Studies indicate that CJC-1295 and GHEP-2 work through other receptors, but they can in combination enhance release of growth hormone (GH) from the anterior pituitary.
CJC-1295 is a GHRH receptor binder that stimulates pituitary cells to discharge GH. It’s made from GHRH 1-29-the biologically active 29-amino acid piece-and contains tetra substitutions along with a drug-affinity complex (DAC). The DAC component binds plasma proteins and seems to prolong CJC-1295’s half-life of action.
GHRP-2 peptide on the other hand, is a hexapeptide. It is a ghrelin (GHS-R1a) receptor agonist present in the hypothalamus and pituitary. Activation of GHS-R1a has been reported to induce release of GH secretion in GHS-R1a-expressing pituitary cells.
As stimulators of various receptors and pathways, CJC-1295 and GHRP-2 are postulated to act synergistically to increase anterior-pituitary GH release more than either peptide alone.
CJC-1295 & GHRP-2 Blend and Growth Hormone Secretion
Research indicates that GHRP-2 is tightly bound to the GHS-R1a (ghrelin) receptor at the pituitary and hypothalamus, whereas CJC-1295 is directed towards the GHRH receptor at a pituitary. The combination has been found to increase plasma GH and promote total GH release. There also what appears to be a sustained-release activity of the blend prolonging peptide half-life, resulting in prolonged GH secretion in comparison to both peptides alone. In reports, basal GH increased ~7.5-fols, and for a total increase in GH secretion of ~46%.
Though they possess separate receptors for their action, the two work synergistically to enhance pulsatile GH release that is still within normal negative feedback-something that would perhaps prevent supratherapeutic levels of GH from occurring and its consequent effects.
Based on this, scientists hypothesize synergy between GHRH mimetics like CJC-1295 and secretagogue GHRP-2. The combination in a study resulted in a ~54-fold rise of pulsatile GH over controls. GHRP-2 reduced time to peak GH by a median 43%. Tested alone, GHRP-2 resulted in a ~47-fold rise of pulsatile GH, while GHRH mimetics alone produced approximately a ~20-fold rise.
CJC-1295 & GHRP-2 Mix and Fat and Muscle Metabolism
GHRP-2 and CJC-1295 both seem to increase pituitary GH through mechanisms that are distinct from each other, which may be useful for fat loss. CJC-1295 also seems to be longer-lived than native GHRH. GH itself may have anti-obesity effects by inducing lipolysis, increasing utilization of fatty acid as fuel, and increasing fat oxidation.
Description of the blend has documented finding augmented hepatic glucose production with inhibited glucose uptake, a profile which can shift the body to fat burning and storage. Ghrelin-releasing peptides like GHRP-2, “due to its bimodal actions on … (hGH) and energy balance,” could function as the widespread hormonal cue of nutrition status to the somatotropic axis, bridging growth with energy balance.
As a ghrelin analogue, GHRP-2 could potentially drive appetite. The mechanism is suggested to be through activation of the GHSR-1a receptor in the hypothalamus, pituitary, and stomach, which results in signals that enhance neuropeptide Y (NPY) and agouti-related peptide (AgRP)-the former and latter both being important in energy balance and appetite. Concurrently, GHRP-2 will also inhibit the anorexigenic hormone α-MSH, further tipping towards appetite. It could also affect the mesolimbic reward system via GHSR-1a, possibly reinforcing drive for tasty food.
Early investigations even report subtle weight gain. Due to their ubiquitous presence and the multifunctional role oh ghrelin, GHRP-2’s action on appetite probably has interactions with the involvement of other hormones, neural input, circadian signals, and body states.
Net effect: enhanced energy intake through GHRP-2 can counteract part of the fat-reducing action of CJC-1295. CJC-1295 + GHRP-2 will enhance anabolic signaling, though, so a better candidate for study of weight gain-particularly lean mass, than for single fat-loss protocols, possibly through IGF-1-mediated mechanisms.
CJC-1295 & GHRP-2 and IGF-1
CJC-1295 and GHRP-2 blend can prompt the liver to release insulin-like growth factor-1 (IGF-1) through increasing growth hormone (GH). The process is as follows: GH binds its receptor on hepatocytes, activates the JAK-STAT pathway, the activated STAT proteins move into the nucleus, bind response elements, and activate the IGF-1 gene. Freshly produces IGF-1 then circulates in the blood and acts on target tissues.
IGF-1 is a powerful growth mediator that is believed to be responsible for most of the anabolic effects of GH. It stimulates cell and tissue growth, protein synthesis, organ and skeletal muscle hypertrophy.
In test models, even short exposure to CJC-1295 has changed mean plasma GH, resulting in a 2- to 10-fold increase for a period of approximately six days (or more). GH peaks are usually 1-4 hours after administration. CJC-1295 has also been associated with dose dependent 1.5-to 3-fold mean plasma IGF-1 elevations for 9-11 days. At greater exposure, IGF-1 can be sustained at least two weeks; following multiple dosing means IGF-1 has been sustained above baseline through 28 days. Interestingly, a cumulative effect is observed following 2-3 administrations, with GH and IGF-1 still above baseline on day 14 in the laboratory.
References:
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