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GHRP And CJC-1295 Dosing
By: REP
Growth Hormone Releasing Hormone CJC-1295
CJC-1295 Dosing:
Growth Hormone Releasing Hormone (GHRH) CJC-1295 is a synthetic secretalogue, when injected stimulates HGH release from the hypothalamus. Dosing GHRH once at night for anti-aging purposes and multiple injections (1-3x) for anabolism. CJC-1295 has the ability to make the body produce its own GH as compared to using synthetic HGH. GHRP-6 use in conjunction with CJC-1295 is synergistic, amplifying the GH pulse considerably.
CJC-1295 is typically found in 2mg vials. Reconstitute with BW. Inject subcutaneously.
Researchers report positive effects much like that of HGH. Particularly energy, quality sleep, fat loss/metabolism, improved skin quality, pumps in the gym.
Most common desirable form to find and research with CJC-1295 (Growth Hormone Releasing Factor) is a modified GRF (1-29), lacking the DAC (drug affinity complex). This GHRH has a short half life. Post injection flush is common.
Growth Hormone Releasing Peptide (GHRP-6)
GHRP-6 (Growth Hormone Releasing Peptide) Dosing:
Light: 50mcg
Common: 100mcg
Large: 150mcg
Growth Hormone Releasing Peptide (GHRP-6) is a peptide in the growth factor family composed of six amino acids. It has strong effect on the release of Human Growth Hormone (HGH). Dosed at night for anti-aging purposes and multiple times throughout the day for anabolism. GHRP is often used in conjunction with GHRH CJC-1295 to amplify GH pulse. GHRP-6 peptide is typically offered in 5mg vials.
GHRP can be used effectively in the treatment of GH deficiency. Main use is to promote food intake by stimulating hunger and aid in energy metabolism. The major side effect being a significant increase in appetite due to a stimulating the release of Ghrelin, a hormone released naturally in the lining of the stomach and increases hunger and gastric emptying.
Benefits of increased HGH levels through GHRP-6 stimulation include: an increase in strength, muscle mass and body fat loss, rejuvenation and strengthening of joints, connective tissue and bone mass. Enhanced HGH secretion also leads to the liver secreting more IGF-1, which is thought to be the primary anabolic mechanism of action for Growth Hormone.
Mixing: Bacteriostatic water is used for reconstitution. When diluted, peptide lasts a very long time when left alone in the refrigerator (months).
Example- 2.5ml(cc) bacteriostatic water per 5mg GHRP vial equates to a 100mcg dose approximately each 2-3 marks on a U100 insulin syringe.
Example- 5ml(cc) bacteriostatic water per 5mg GHRP vial equates to a 100mcg dose approximately every 5 marks on a U100 insulin syringe.
Dosing: The saturation dose of GHRP-6 has been determined to be around 100mcg
5mg GHRP = 5,000mcg
5,000mcg/100mcg = 50 100mcg GHRP doses per 5mg
GHRP-6 may be the most cost effective secretalogue available today.
And some more
What is growth hormone?
Synthetic Growth Hormone is an artificially created hormone "identical" to the major naturally produced (endogenous) isoform. It is often referred to by its molecular mass which is 22kDa (kilodaltons) and is made up of a sequence of 191 amino acids (primary structure) with a very specific folding pattern that comprise a three-dimensional structure (tertiary structure). This tertiary structure is subject to potential shape change through a process known as thermal denaturation. While many labs are capable of generating growth hormone (GH) with the proper primary structure not all will be capable of creating a tertiary structure identical to the major naturally occurring growth hormone. The tertiary structure can determine the strength with which the growth hormone molecule binds to a receptor which will in turn affect the "strength" of the intracellular signaling which mediates the events leading to protein transcription, metabolism, IGF-1 creation, etc. It is this inconsistency that accounts in part for the differences in effectiveness of various non-pharmaceutically produced synthetic growth hormone.
Naturally produced Growth Hormone is produced in the anterior pituitary and to a far lesser extent in peripheral tissue. It is made up of a blend of isoforms the majority of which is the 22kDa (191 amino acid) variety with which most are familiar. In addition an isoform that is missing the 15 amino acids that interact with the prolactin receptor is also produced. This form is known as 20kDa and although it binds differently to the growth hormone receptor it has been shown to be equally potent to 22kDa. It appears that 20kDa has lower diabetogenic activity then 22kDa. The pituitary releases a blend of these two isoforms with 20kDa averaging perhaps 10% of the total although this percentage increases post-exercise. Currently there is no synthetic produced for external administration for this isoform.
Growth hormone (GH) in the body is released in pulsatile fashion. It has been demonstrated that this pattern promotes growth. The pituitary is capable of rather quickly synthesizing very large amounts of growth hormone which it stores large amounts in both a finished and unfinished form. Adults rarely experience GH pulses (i.e. releases of pituitary stores) that completely deplete these stores. As we age we do not lose the ability to create and store large amounts of growth hormone. Rather we experience a diminished capacity to "instruct" their release. The volume of GH that is released can not be properly equated to the exogenous administration of synthetic GH for the reason that a set of behavioral characteristics accompany natural GH that differ from those of synthetic GH. Among those characteristics are concentrated pulsatile release which upon binding in mass to growth hormone receptors on the surface of cells initiate signaling cascades which mediate growth events by translocating signaling proteins to the nucleus of the cell where protein transcription and metabolic events occur.
These very important signaling pathways desensitize to Growth Hormone's initiating effects and need to experience an absence of Growth Hormone in order to reset and be ready to act again. The presence of GH released in pulsatile fashion is graphed as a wave with the low or no growth hormone period graphed as a trough. Therefore attempting to find a natural GH to synthetic GH equivalency is not very productive because in the end what is probably import is:
- the quantity & quality of intracellular signaling events; and
- the degree to which GH stimulates autocrine/paracrine (locally produced/locally used) muscle IGF-1 & post-exercise its splice variant MGF.
Synthetic GH versus Natural GH in IUs
An attempt has been made on my part and can be found at:
#8 - Growth Hormone Administration vs. CJC-1295/GHRP-6 + GHRH (part I of II)
#9 - Growth Hormone Administration vs. CJC-1295/GHRP-6 + GHRH (part II of II)
Rather than demonstrate absolute values this comparison articles should serve to demonstrate that the body can produce pharmacological levels of growth hormone.
Brief overview of natural GH release
The initiation of growth hormone release in the pituitary is dependent on a trilogy of hormones:
Somatostatinwhich is the inhibitory hormone and responsible in large part for the creation of pulsation;
Growth Hormone Releasing Hormone (GHRH)which is the stimulatory hormone responsible for initiating GH release; and
Ghrelin which is a modulating hormone and in essence optimizes the balance between the "on" hormone & the "off" hormone. Before Ghrelin was discovered the synthetic growth hormone releasing peptides (GHRPs) were created and are superior to Ghrelin in that they do not share Ghrelin's lipogenic behavior. These GHRPs are GHRP-6, GHRP-2, Hexarelin and later Ipamorelin all of which behave in similar fashion.
In the aging adult these Ghrelin-mimetics or the GHRPs restore a more youthful ability to release GH from the pituitary as they turn down somatostatin's negative influence which becomes stronger as we age and turn up growth hormone releasing hormone's influence which becomes weaker as we age.
The exogenous administration of Growth Hormone Releasing Hormone (GHRH) creates a pulse of GH release which will be small if administered during a natural GH trough and higher if administered during a rising natural GH wave.
Growth Hormone Releasing Peptides (GHRP-6,GHRP-2,Hexarelin) are capable of creating a larger pulse of GH on their own then GHRH and they do this with much more consistency and predictability without regard to whether a natural wave or trough of GH is currently taking place.
Synergy of GHRH + GHRP
It is well documented and established that the concurrent administration of Growth Hormone Releasing Hormone (GHRH) and a Growth Hormone Releasing Peptide (GHRP-6, GHRP-2 or Hexarelin) results in synergistic release of GH from pituitary stores. In other words if GHRH contributes a GH amount quantified as the number 2 and GHRPs contributed a GH amount quantified as the number 4 the total GH release is not additive (i.e. 2 + 4 = 6). Rather the whole is greater than the sum of the parts such that 2 + 4 = 10.
While the GHRPs (GHRP-6,GHRP-2 and Hexarelin) come in only one half-life form and are capable of generating a GH pulse that lasts a couple of hours re-administration of a GHRP is required to effect additional pulses.
Growth Hormone Releasing Hormone (GHRH) however is currently available in several forms which vary only by their half-lives. Naturally occurring GHRH is either a 40 or 44 amino acid peptide with the bioactive portion residing in the first 29 amino acids. This shortened peptide identical in behavior and half-life to that of GHRH is called Growth Hormone Releasing Factor and is abbreviated as GRF(1-29).
GRF(1-29) is produced and sold as a drug called Sermorelin. It has a short-half life measured in minutes. If you prefer analogies think of this as a Testosterone Suspension (i.e. unestered).
To increase the stability and half-life of GRF(1-29) four amino acid changes where made to its structure. These changes increase the half-life beyond 30 minutes which is more than sufficient to exert a sustained effect which will maximize a GH pulse. This form is often called tetrasubstituted GRF(1-29) (or modified) and unfortunately & confusingly mislabeled as CJC-1295. If you prefer analogies think of this as a Testosterone Propionate (i.e. short-estered).
Note that some may also refer to this as CJC-1295 without the DAC (Drug Affinity Complex).
Frequent dosing of either the aforementioned modified GRF(1-29) or regular GRF(1-29) is required and as previously indicated works synergistically with a GHRP.
In an attempt to create a more convenient long-lasting GHRH, a compound known as CJC-1295 was created. This compound is identical to the aforementioned modified GRF(1-29) with the addition of the amino acid Lysine which links to a non-peptide molecule known as a "Drug Affinity Complex (DAC)". This complex allows GRF(1-29) to bind to albumin post-injection in plasma and extends its half-life to that of days. If you prefer analogies think of this as a Testosterone Cypionate (i.e. long-estered)
CJC-1295 is difficult to produce and expensive to make. As a result it could be cost-prohibitive to use extensively. Modified GRF(1-29) while less convenient is much less expensive to make and because it is a pure peptide the synthesis process is straightforward. It should sell at a fraction of the cost of CJC-1295.
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A Brief Summary of Dosing and Administration
Dosing GHRPs
The saturation dose in most studies on the GHRPs (GHRP-6, GHRP-2, Ipamorelin & Hexarelin) is defined as either 100mcg or 1mcg/kg.
What that means is that 100mcg will saturate the receptors fully, but if you add another 100mcg to that dose only 50% of that portion will be effective. If you add an additional 100mcg to that dose only about 25% will be effective. Perhaps a final 100mcg might add a little something to GH release but that is it.
So 100mcg is the saturation dose and you could add more up to 300 to 400mcg and get a little more effect.
A 500mcg dose will not be more effective then a 400mcg, perhaps not even more effective then 300mcg.
The additional problems are desensitization & cortisol/prolactin side-effects.
Ipamorelin is about as efficacious as GHRP-6 in causing GH release but even at higher dose (above 100mcg) it does not create prolactin or cortisol.
GHRP-6 at the saturation dose 100mcg does not really increase prolactin & cortisol but may do so slightly at higher doses. This rise is still within the normal range.
GHRP-2 is a little more efficacious then GHRP-6 at causing GH release but at the saturation dose or higher may produce a slight to moderate increase in prolactin & cortisol. This rise is still within the normal range although doses of 200 - 400mcg might make it the high end of the normal range.
Hexarelin is the most efficacious of all of the GHRPs at causing an increase in GH release. However it has the highest potential to also increase cortisol & prolactin. This rise will occur even at the 100mcg saturation dose. This rise will reach the higher levels of what is defined as normal.
Desensitization
GHRP-6 can be used at saturation dose (100mcg) three or four times a day without risk of desensitization.
GHRP-2 probably at saturation dose several times a day will not result in desensitization.
Hexarelin has been shown to bring about desensitization but in a long-term study the pituitary recovered its sensitivity so that there was not long-term loss of sensitivity at saturation dose. However dosing Hexarelin even at 100mcg three times a day will likely lead to some down regulation within 14 days.
If desensitization were to ever occur for any of these GHRPs simply stopping use for several days will remedy this effect.
Chronic use of GHRP-6 at 100mcg dosed several times a day every day will not cause pituitary problems, nor significant prolactin or cortisol problems, nor desensitize.
GHRH
Now Sermorelin, GHRH (1-44) and GRF(1-29) all are basically GHRH and have a short half-life in plasma because of quick cleavage between the 2nd & 3rd amino acid. This is no worry naturally because this hormone is secreted from the hypothalamus and travels a short distance to the underlying anterior pituitary and is not really subject to enzymatic cleavage. The release from the hypothalamus and binding to somatotrophs (pituitary cells) happens quickly.
However when injected into the body it must circulate before finding its way to the pituitary and so within 3 minutes it is already being degraded.
That is why GHRH in the above forms must be dosed high to get an effect.
GHRH analogs
All GHRH analogs swap Alanine at the 2nd position for D-Alanine which makes the peptide resistant to quick cleavage at that position. This means analogs will be more effective when injected at smaller dosing.
The analog tetra or 4 substituted GRF(1-29) sometimes called CJC w/o the DAC or referred to by me as modified GRF(1-29) has other amino acid modifications. They are a glutamine (Gln or Q) at the 8-position, alanine (Ala or A) at the 15-position, and a leucine (Leu or L) at the 27-position.
The alanine at the 8th position enhances bioavailability but the other two amino substitutions are made to enhance the manufacturing process (i.e. create manufacturing stability).
For use in vivo, in humans, the GHRH analog known as CJC w/o the DAC or tetra (4) substituted GRF(1-29) or modified GRF(1-29) is a very effective peptide with a half-life probably 30+ minutes.
That is long enough to be completely effective.
The saturation dose is also defined as 100mcg.
Problem w/ Using any GHRH alone
The problem with using a GHRH even the stronger analogs is that they are only highly effective when somatostatin is low (the GH inhibiting hormone). So if you unluckily administer in a trough (or when a GH pulse is not naturally occurring) you will add very little GH release. If however you luckily administer during a rising wave or GH pulse (somatostatin will not be active at this point) you will add to GH release.
Solution is GHRP + GHRH analog
The solution is simple and highly effective. You administer a GHRH analog with a GHRP. The GHRP creates a pulse of GH. It does this through several mechanisms. One mechanism is the reduction of somatostatin release from the hypothalamus, another is a reduction of somatostatin influence at the pituitary, still another is increased release of GHRH from the brain and finally GHRPs act on the same pituitary cells (somatotrophs) as do GHRHs but use a different mechanism to increase cAMP formation which will further cause GH release from somatotroph stores.
GHRH also has a way of reciprocally reinforcing GHRPs action.
The result is a synergistic GH release.
The GH is not additive it is synergistic. By that I mean:
If GHRH by itself will cause a GH release valued at 2
and GHRP itself will cause a GH release valued at 5
Together the GH is not 7 (5+2) it turns out to say 16!
A solid protocol
A solid protocol would be to use a GHRP + a GHRH analog pre-bed (to support the nightime pulse) and once or twice throughout the day.
For anti-aging, deep restful restorative sleep, the once at night dosing is all you need. For an adult aged 40+ it is enough to restore GH to youthful levels.
However for bodybuilding or fatloss or injury repair multiple dosings can be effective.
The GHRH analog can be used at 100mcg and as high as you want without problems.
The GHRP-6 can always be used at 100mcg w/o problems but a dose of 200mcg will probably be fine as well.
Again desensitization is something to keep an eye on particularly with the highest doses of GHRP-2 and all doses of Hexarelin.
So 100 - 200mcg of GHRP-6 + 100 - 500mcg+ of a GHRH analog taken together will be effective.
This may be dosed several times a day to be highly effective.
A solid approach is a bit more conservative at 100mcg of GHRP-6 + 100mcg of a GHRH analog dosed either once, twice, three or four times a day.
When dosing multiple times a day at least 3 hours should separate the administrations.
The difference is once a day dosing pre-bed will give a youthful restorative amount of GH while multiple dosing and or higher levels will give higher GH & IGF-1 levels when coupled with diet & exercise will lead to muscle gain & fatloss.
Dose w/o food
Administration should ideally be done on either an empty stomach or with only protein in the stomach. Fats & carbs blunt GH release. So administer the peptides and wait about 20 minutes (no more then 30 but no less then 15 minutes) to eat. AT that point the GH pulse has about hit the peak and you can eat what you want.
REP
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Originally Posted by Littleguy
