. [DOI: 10.1016/j.sxmr.2017.02.004]

Nina Bausek, PhD, MSc
Nina Bausek, PhD, MSc, is a geneticist with a research background in reproductive biology, oncology and hematology, who is currently working as a medical adviser, writer, and entrepreneur. Her mission is to improve health and fitness by spreading knowledge and supporting evidence-based methods. She currently lives in Vienna, Austria.