CJC-1295 — GHRH(1-29) Analogue (no DAC / DAC variants)

Research context only. CJC-1295 (both variants) is an unapproved investigational compound. Nothing on this page constitutes medical advice, and no information here should be used to guide self-administration in humans.

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Discovery and Development

CJC-1295 originated at ConjuChem Inc, a Canadian biotechnology firm, in the early 2000s as part of a programme designed to extend the pharmacological lifespan of endogenous growth hormone-releasing hormone (GHRH). Native GHRH(1-29) — the biologically active amino-terminal fragment of the full forty-four amino acid peptide — degrades rapidly in plasma, with a half-life measured in minutes. ConjuChem's strategy was to attach a drug affinity complex (DAC) — a reactive maleimido-propionic acid moiety — that covalently bonds to circulating albumin after injection, dramatically extending systemic residence time [PMID:15817669].

The compound that reached Phase I clinical evaluation was the DAC-bearing version, formally designated CJC-1295 with DAC or DAC:GRF. Researchers reported mean half-lives of six to eight days and sustained IGF-1 elevation lasting up to fourteen days following a single subcutaneous dose [PMID:16352683]. The compound never advanced beyond Phase II and was never approved in any jurisdiction.

In parallel, the peptide community adopted the underlying GHRH(1-29) backbone — with four strategic amino acid substitutions that confer proteolytic resistance without the albumin-binding DAC — under the label Mod GRF 1-29, sometimes marketed interchangeably as CJC-1295 no DAC. This shorter-acting variant retains a half-life of approximately twenty-five to thirty minutes, pharmacologically resembling sermorelin more closely than the DAC form. The naming overlap between the two variants is a persistent source of confusion in research literature and supplier catalogues alike.

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Mechanism of Action

GHRH Receptor Binding

CJC-1295 (both variants) acts as a selective agonist at the pituitary GHRH receptor (GHRH-R), a seven-transmembrane G-protein-coupled receptor expressed predominantly on somatotroph cells of the anterior pituitary. Binding activates adenylyl cyclase via Gs, elevating intracellular cyclic AMP and triggering a downstream cascade that opens voltage-gated calcium channels. The resulting calcium influx drives exocytosis of stored growth hormone [PMID:2874604].

The four amino acid substitutions in Mod GRF 1-29 — at positions two, eight, fifteen and twenty-seven of the native sequence — protect critical peptide bonds from dipeptidyl peptidase IV (DPP-IV) and other plasma proteases, extending receptor dwell time without fundamentally altering binding geometry or downstream signalling. Receptor occupancy studies confirm that the structural changes preserve full agonist efficacy at the GHRH-R.

Pulse Amplification

Under physiological conditions, GHRH drives discrete, rhythmic GH secretion pulses — typically four to nine per day in healthy adults — interspersed with periods of near-baseline GH. This pulsatile architecture is not merely a pharmacokinetic curiosity; it is functionally important for maintaining hepatic GH receptor sensitivity, downstream IGF-1 generation, and appropriate tissue anabolism [PMID:16984995].

CJC-1295 no-DAC, administered in discrete injections, amplifies each natural GH pulse by saturating GHRH-R at the moment of hypothalamic signal arrival. Because plasma clearance is rapid, receptors return to baseline sensitivity between doses, allowing the next pulse to register normally. The net result is larger GH peaks without erosion of the trough-to-peak ratio that characterises healthy pulsatility [PMID:16849630].

The No-DAC versus DAC Distinction

The DAC variant's albumin-binding mechanism produces a pharmacokinetic profile fundamentally different from its short-acting counterpart. Sustained GHRH-R activation over six to eight days keeps somatotroph cells in a state of continuous stimulation. Clinical data confirm that GH does continue to be released — Ionescu and Frohman demonstrated that pulse secretion persists even under continuous GHRH-R agonism [PMID:16984995] — but the trough concentrations between pulses rise markedly, the pulse amplitude-to-baseline ratio narrows, and the receptor desensitises over time. This blunting of physiological pulse architecture is the primary reason that most contemporary research protocols favour the no-DAC form. The DAC variant's extended convenience comes at the cost of somatotroph dysregulation that short-acting analogues avoid.

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Researched Applications

Published and pre-clinical data point to several domains of investigational interest:

Somatotropic axis augmentation. Phase I and II data demonstrated that single or repeated doses of CJC-1295 (DAC) elevated mean GH concentrations two to ten-fold and IGF-1 levels twenty to sixty percent above baseline in healthy adults aged eighteen to sixty-five [PMID:16352683]. The no-DAC variant is expected to produce qualitatively similar but temporally compressed responses per injection.

Body composition research. Elevated IGF-1 and pulsatile GH are associated in preclinical models with preferential lipolysis in visceral adipose tissue and lean mass preservation during caloric restriction. Combination protocols pairing CJC-1295 no-DAC with a selective GHRP — most commonly ipamorelin — are widely used in pre-clinical in vitro and animal research to study the synergistic effects of simultaneous GHRH-R and ghrelin-receptor co-activation.

Sleep architecture. Deep-sleep stages are the primary window for endogenous GH secretion. Pre-clinical models suggest that amplifying the nocturnal GH pulse with a GHRH analogue may influence slow-wave sleep quantity, though robust human RCT data in this specific application are absent.

Anti-ageing biomarker research. Age-associated decline in GH pulsatility (somatopause) is well characterised [PMID:18046908]. CJC-1295 has been used as a tool peptide in research settings to restore younger-pattern GH profiles in aged rodent models, enabling mechanistic study of downstream metabolic and cellular effects.

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Dosing in Research Protocols

Doses below reflect ranges reported in published studies and non-clinical research settings. They are not clinical recommendations.

No-DAC Variant (Mod GRF 1-29) — Preferred Research Approach

The no-DAC form is administered by subcutaneous injection at 100 µg per dose, three times daily, typically timed to coincide with pre-fasted morning conditions, thirty to forty-five minutes before the main post-workout window, and immediately before sleep. The pre-sleep injection targets the largest physiological GH pulse, which normally occurs shortly after sleep onset.

Research cycle durations typically span eight to twelve weeks. The three-injection cadence preserves pulsatile biology: each injection fires a discrete somatotroph activation event, and the rapid clearance (~30 min half-life) ensures receptor sensitivity is restored before the next dose.

Co-administration with ipamorelin (a selective GHRP with a minimal cortisol/prolactin burden) at 200–300 µg per injection is the most commonly reported combination in pre-clinical research, producing synergistic rather than merely additive GH release.

DAC Variant — Less Common in Current Research

The DAC form is typically dosed at one to two milligrams once weekly by subcutaneous injection, reflecting its six to eight-day effective half-life. Some early protocols used biweekly dosing. Because receptor desensitisation becomes a concern beyond two to four weeks of continuous exposure, research cycles with the DAC variant are generally kept shorter than no-DAC protocols. The DAC variant is not the preferred choice in protocols where pulsatile GH architecture is a variable of interest.

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Safety Observations

Data from Phase I/II trials and pre-clinical models identify the following signal categories:

Water retention and oedema. Elevated GH increases renal tubular sodium reabsorption, producing dose-dependent fluid retention. This is the most consistently reported effect in human trial data [PMID:16352683] and typically resolves after cycle completion.

Injection site reactions. Transient erythema, mild induration and discomfort at the subcutaneous injection site were reported in a minority of trial participants. Proper injection technique and site rotation reduce incidence.

Glucose metabolism. Supraphysiological GH is anti-insulinemic; sustained elevation can impair glucose tolerance. The no-DAC variant's pulsatile pharmacology may limit this risk compared with the continuous elevation profile of the DAC form, though no direct comparison RCT data exist.

Pituitary receptor desensitisation. Extended GHRH-R agonism — particularly with the DAC variant — risks somatotroph downregulation. Cycle breaks of four to eight weeks are standard practice in research designs to allow receptor recovery.

Unknown long-term safety. No long-term human safety data exist for either variant. Extrapolation from animal studies to human clinical risk is not supported by current evidence.

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UK Regulatory Status

CJC-1295 (both variants) is not licensed as a medicinal product in the United Kingdom and has not received a marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA). It is not scheduled under the Misuse of Drugs Act 1971 and is not currently listed as a Psychoactive Substance under the Psychoactive Substances Act 2016.

Supply of CJC-1295 for human administration constitutes supply of an unlicensed medicinal product under the Human Medicines Regulations 2012 and is prohibited without appropriate MHRA authorisation. Possession for personal use is not a criminal offence under existing UK law, but importation for commercial distribution without authorisation carries regulatory and customs risk.

CJC-1295 is distinct from Tesamorelin (Egrifta), a GHRH(1-44) analogue that holds FDA approval in the United States for HIV-associated lipodystrophy. Tesamorelin has no UK or EU marketing authorisation for general use. The two compounds share receptor targets and a broadly similar mechanism but differ in sequence length, pharmacokinetics, and regulatory standing.

Research institutions handling CJC-1295 in a laboratory context should consult current MHRA guidance on unlicensed medicinal products and ensure compliance with local ethics and controlled research frameworks.

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Reconstitution

CJC-1295 is supplied as a lyophilised (freeze-dried) white powder in sealed vials. Standard reconstitution procedure for research use:

Materials required: Bacteriostatic water (0.9% benzyl alcohol preserved); insulin syringes (U-100, 1 mL); alcohol swabs.

Procedure:

• Allow the sealed vial to reach room temperature before opening.
• Wipe the vial rubber septum with an alcohol swab and allow to dry.
• Draw the required volume of bacteriostatic water into the syringe.
• Insert the needle at an angle and allow water to run down the inner vial wall rather than injecting directly onto the lyophilised cake — this minimises peptide degradation from mechanical shear.
• Gently swirl (do not shake or vortex) until the powder dissolves fully to a clear solution.
• Label the vial with the reconstitution date.

Concentration example: Adding two millilitres of bacteriostatic water to a two-milligram vial yields a concentration of one milligram per millilitre (one thousand micrograms per millilitre). A one hundred microgram research dose would require a draw of ten microlitres (0.10 units on a U-100 syringe).

Storage: Reconstituted peptide should be stored refrigerated (two to eight degrees Celsius), protected from light, and used within twenty-eight to thirty days. Discard if the solution becomes cloudy, discoloured, or particulate matter is visible.

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Frequently Asked Questions

What is the difference between CJC-1295 no-DAC and Mod GRF 1-29? They are the same compound. "Mod GRF 1-29" is the systematic name for the four-substitution GHRH(1-29) analogue. "CJC-1295 no DAC" is a common trade/community label. Both designations appear in research literature and supplier documentation.

Why is the no-DAC variant preferred in most research protocols? Because it preserves the pulsatile GH release pattern that is physiologically important for receptor sensitivity and downstream IGF-1 generation. The DAC variant's week-long half-life causes tonic GHRH-R activation, which narrows pulse amplitude and risks somatotroph desensitisation over time [PMID:16984995].

Is CJC-1295 the same as sermorelin? No. Both are GHRH-R agonists but sermorelin is the unmodified GHRH(1-29) sequence with a very short half-life (~ten to twelve minutes), while Mod GRF 1-29 carries four protective substitutions extending its effective half-life to approximately thirty minutes and conferring greater DPP-IV resistance [PMID:18046908].

Can CJC-1295 be combined with ipamorelin? In pre-clinical research, co-administration with ipamorelin — a selective ghrelin-receptor agonist — produces synergistic GH release greater than either compound alone. The combination is among the most studied GHRH + GHRP pairings in the academic literature, though large-scale human RCT data are not available.

How does CJC-1295 compare to Tesamorelin? Tesamorelin is a stabilised GHRH(1-44) analogue with FDA approval for a specific indication (HIV-lipodystrophy). CJC-1295 no-DAC is a shorter GHRH(1-29) analogue with no approved indication anywhere. Tesamorelin has a more extensive human clinical data package; CJC-1295 has been studied in Phase I/II but not progressed to approval. Both require subcutaneous administration; Tesamorelin's approved dose is two milligrams daily.

Is CJC-1295 legal to purchase in the UK? It occupies a regulatory grey area. It is not a controlled drug under the MDA 1971, but supply for human use without MHRA authorisation is not permitted. Legitimate UK research suppliers operate under strict "not for human use" labelling. Purchasers should review current MHRA guidance before ordering.

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Related Stacks

• CJC-1295 + Ipamorelin + Tesamorelin GH Stack — triple somatotropic axis protocol with synergy rationale and timing guidance.
• Ipamorelin + CJC-1295 + BPC-157 Recomp Stack — body-recomposition research protocol combining GH axis stimulation with systemic tissue-repair peptide support.

Source research-grade CJC-1295

CJC-1295 — GHRH(1-29) Analogue (no DAC / DAC variants) is sold for laboratory and in vitro research use only. UK regulatory status: Unapproved research compound in UK, US, EU. Laboratory research use only. Distinct from medicinally-approved Tesamorelin..

Source on PeptideBarn.co.ukFull monograph on PeptideAuthority.co.uk