CJC-1295 + Ipamorelin: understanding the GH-releasing peptide stack

Among the growth hormone (GH) axis peptides studied in preclinical research, the combination of CJC-1295 and Ipamorelin has attracted more consistent attention than perhaps any other pairing in the field. The two compounds target the GH axis through distinct but complementary mechanisms — and their combination produces a more physiologically complete model of GH stimulation than either compound alone.

The GH axis: a brief primer

Growth hormone release from the anterior pituitary is regulated by a push-pull mechanism. Growth hormone-releasing hormone (GHRH) from the hypothalamus stimulates GH release; somatostatin inhibits it. A third input, the ghrelin receptor (GHS-R1a), provides an additional stimulatory pathway independent of GHRH. Endogenous GH is secreted in pulses — typically 5–9 per day in young adults, declining in amplitude and frequency with age.

CJC-1295 operates on the GHRH pathway. Ipamorelin operates on the ghrelin receptor pathway. Together, they target both stimulatory inputs to the somatotroph simultaneously.

CJC-1295: extended GHRH activity

CJC-1295 is a modified version of the first 29 amino acids of GHRH (GHRH 1-29) — the biologically active N-terminal fragment. Native GHRH 1-29 (Sermorelin) has a half-life of approximately 7–10 minutes in circulation, limiting its utility in sustained GH stimulation models. CJC-1295 addresses this through two modifications:

• DAC (Drug Affinity Complex) technology: A maleimidoproprionic acid group that forms a covalent bond with albumin in the bloodstream, extending the half-life of the peptide to approximately 6–8 days (CJC-1295 with DAC).
• Tetrasubstituted amino acid substitutions: Four amino acid modifications that improve protease resistance and maintain GHRH receptor binding affinity.

CJC-1295 without DAC (also called Mod-GRF 1-29) retains the receptor-binding improvements but lacks the albumin-binding group, giving it a half-life of approximately 30 minutes — more suitable for pulsatile GH stimulation protocols.

Ipamorelin: selective GHS-R1a agonism

Ipamorelin is a pentapeptide (Aib-His-D-2Nal-D-Phe-Lys-NH2) that selectively activates the ghrelin receptor (GHS-R1a) to stimulate GH release. It was developed specifically for its selectivity profile — unlike earlier GHRPs (GHRP-2, GHRP-6, Hexarelin), Ipamorelin does not significantly elevate cortisol, ACTH, aldosterone, or prolactin at GH-stimulating doses.

This selectivity is important for research design: studying GH axis effects without simultaneous elevation of stress hormones reduces confounding variables and makes Ipamorelin-generated data cleaner to interpret than data from less selective GHRPs.

Why combine them?

The combination works because the two pathways are synergistic at the level of GH secretion. GHRH stimulates somatotrophs and primes them for GH release; ghrelin receptor activation provides an independent, additive stimulus. When both pathways are active simultaneously, GH pulse amplitude is significantly greater than either stimulus alone — an effect demonstrated consistently in both preclinical models and early human pharmacology studies.

Additionally, CJC-1295's sustained GHRH elevation maintains somatotroph readiness throughout the day, while Ipamorelin's shorter action creates discrete GH pulses. This combination better preserves the pulsatile GH secretion pattern than continuous infusion models, which is important for studies examining downstream IGF-1 dynamics and tissue responses.

Research findings across domains

Body composition and muscle preservation

GH and its downstream mediator IGF-1 promote protein synthesis, lipolysis, and lean mass maintenance. In aged rodent models, CJC-1295/Ipamorelin combination treatment restored GH pulse amplitude toward youthful levels and was associated with reduced fat mass accumulation and preserved lean mass compared to controls. These findings have made the combination a standard research tool in sarcopenia and age-related body composition models.

Bone density

GH and IGF-1 play significant roles in bone metabolism. Preclinical studies using CJC-1295/Ipamorelin combinations have documented increased bone mineral density markers and improved bone microarchitecture in both aged and ovariectomised (osteoporosis model) rodents. This makes it relevant to both ageing research and post-menopausal metabolic models.

Sleep quality

The majority of daily GH secretion occurs during slow-wave sleep, and GH release is mechanistically linked to sleep architecture. Research using GH-releasing peptides in sleep models has documented increased slow-wave sleep duration and improved sleep continuity — effects thought to be secondary to normalised nocturnal GH pulses rather than direct hypnotic action.

Recovery

GH and IGF-1 accelerate protein turnover and tissue repair. In models of exercise-induced muscle damage and tendon stress injury, CJC-1295/Ipamorelin combination treatment was associated with faster functional recovery, reduced markers of persistent muscle damage, and accelerated restoration of contractile strength.

Sex-specific considerations

Women have higher GH pulse frequency but lower pulse amplitude than men at equivalent ages, and higher baseline IGF-1 levels during reproductive years. These differences mean that GH-releasing peptide research produces distinct kinetic profiles by sex. Female subjects treated with CJC-1295/Ipamorelin combinations show increased GH pulse frequency rather than amplitude augmentation, and IGF-1 responses that follow a different temporal pattern than in male subjects. Researchers should use sex-stratified controls and report sex-disaggregated GH and IGF-1 data.

Protocol notes

Standard preclinical protocols use CJC-1295 without DAC (Mod-GRF 1-29) co-administered with Ipamorelin to produce discrete GH pulses, or CJC-1295 with DAC for sustained background GHRH elevation. Dosing intervals of 5 days on / 2 days off are common to preserve feedback sensitivity. Protocols of 12–16 weeks are standard for body composition and bone endpoints; shorter 4–8 week cycles are used for recovery models.

The CJC-1295 and Ipamorelin combination represents a model of rational peptide stack design — each compound addressing a distinct input to the same biological system, producing a combined effect greater than either component alone without mechanistic redundancy.

References

• Teichman, S.L. et al. (2006). Prolonged stimulation of GH and IGF-1 secretion by CJC-1295 in healthy adults. Journal of Clinical Endocrinology & Metabolism, 91(3), 799–805.
• Raun, K. et al. (1998). Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology, 139(5), 552–561.
• Nass, R. et al. (2008). Evidence for acyl-ghrelin modulation of growth hormone release in the fed state. Journal of Clinical Endocrinology & Metabolism, 93(5), 1988–1994.