CJC-1295 No DAC

CJC-1295 No DAC is a synthetic GHRH analogue — tetrasubstituted GRF (1-29), commonly sold as Mod GRF (1-29) — lacking the Drug Affinity Complex maleimide linker that binds the DAC variant to serum albumin.

Only residues 1-29 of the 44-amino-acid GHRH molecule are required for receptor activation. Substitutions at positions 2, 8, 15 and 27 confer stability: position 2 blocks DPP-4 cleavage, positions 8 and 27 prevent deamidation and oxidation, and position 15 enhances bioactivity. Native GHRH has a half-life of roughly 2 minutes; the modified peptide extends this to approximately 30 minutes, against the DAC variant's 6 to 8 days.

The consequence is discrete pulsatile GH release from pituitary somatotrophs that tracks the physiological secretion pattern, rather than the sustained trough elevation produced by albumin-bound CJC-1295. That pulsatility is what avoids the somatotroph adaptation associated with continuous exposure, and it is why most experienced users favour the No DAC version, reserving the DAC variant for convenience.

Downstream, hepatic conversion elevates IGF-1 and LR3 IGF-1 as the effector arm for hypertrophy and regeneration. Because the axis is stimulated rather than bypassed, somatostatin-mediated negative feedback remains intact and endogenous production is not suppressed as it is with exogenous hGH. Reported GH elevation with this version is 200–1000% above baseline.

Both variants were developed by ConjuChem Biotechnologies. CJC-1295 with DAC reached Phase 2 trials for HIV-related lipodystrophy and growth hormone deficiency before development was halted; neither version is FDA approved. No published human clinical trials exist for CJC-1295 without DAC — its use rests on the shared mechanism with the DAC version and the broader pharmacology of GHRH analogues.

It is the standard GHRH-side choice for pairing with a ghrelin agonist, and the preferred variant for longer-term use and bioidentical GH optimisation.

Two afferent signals govern somatotroph output. Hypothalamic GHRH drives synthesis and secretion via the GHRH receptor; ghrelin acts at GHS-R1a to release stored GH and simultaneously suppress somatostatin. Co-activation is synergistic, which is why the dominant endogenous pulse occurs in slow-wave sleep when insulin is low, ghrelin high and GHRH tone active.

CJC-1295 No DAC occupies the GHRH receptor on somatotrophs, initiating a G protein, cyclic AMP and protein kinase cascade that drives GH synthesis and release. It addresses only the GHRH limb: it expands production capacity without emptying the releasable pool or lifting somatostatin inhibition. Combined GHRH plus GHRP administration in animal models produces peak GH 2 to 5 fold higher than the sum of individual effects, which is the rationale for pairing with Ipamorelin — established by Raun et al. (1998) as the first selective secretagogue, without cortisol, ACTH or prolactin elevation even at 200-fold the effective dose.

Hepatic conversion to IGF-1 supplies the downstream anabolic signal via receptor binding and mTOR activation. Rising IGF-1 triggers hypothalamic somatostatin release, closing the negative feedback loop. Because the compound acts upstream of that loop, pituitary control and endogenous output are preserved, unlike exogenous hGH, which produces feedback suppression and dependency, or direct IGF-1, which adds receptor desensitisation.

Exogenous GH and secretagogues are not additive: somatostatin elevation after a single GH injection inhibited the GHRH pathway by approximately 86 percent and the ghrelin pathway by approximately 32 percent.

Kinetics define the phenotype. DPP-4 resistance extends the ~2 minute native half-life to ~30 minutes, producing a rise, peak and return to baseline. Ionescu and Frohman (2006) showed that with the DAC variant pulsatility persisted under continuous stimulation, but trough GH rose 7.5 fold, with overall GH up 46 percent and IGF-1 up 45 percent — sustained trough elevation rather than sharp peaks and deep valleys.

Insulin binds somatotrophs directly and suppresses release, so postprandial dosing blunts the pulse a 30-minute compound cannot wait out.

The compound acts through three described axes: GHRH receptor activation driving pulsatile pituitary GH release; hepatic conversion to IGF-1 and LR3 IGF-1 as the effector arm for hypertrophy and regeneration; and short-acting kinetics engineered for rapid absorption and clearance to preserve pulsatility.

Sleep architecture: GHRH independently increases duration and intensity of slow-wave sleep, reinforcing the endogenous nocturnal pulse rather than overriding it, and improving circadian regulation.

Body composition and structure: IGF-1 receptor binding activates mTOR and muscle protein synthesis, improving recovery and reducing soreness; GH activates hormone-sensitive lipase, driving lipolysis with a particular effect on visceral adipose tissue; collagen synthesis proceeds across skin, joints and connective tissue with accelerated tendon and ligament repair; bone mineral density improves with sustained use, relevant to age-related decline.

Metabolic and cardiovascular: reduced triglycerides and cardiovascular support via improved body composition. Growth hormone also alters insulin sensitivity, which is why glucose monitoring belongs alongside use.

Regenerative and immune: increased B- and T-cell counts in ageing and immunocompromised subjects, increased antibody production, support for stem cell regeneration after organ or tissue damage, stimulation of pancreatic cell proliferation, reported cardiac tissue repair after myocardial infarction, enhanced fertility and libido particularly in older adults, and documented cognitive support after neurological injury.

Prerequisite signalling: androgen receptor blockade shuts down the downstream IGF-1 cascade, and testosterone directly upregulates intramuscular IGF-1 expression. In women, oestrogen gates the anabolic response — postmenopausal subjects without replacement do not mount the expected muscle protein synthesis response to exercise, and restoration returns it. Amplifying a signal the tissue cannot receive is wasted expenditure.

Alba et al. (2006) additionally reported increased total pituitary RNA and GH mRNA in GHRH knockout mice, suggesting somatotroph proliferation under once-daily administration.

Expect a slow accrual rather than an acute effect, and set expectations accordingly — the most recurring complaint in user reports is anticipating faster or more dramatic results than the class delivers.

Weeks 1 to 2: improved sleep onset and depth, vivid dreams, better morning recovery. This is the most consistently reported effect across platforms and the earliest subjective marker, driven by GHRH's direct action on slow-wave sleep.

Weeks 2 to 4: reduced DOMS, better session-to-session recovery, occasional early skin quality changes.

Weeks 4 to 8: body composition begins to move where nutrition and training are controlled; improved intra-session fullness; early joint comfort.

Weeks 8 to 12: lipolytic effect becomes visible, weighted toward visceral fat and lean-mass sparing, and slower than caloric restriction or GLP-1 receptor agonism.

Months 3 to 6: connective tissue and dermal remodelling — skin quality, joint health, tendon and ligament resilience.

In practice, 16 to 24 week runs return sleep quality and fat-loss efficiency as the dominant outcomes, with fat loss frequently unrecognised until late in the cycle. Hypertrophy and strength returns are often negligible in already TRT-optimised subjects.

User reports on combination protocols describe improved recovery, reduced soreness and gradual body composition change over 8 to 16 week runs. One forum report described 100 mcg of Mod GRF (1-29) with 100 mcg Ipamorelin three times daily raising IGF-1 from 227 ng/mL to 406 ng/mL. Anecdote, not trial data, but consistent with mechanism.

Objective confirmation: baseline IGF-1 and a repeat at 4 to 8 weeks. Acute effects reported more often with the No DAC version than with the DAC variant include post-injection flush, warmth and transient heart rate elevation.

Half-life is approximately 30 minutes, so adverse effects resolve rapidly and titration is responsive. For reference, the DAC variant's half-life is 5.8 to 8.1 days (Teichman et al., 2006).

No published dose-finding studies exist for the subcutaneous protocols used in practice for CJC-1295 without DAC. The available clinical data used CJC-1295 with DAC dosed in mcg per kg. The protocols below reflect clinical practice patterns, not published evidence.

Reconstitution: 5 mg vial with 2 mL bacteriostatic water, giving 250 mcg per 10 units on an insulin syringe. Refrigerate and use within 28 days. A 10 mg vial reconstituted with 2.5 mL yields 4 mg/mL. Use 0.3 mL/cc (30 unit) or 0.5 mL/cc (50 unit) syringes for accuracy at these volumes.

Standard: 100 to 300 mcg per subcutaneous injection, once daily, fasted, at least 2 hours after eating, with no food for at least 30 minutes post-injection. Some protocols run 2 to 3 times daily; with a ~30 minute half-life each administration constitutes one discrete pulse, so frequency, not per-dose amount, sets total pulse count.

The fasting requirement is mechanistically load-bearing. Insulin binds somatotrophs directly and suppresses GH release — injecting into a postprandial insulin peak is accelerator and brake simultaneously.

Goal-dependent timing: pre-bed fasted dosing for fat loss, exploiting overnight GH exposure; morning dosing 30 minutes before the first meal for hypertrophy, since postprandial insulin supports hepatic IGF-1 conversion; night-time dosing for general optimisation, amplifying the endogenous nocturnal pulse.

Combination dosing is near-universal: CJC-1295 No DAC with Ipamorelin at 1:1 in the same injection, commonly 100 mcg of each nightly fasted, titrated to 200 to 300 mcg of each against response and IGF-1 levels.

Duration: 12 to 16 weeks continuous, then 4 weeks off. The 5-on/2-off convention lacks support — acute desensitisation resolves in roughly 60 minutes, chronic desensitisation develops over approximately 16 weeks and reverses with approximately 4 weeks off. Tesamorelin trials that secured FDA approval used daily dosing for 26 weeks, and a two-year MK-677 study used continuous daily dosing with GH and IGF-1 remaining elevated throughout.

For context, CJC-1295 with DAC is dosed 1 to 2 mg per week, once or twice weekly, for 8 to 12 weeks, without strict timing requirements.

No published human clinical trials exist for CJC-1295 without DAC (Mod GRF 1-29); its use rests on the shared mechanism with the DAC variant and on general GHRH analogue pharmacology.

Teichman et al. (2006), Journal of Clinical Endocrinology and Metabolism: two randomised, placebo-controlled, double-blind trials of CJC-1295 with DAC in healthy adults aged 21 to 61 — a single ascending dose trial over 28 days and a multiple dose trial with weekly or biweekly injection over 49 days. A single injection raised GH 2 to 10 fold for 6 or more days and IGF-1 1.5 to 3 fold for 9 to 11 days; half-life was estimated at 5.8 to 8.1 days. Multiple dosing kept IGF-1 above baseline for up to 28 days with evidence of cumulative effect. Well tolerated at 30 or 60 mcg per kg with no serious adverse reactions. Limitations: DAC variant only, small samples, no safety data beyond 49 days.

Ionescu and Frohman (2006), same journal: continuous GHRH stimulation preserved pulsatility. Trough GH rose 7.5 fold with pulse frequency and magnitude unchanged; overall GH rose 46 per cent and IGF-1 45 per cent, the authors attributing the IGF-1 rise primarily to elevated troughs.

Alba et al. (2006), Am J Physiol Endocrinol Metab: in GHRH knockout mice, once-daily CJC-1295 normalised body weight and length, whereas 48- and 72-hour intervals improved but did not normalise growth. Total pituitary RNA and GH mRNA increased, suggesting somatotroph proliferation. Genetically modified model, limited translation.

Jette et al. (2005), Endocrinology: characterised the albumin-binding hGRF 1-29 bioconjugate, with a 4-fold increase in GH area under the curve over 2 hours versus standard GRF 1-29 in rats and plasma detection beyond 72 hours.

Raun et al. (1998), Eur J Endocrinol: Ipamorelin as the first selective secretagogue, no significant cortisol, ACTH, or prolactin elevation even at 200-fold the effective dose — the basis for the standard pairing over GHRP-6 and GHRP-2.

Rahim and Shalet (1998), Growth Horm IGF Res: 16 weeks of twice-daily hexarelin in 12 healthy elderly subjects; GH response declined significantly at weeks 4 and 16 and recovered to baseline 4 weeks after cessation — the desensitisation timeline used for cycling decisions.

Phase 2 development in HIV-related lipodystrophy enrolled 192 participants and was halted in July 2006 after a participant died hours after an eleventh injection; the attending physician concluded undiagnosed coronary artery disease with plaque rupture, unrelated to the peptide. Development was not resumed, and neither version is FDA approved.