CJC 1295: A Peptide More Powerful Than Nature Intended.

• CJC 1295: The research, indications, research dosage, and physiology explained.

• The benefits of growth hormone supplementation in adult-onset growth hormone deficiency.

• CJC 1295 clinic trials discussed

• Comparison of CJC 1295 to Sermorelin

CJC 1295 is a very potent and long-acting growth hormone-releasing hormone (GHRH) analog. Let's break down exactly what that means and how CJC 1295 is an improved version of your natural GHRH.

GHRH is a naturally occurring peptide made in the hypothalamus. The hypothalamus is a gland that sits at the base of the brain and regulates hormone release from the pituitary gland among other functions. When growth hormone is low in the body, GHRH is released from the hypothalamus and stimulates the somatotrophic cells located in the anterior pituitary gland to synthesize and release growth hormone (GH). GH provides the following physiologic and biological changes in the body:

1) adipogenesis ( fat regulation )

2) improved sleep

3) maintenance of lean muscle mass

4) insulin regulation and

5) improved endurance.

6) increase in bone mineral density

7) improvement in quality of life questionnaires

8) increase in muscle strength

9) reduction in the risk of myocardial infarction

10) regulation of diastolic blood pressure

In humans, GH is released via 8 -10 pulses over a 24-hour period. We a consider GH to be a pulsatile hormone, released in waves over time. The biological effects of GH on cells, tissues, muscles, and organs are principally mediated by IGF -1 and we measure IGF-1 in the body to determine GH levels and pulsatility. GHRH is a key contributor to the regulation of GH and IGF-1 levels in the body.

HGH injections is a medication utilized to improve GH in human, but it is not natural. In the situation of a patient injection of exogenous GH, a patient's natural production will reduce because the body senses there is too much GH present. Exogenous HGH is only approved for a narrow subset of medication conditions, namely short stature in children to provide growth, Turner syndrome, Noonan syndrome, Prader-Willi syndrome, short stature homeobox-containing gene (SHOX) deficiency, and chronic renal insufficiency. In 2020 the FDA approved Sogroya® (somapacitan-beco) a human growth hormone analog indicated for the replacement of endogenous growth hormone in adults with growth hormone deficiency.

CJC 1295 is a peptide that mimics the actions of GHRH. What makes CJC 1295 unique is its ability to increase your natural GH release in a pulsatile manner without reducing any negative feedback loops that would otherwise interfere with GH release.

CJC 1295 has several benefits compared to native GHRH that include:

i) CJC 1295 is longer acting than native GHRH.

ii) CJC 1295 has a longer half-life than GHRH ( 8-10 days for CJC 1295 vs 10-12 min for iv GHRH).

iii) CJC 1295 does not impair or affect the natural pulsatile release of GH.

iv) CJC 1295 has a higher binding affinity to the GHRH receptor.

The potency of CJC 1295, lends itself to the construction of the peptide by key substitutions at the 8,15,27, and 2 positions along the amino acid chain. Such substitutions provide a more stable CJC 1295 peptide thereby:

i) reducing oxidative degradation

ii) preventing proteolytic cleavage

iii) prolonging the half-life of the peptide

iv) enhancing bioavailability

In addition, CJC 1295 is a much more potent and longer-acting GHRH analog compared to Sermorelin. Sermorelin is a commonly used peptide provided to treat patients with growth hormone deficiency when other alternative measures have failed and/or confirm a diagnosis of GH deficiency. Sermorelin has a half-life of 30 minutes while CJC-1295 has a half-life of more than a week. In preliminary studies, the safety, efficacy, and tolerability of injecting 125ug/kg of CJC 1295 were found to cause significant increases in GH and IGF levels in human subjects. Clinical studies by Treichman SL et. al. revealed A 60-ug/kg dose of CJC 1295 resulted in GH levels of 125% and IGF-I levels of 80%. In studies by Lonescu et.al on male subjects who received CJC 1295 no serious adverse effects were observed. The most observed effects were a change in heart rate that was dose-dependent and transient redness and tenderness at the injection site. No human subjects experienced any of the adverse effects commonly associated with exogenous human growth hormone therapy.

A 2009 study by Lucila Sackmann Sala et al, studied the effects of CJC 1295 to increase growth hormone and IGF-1 levels in male subjects and identifying protein biomarkers in response to increased growth hormone levels. In the study, 11 healthy young male adults were administered a single dose of CJC 1295 via subcutaneous injection. The administered dose of CJC 1295 was 60-90 ug/kg. Serum was measured and analyzed one week before and after the injection. Within the serum, 192 spots ( a group of proteins) were measured and observed for post-translational modifications that would be detected on 2D gels. Of the 192 spots, only 97 spots were found to be present in all subjects. Of the 97 spots, 5 spots were found to display significant intensity differences between serum measured before and after subcutaneous injection of CJC 1295. Figure I and II adapted from Sackman et al. research paper represents a 3D modeling of the 5 spots before and after CJC 1295 injection.

As you can see in the far left column demonstrating different protein changes revealed by topographic changes indicated by the arrow. The 5 spots were then further investigated for their identity using tandem mass spectrometry. The 5 spots (A-E) were identified as:

A) Apoliprotein A1 (ApoA1),

B) Albumin and Immunoglobin Fragment

C) Transthyretin (TTR)

D) Beta- Hemoglobin

E) Albumin Fragment

The proteonomic analysis of the 5 spots (proteins A-E) demonstrates the potential for using proteonomic changes as biomarkers to detect elevated levels of GH in male subjects for therapy monitoring or drug sport testing. In addition, the study conveyed that serum GH and IGF-1 levels increased one week after a single administration of CJC 1295, confirming previous trial findings.

From clinical research trials to date, CJC -1295 is a GHRH analog that is more potent than native GHRH. CJC 1295 has been used in human subjects via clinical trials with documented safety and efficacy to raise GH levels.

1. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. 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. Epub 2009 Apr 21. PMID: 19386527; PMCID: PMC2787983.

2. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne J-P, Frohman LA 2006 Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analogue of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab 91:799–805

3. Díez JJ, Sangiao-Alvarellos S, Cordido F. Treatment with Growth Hormone for Adults with Growth Hormone Deficiency Syndrome: Benefits and Risks. Int J Mol Sci. 2018 Mar 17;19(3):893. doi: 10.3390/ijms19030893. PMID: 29562611; PMCID: PMC5877754.