CJC-1295 with DAC

The peptide is Mod GRF 1-29 with a lysine extension bearing a maleimidopropionyl group, which reacts with the free cysteine-34 thiol on albumin to form a covalent conjugate. That conjugate is protected from renal clearance and dipeptidyl peptidase-4 degradation, giving a terminal half-life of roughly six to eight days. The result is not a pulse but a sustained elevation of basal GH and a two-to-threefold rise in IGF-1 that persists for a week or more after a single dose. Whether that constant bleed is physiologically better or worse than pulsatility is the central unresolved argument about this compound, since GH's anabolic signalling in animals is partly pulse-pattern dependent.

Targets: GHRH receptor (GHRHR), Serum albumin Cys34, Pituitary somatotrophs, IGF-1 axis

• · Most people run 2 mg per week. Doses above about 2 mg per week raise IGF-1 into ranges that are hard to justify outside supervised use.
• · Smoother serum levels and fewer flushing complaints than a single large weekly injection.
• · The published human work used single doses of 30 to 60 mcg/kg and weekly or biweekly 60 mcg/kg, which for an 80 kg adult is roughly 2.4 to 4.8 mg. Real-world dosing is deliberately more conservative.

Work out your exact syringe units →

• very commonWater retention, puffy hands and face— The most reliable complaint about the DAC version; it is the sustained IGF-1 elevation showing up.
• commonJoint aching and stiffness— Classic GH-excess symptom. Reduce the weekly dose.
• commonCarpal tunnel symptoms— Numb or tingling hands on waking; a clear signal to back off.
• commonFlushing and warmth after injection— GHRH analogues are vasoactive; usually settles within 20 minutes.
• commonInjection-site reactions— Redness and a small lump can persist for a day or two.
• uncommonReduced insulin sensitivity and higher fasting glucose— More likely here than with pulsatile GHRPs because GH exposure is continuous.
• uncommonHeadache

• Active malignancy or a recent cancer history - sustained IGF-1 elevation is exactly the wrong signal.
• Active proliferative diabetic retinopathy.
• Poorly controlled diabetes or significant insulin resistance.
• Known pituitary tumour, including any untreated adenoma.
• Pregnancy and breastfeeding.

• synergyipamorelin — The stack is standard, though the sustained GHRH signal blunts some of the pulsatile advantage a GHRP would otherwise provide.
• redundantsomatropin — Both raise IGF-1; combining them stacks the same side effects with no clear additional benefit.
• cautioninsulin — GH raises insulin requirements, so diabetics on insulin may need dose adjustment.
• redundantcjc-1295-no-dac — Same receptor, same peptide backbone. Pick one.

• · IGF-1 at baseline and again at four and twelve weeks; the goal is the upper half of the age-adjusted range, not above it.
• · Fasting glucose and HbA1c every eight to twelve weeks.
• · Watch for morning hand numbness and increasing ring size as early GH-excess signals.

Never approved anywhere; development was abandoned. Sold as a research chemical and prohibited in sport under WADA S2.

• Teichman et al. 2006 JCEM, prolonged stimulation of GH and IGF-1 by CJC-1295 in healthy adults (trial)
• ConjuChem drug affinity complex albumin-conjugation platform description (other)

The GHRH receptor is Gs-coupled, so the signalling arm here is entirely different from a GHRP: adenylate cyclase, cyclic AMP, protein kinase A, CREB phosphorylation. That drives both immediate exocytosis of stored GH and transcription of the GH1 gene, meaning a GHRH analogue refills the granule pool as well as emptying it. This is why GHRH analogues do not desensitise the way GHS-R1a agonists do - they are supporting the somatotroph rather than exhausting it. The DAC modification changes the pharmacology qualitatively, not just quantitatively. Native GHRH signalling is pulsatile because the hypothalamus releases it in bursts, and the somatotroph experiences alternating GHRH and somatostatin waves. A covalently albumin-bound analogue with a six to eight day half-life abolishes that pattern and delivers a continuous GHRH signal. In animals, GH's effects on hepatic gene expression are partly pattern-dependent - a continuous GH signal produces a different STAT5b activation profile than a pulsatile one, with different downstream transcription, and the male-pattern pulsatile profile is what drives some of the anabolic gene set. Whether that translates to humans at these doses is genuinely unresolved and is the single most important open question about this compound. What is not in doubt is the IGF-1 curve: Teichman's healthy adults sustained a two- to threefold IGF-1 elevation, and with repeated dosing IGF-1 remained elevated for up to 28 days. That is where the accumulation comes from, and it is why the fourth weekly dose does more than the first.

The dominant failure mode is dosing a DAC product on a no-DAC schedule. Someone buys a vial labelled 'CJC-1295' without checking whether it contains the drug affinity complex, injects 100 mcg nightly on the assumption that it clears in half an hour, and by week two is carrying a week's worth of stacked doses with an IGF-1 they have not measured. Puffy face, aching joints, numb hands on waking, and a fasting glucose that has quietly moved. The second failure is impatience with the washout: the last dose is still pharmacologically active for well over a week, so a 'four-week break' is really a two-and-a-half-week break, and pre-competition or pre-bloodwork timing calculations that ignore this go wrong. Third, this is the compound where reconstitution damage matters most. The maleimide group is the reactive part of the molecule and it hydrolyses; a vial that spent five days in a hot mailbox may have lost the very chemistry that makes it long-acting, leaving you with an expensive short-acting GHRH analogue that you are dosing weekly. Fourth, people treat carpal tunnel symptoms and joint aching as a sign it is working. They are a sign the dose is too high, and on a six-day half-life you cannot fix that quickly.

1. 1 mgWeeks 1 to 2 — 1 mg once weekly. This is deliberately below the common 2 mg because the water retention, joint aching and carpal tunnel symptoms that make people quit almost all appear in the first fortnight, and because a six-to-eight-day half-life means a dose you regret is a dose you live with for a week.
2. 1.5 mgWeeks 3 to 4 — 1.5 mg weekly, or 750 mcg twice weekly if flushing after the single injection was unpleasant. Splitting the dose smooths peaks without changing total exposure.
3. 2 mgWeek 5 onward — 2 mg weekly, the standard maintenance dose. Check IGF-1 at week 4 before stepping here and again at week 12. If IGF-1 is already at the top of the age-adjusted range at 1.5 mg, stay there.
4. —Not recommended — There is no fourth step. The published human doses of 30 to 60 mcg/kg - roughly 2.4 to 4.8 mg for an 80 kg adult - drove IGF-1 well outside the normal range for weeks at a time. Going above 2 mg weekly outside supervision buys side effects and an IGF-1 number you would not want on a chart.

• GHRH receptor (GHRHR), pituitary somatotroph — Not published as a Kd for the DAC conjugate. The unconjugated tetrasubstituted backbone is more potent than native GHRH(1-29); the albumin conjugate trades some receptor affinity for enormously longer exposure.

  Gs coupling, adenylate cyclase activation, cAMP rise, PKA and CREB signalling. Both immediate GH release and increased GH1 transcription, so the releasable pool is replenished rather than depleted.

• Serum albumin cysteine-34 — Covalent thioether bond formed by Michael addition of the free Cys34 thiol to the maleimide

  Not a pharmacological target but the entire delivery mechanism. Cys34 is the only free thiol on human albumin, which is what makes the chemistry site-specific.

• Hepatic IGF-1 production (indirect, via GH receptor and STAT5b) — Not applicable

  Sustained two- to threefold IGF-1 elevation. This is the pharmacodynamic endpoint that was actually measured in humans and it is the one to monitor.

• Teichman et al., single and multiple ascending dose study of CJC-1295 in healthy adults 1/2 · 2006

  Dose-dependent 2- to 10-fold increase in mean plasma GH sustained for six days or more after a single subcutaneous injection, with IGF-1 elevated 1.5- to 3-fold for nine to eleven days. Estimated half-life 5.8 to 8.1 days. With multiple doses, IGF-1 remained elevated for up to 28 days. This single study is the entire human evidence base for CJC-1295 with DAC.

• Jetté et al., preclinical identification of CJC-1295 as a long-lasting GRF analogue via albumin bioconjugation preclinical · 2005

  Demonstrated that hGRF(1-29)-albumin bioconjugates activate the GRF receptor on the rat anterior pituitary and identified CJC-1295 as the lead long-acting analogue. This is the paper that established the drug affinity complex mechanism.

GH rises within hours of the first injection and stays elevated for six days or more. IGF-1 climbs over the first three to five days and peaks somewhere in the first week after a single dose. With weekly dosing, IGF-1 continues climbing dose-on-dose and reaches a genuine plateau at around three to four weeks - which is why a week-4 IGF-1 draw is the meaningful one and a week-1 draw underestimates where you will end up. Water retention typically appears in days three to ten of the first week and is worst in the first fortnight. Joint aching, when it happens, is a week-two-to-four phenomenon. Any body-composition change is a two-to-three-month timeline. After the final dose, expect meaningful drug exposure for another ten to fourteen days and IGF-1 to take three to four weeks to return to baseline.

The standard pairing with ipamorelin is worth thinking about rather than assuming. The reason GHRH plus GHRP is synergistic is that the GHRP removes somatostatin tone at the moment the GHRH signal arrives - a timing effect. With the DAC version the GHRH signal is always present, so the GHRP is no longer synchronising anything; it is simply adding its own somatostatin suppression on top of a constant background. The combination still produces more GH than either alone, but the elegant part of the synergy is gone, and you are stacking two independent sources of IGF-1 elevation with the fluid retention and glucose cost that implies. If you want the classic synergy, use the no-DAC version. Combining with exogenous somatropin or with somapacitan is straightforwardly redundant - same downstream axis, doubled side effects. Combining with insulin or any oral hypoglycaemic in a diabetic requires active dose management, not a note in a table: continuous GH exposure will raise insulin requirements over days to weeks. Tesamorelin plus CJC-1295 DAC is two GHRH-receptor agonists at once; pick the one with the phase 3 data.

Against CJC-1295 without DAC: this is a genuinely different drug despite the shared name and near-identical backbone. The DAC version gives sustained, measurable, accumulating IGF-1 elevation with one or two injections a week and a fluid-retention profile to match. The no-DAC version gives a sharp pulse, minimal accumulation and far fewer complaints, but requires daily injections and gives you nothing you can easily measure. Against tesamorelin: tesamorelin is the same receptor with two phase 3 trials, an FDA approval and a documented visceral-fat effect, but it is daily and pulsatile. If you want GHRH-receptor agonism with actual evidence, that is where it lives. Against somatropin: somatropin is more powerful, more predictable and more dangerous, and it suppresses your own axis; CJC-1295 DAC works through your pituitary and therefore retains some feedback protection - but at 2 mg weekly it is producing IGF-1 elevations comparable to low-dose GH with none of the manufacturing quality control. Against MK-677: different receptor, similar sustained-exposure philosophy, similar glucose penalty, and MK-677 has vastly more human data.

$90–$220/month. Approximate grey-market pricing. A 2 mg vial commonly runs 25 to 55 USD, and at 2 mg weekly that is roughly four vials a month. Verify from a third-party certificate of analysis whether you have the DAC version - vendors mislabel this constantly, and the price difference between DAC and no-DAC does not reliably tell you which is which. Prices are observed, approximate and volatile.

• ?Whether continuous GHRH exposure is better or worse than pulsatile exposure for human body composition is unresolved. The pattern-dependence of GH signalling is real in rodents; its magnitude in humans at these doses is not known.
• ?No published volume of distribution, clearance value or absolute bioavailability for the albumin conjugate.
• ?Protein binding is effectively 100 percent by design since the drug is covalently attached to albumin, but no formal binding study was located, so the field is left null rather than asserted.
• ?The 28-day time to steady state given here is inferred from the observation that IGF-1 remained elevated up to 28 days with repeated dosing. It is not a formally reported Tss.
• ?The exact structure of the C-terminal lysine-maleimidopropionyl extension is described consistently across secondary sources but was not resolved from a primary structural reference in this session, so the sequence is flagged unverified. The molecular weight of 3647.2 in the Core record was likewise not independently confirmed.
• ?There is no human safety data beyond the single ConjuChem phase 1/2 programme, and no data at all on runs longer than a few months.
• ?Grey-market product identity is a serious and unquantified risk here. There is no way to distinguish DAC from no-DAC product by appearance, and the pharmacological consequence of getting it wrong is a tenfold dosing error.

• 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 Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA, Journal of Clinical Endocrinology and Metabolism, 2006 · PMID 16352683

  The only substantial human study. Source of the 5.8 to 8.1 day half-life, the 2- to 10-fold GH elevation, the 1.5- to 3-fold IGF-1 elevation and the 28-day IGF-1 persistence with repeat dosing.

• 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 Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP, Endocrinology, 2005 · PMID 15817669

  The chemistry and preclinical validation of the drug affinity complex. Establishes that the albumin conjugate retains GRF receptor activity.

• Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men Soule S, King JA, Millar RP, Journal of Clinical Endocrinology and Metabolism, 1994 · PMID 7962295

  Direct human evidence for why the position-2 D-alanine substitution is in this molecule at all: it blocks DPP-4 cleavage, lengthening half-life and reducing metabolic clearance.

• Polyethylene glycol-conjugated growth hormone-releasing hormone is long acting and stimulates GH in healthy young and elderly subjects Munafo A, Nguyen TX, Papasouliotis O, Lécuelle H, Priestley A, Thorner MO, European Journal of Endocrinology, 2005 · PMID 16061831

  Further reading rather than direct evidence: an independent demonstration that half-life extension of a GHRH analogue produces sustained GH stimulation in humans, which supports the general approach.