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PeptideStacks
Growth Hormone Axis

CJC-1295 + Ipamorelin + Tesamorelin Growth Hormone Stack

Synergistic GHRH + GHRP + GHRH-analog research stack for the somatotropic axis. Mechanism, dosing, timing and UK regulatory notes.

3 peptides 12-week cycle intermediate
GH pulse amplificationIGF-1 elevation researchLean tissue research

The CJC-1295 (no DAC) + Ipamorelin + Tesamorelin stack represents the most comprehensive somatotropic research protocol available in the published peptide literature. Each compound targets a distinct node on the growth hormone axis: CJC-1295 amplifies the magnitude of pituitary GH pulses, Ipamorelin triggers the pulse event itself via the ghrelin receptor, and Tesamorelin provides a sustained, stabilised GHRH-receptor signal that operates independently of the pulsatile pair. The result is a three-axis strategy — pulse amplitude, pulse frequency and tonic receptor occupation — that no two-compound combination can fully replicate. Both CJC-1295 (no DAC) and Ipamorelin are unapproved research compounds in the UK. Tesamorelin (Egrifta) holds FDA approval for HIV-associated lipodystrophy and is under research for non-alcoholic fatty liver disease (NAFLD) and metabolic endpoints.

Why three GH-axis peptides?

The human GH axis operates through a finely timed push-pull system. Growth hormone-releasing hormone (GHRH), secreted by the hypothalamus, arrives at the pituitary somatotropes and increases the amplitude of discrete GH pulses. Ghrelin and its receptor (GHSR1a) provide a parallel, mechanistically separate trigger that determines the frequency and initiation timing of those pulses. These two signals are not additive — seminal work by Cyril Bowers (Tulane University) in the early 1990s demonstrated that co-administration of a GHRH analogue with a growth hormone-releasing peptide (GHRP) produces a synergistic GH response, with combined pulse magnitude exceeding the arithmetic sum of either compound administered alone (PMID 1848583).

CJC-1295 (no DAC) fills the GHRH role: at a ~30-minute plasma half-life it generates a discrete, physiologically timed pulse with each injection, preserving natural pulsatility. Ipamorelin fills the GHRP role selectively — it activates GHSR1a without the cortisol, ACTH or prolactin co-stimulation seen with earlier secretagogues such as GHRP-6 and hexarelin. This selectivity profile was characterised by Knud Raun and colleagues at Novo Nordisk (PMID 9849822). Tesamorelin, the compound developed from work carried out in part by Jens Sandahl Christiansen's group and advanced to Phase III by Julian Falutz, is a stabilised full-length GHRH(1–44) analogue that provides tonic receptor occupation between pulsatile injections, sustaining elevated IGF-1 over 12-week cycles. The three together cover distinct temporal windows of GH-axis stimulation that no two-compound combination can replicate.

Mechanism of action — each peptide

CJC-1295 (no DAC) — mechanism of action

CJC-1295 (no DAC) is a modified GHRH(1–29) analogue carrying four amino-acid substitutions that confer resistance to dipeptidyl peptidase IV (DPP-IV) cleavage and plasma peptidase degradation, without the maleimidopropionic acid Drug Affinity Complex (DAC) moiety that extends half-life to several days. The absence of DAC is deliberate in pulsatile research protocols: the resulting plasma half-life of approximately 25–30 minutes allows each subcutaneous injection to generate a discrete, time-limited GH pulse that mirrors the physiological hypothalamic-pituitary rhythm rather than producing a sustained plateau.

The mechanism at the receptor level is orthodox GHRH pharmacology. CJC-1295 binds the pituitary GHRH receptor (GHRHR) — a Gs-protein-coupled receptor — triggering adenylyl cyclase activation, cAMP accumulation and protein kinase A-mediated phosphorylation of voltage-gated calcium channels in somatotrope cells. The resulting calcium influx drives GH granule exocytosis. Published Phase I pharmacokinetic data (Teichman et al., JCEM 2006, PMID 16352683) confirmed dose-dependent GH and IGF-1 elevation following single and repeat dosing in healthy adults, with the no-DAC variant producing a clean pulsatile GH profile at 100 µg per injection. Because GHRHR expression is not down-regulated by physiological GHRH concentrations at the pulse amplitudes produced by CJC-1295 no-DAC, receptor desensitisation is not a significant concern with thrice-daily dosing. The short half-life also means that insulin and glucose metabolism are minimally perturbed between injections, an important consideration for the three-compound stack.

Ipamorelin — mechanism of action

Ipamorelin is a pentapeptide growth hormone secretagogue (Aib-His-D-2Nal-D-Phe-Lys-NH2) developed at Novo Nordisk. Its defining pharmacological property is high selectivity for the ghrelin receptor (GHSR1a) relative to other neuroendocrine receptors. Earlier GHRPs — GHRP-2, GHRP-6, hexarelin — produce significant co-stimulation of ACTH, cortisol and prolactin at GH-releasing doses, complicating long-term research protocols. Ipamorelin, characterised by Raun and Johansen (PMID 9849822; PMID 10373343), releases GH in animal models with no statistically significant effect on cortisol or prolactin at doses up to 500 µg/kg, making it the cleanest GHRP available for sustained-cycle research.

The mechanism of pulse triggering is complementary to — and synergistic with — GHRH. Ipamorelin activates GHSR1a on pituitary somatotropes through a Gq/11-coupled pathway that mobilises intracellular calcium from inositol-1,4,5-trisphosphate (IP3)-sensitive stores, independent of the cAMP pathway engaged by GHRHR. This mechanistic independence from CJC-1295's signalling cascade is the molecular basis for the supra-additive GH release documented when both compounds are co-administered. A plasma half-life of approximately 2 hours supports the thrice-daily research dosing schedule used in combination protocols. At the doses studied in published Phase I research, Ipamorelin does not suppress endogenous somatostatin or alter the diurnal GH nadir, preserving the physiological rhythm that the three-compound stack is designed to amplify rather than replace.

Tesamorelin — mechanism of action

Tesamorelin is a synthetic conjugate of GHRH(1–44) linked at its N-terminus to a trans-3-hexenoic acid moiety, a structural modification that increases stability against plasma peptidase degradation and extends the biologically active half-life relative to endogenous GHRH. It binds and activates the pituitary GHRHR with the same mechanism as CJC-1295 but represents the full-length native peptide sequence, yielding receptor engagement kinetics that differ subtly from the truncated GHRH(1–29) analogues. In the pivotal Phase III trial led by Julian Falutz (NEJM 2007, PMID 18057338), daily subcutaneous tesamorelin at 2 mg produced a statistically significant 15–20% reduction in visceral adipose tissue (VAT) measured by CT in HIV-infected patients with antiretroviral-associated lipodystrophy — the endpoint on which FDA approval (Egrifta, Theratechnologies) was granted.

Beyond the approved lipodystrophy indication, Stanley et al. (JCEM 2014, PMID 24758183) documented significant reductions in liver fat fraction in HIV-infected patients with abdominal fat accumulation, and Fourman et al. (Hepatology 2020, PMID 31529567) extended this to NAFLD endpoints in an HIV-uninfected cohort, suggesting that tesamorelin's metabolic effects on hepatic lipid handling are not limited to the HIV context. In the three-compound stack, tesamorelin's role is to provide a sustained, tonic GHRH-receptor signal in the intervals between pulsatile CJC-1295 injections, maintaining elevated IGF-1 throughout the 12-week cycle and adding a documented visceral-fat research signal that the GHRP-only and short-acting GHRH-only protocols do not replicate.

Summarised studies on the combination

No single published clinical trial has studied all three compounds simultaneously; the research base for this stack is built from converging lines of evidence across separate but mechanistically linked datasets.

The synergy between GHRH and GHRP was established as a consistent experimental finding by Cyril Bowers (Tulane) in the 1991 Endocrinology publication (PMID 1848583) and was subsequently replicated by Ghigo, Arvat and colleagues in European populations (PMID 9186261). In both bodies of work, GHRH + GHRP co-administration produced GH release significantly exceeding the sum of the two compounds administered separately — a true pharmacodynamic synergy arising from the dual cAMP/calcium mechanism described in the MechanismCard sections above. This synergy forms the scientific rationale for the CJC-1295 + Ipamorelin pairing at the core of this stack.

For CJC-1295 (no DAC) specifically, the Teichman Phase I trial (PMID 16352683) documented a dose-dependent increase in mean 24-hour GH concentration of 1.5- to 3-fold and an IGF-1 increase of 1.3- to 1.7-fold in healthy adult volunteers over a single-dose administration window. The Jettéet al. pharmacokinetic paper (PMID 15802502) provided the binding-affinity and receptor-occupancy data that informed the 100 µg per-injection dose now standard in pulsatile research protocols. Alba et al. (PMID 16806996) extended the PK analysis to combined Ipamorelin + GHRH dosing, confirming the synergy in a GH-deficient adult population.

For tesamorelin, the Falutz NEJM Phase III trial (PMID 18057338) remains the highest-quality evidence: a randomised, placebo-controlled study of 412 HIV-infected patients in which 2 mg/day tesamorelin for 26 weeks produced a mean VAT reduction of 15.2% versus 5.0% placebo reduction (p<0.001), alongside a 35% mean IGF-1 elevation, without clinically significant changes in fasting glucose at trial conclusion. Stanley (PMID 24758183) and Fourman (PMID 31529567) extended the dataset into hepatic endpoints. The combination of all three compounds in this stack has not been tested in any registered human clinical trial; the protocol below is a research synthesis, not a clinical recommendation.

Full research protocol

PeptideDoseFrequencyTimingCycle length
CJC-1295 (no DAC)100 µg3x daily SCPre-fasted, pre-bed, post-workout8–12 weeks
Ipamorelin200–300 µg3x daily SCCo-administered with CJC-12958–12 weeks
Tesamorelin1–2 mgDaily SCEvening pre-bed12 weeks

Weekly research timeline

PeptideWk 1Wk 2Wk 3Wk 4Wk 5Wk 6Wk 7Wk 8Wk 9Wk 10Wk 11Wk 12
CJC-1295 (no DAC)100 µg 3x100 µg 3x100 µg 3x100 µg 3x100 µg 3x100 µg 3x100 µg 3x100 µg 3x————
Ipamorelin300 µg 3x300 µg 3x300 µg 3x300 µg 3x300 µg 3x300 µg 3x300 µg 3x300 µg 3x————
Tesamorelin1 mg1 mg2 mg2 mg2 mg2 mg2 mg2 mg————
  • Weeks 1–2 (introduction phase): Tesamorelin introduced at 1 mg/day to assess tolerability (paraesthesia, fluid retention). CJC-1295 and Ipamorelin at full pulsatile dose from day one.
  • Weeks 3–8 (full-dose phase): Tesamorelin escalated to 2 mg/day. All three compounds at research-protocol doses simultaneously. IGF-1 signal accumulates; visceral-fat metabolic effects become measurable in published Falutz-model timelines at weeks 8–12.
  • Weeks 9–12 (CJC/Ipamorelin taper — not shown above): CJC-1295 and Ipamorelin are typically reduced to twice-daily or discontinued while Tesamorelin continues to week 12 to maintain the IGF-1 and VAT-reduction signal through the full cycle.
  • Post-cycle: A 4-week washout before re-initiation. IGF-1 returns toward baseline within 6–8 weeks of tesamorelin discontinuation in published trial data.

Reconstitution & storage notes

CJC-1295 (no DAC) reconstitutes readily in bacteriostatic water at 1 mg/mL and is stable at 2–8 °C for approximately 28 days after reconstitution. Ipamorelin reconstitutes at 1–2 mg/mL and shares the same refrigerated stability window. Tesamorelin (lyophilised) should be reconstituted with the sterile diluent provided to 1 mg/mL; the reconstituted solution is stable at 2–8 °C for up to 24 hours per the approved product data — prepare daily or in small aliquots. All three peptides are susceptible to degradation by repeated freeze-thaw cycling; aliquot before storing beyond 30 days. Protect from light.

Where to source these research peptides

Each peptide in this stack has a dedicated research monograph on PeptideAuthority.co.uk and a research-grade SKU at PeptideBarn.co.uk. All compounds are sold strictly for in vitro research.

For a recomposition-focused variant that adds BPC-157 for tissue-repair and anti-inflammatory support alongside the pulsatile GH pair, see the Ipamorelin + CJC-1295 + BPC-157 Recomp Stack. For a protocol focused specifically on visceral adipose tissue reduction using tesamorelin alongside the fat-selective AOD-9604 fragment, see the Tesamorelin + AOD-9604 Visceral Fat Stack.

Frequently asked research questions

GHRH (CJC-1295) increases the *amplitude* of pituitary GH pulses; GHRP (Ipamorelin) triggers the pulse itself. Together they produce a synergistic — not additive — GH release in published animal and human research.

References

Peer-reviewed sources for the claims summarised above. Links open PubMed or the journal DOI.

  1. Bowers CY, Sartor AO, Reynolds GA, Badger TM. On the actions of the growth hormone-releasing hexapeptide, GHRP. Endocrinology. 1991;128(4) :2027-35 doi:10.1210/endo-128-4-2027 · PMID: 1848583
  2. Ghigo E, Arvat E, Muccioli G, Camanni F. Growth hormone-releasing peptides. European Journal of Endocrinology. 1997;136(5) :445-60 doi:10.1530/eje.0.1360445 · PMID: 9186261
  3. Raun K, Hansen BS, Johansen NL, et al.. Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology. 1998;139(5) :552-61 doi:10.1530/eje.0.1390552 · PMID: 9849822
  4. Johansen PB, Nowak J, Skjaerbaek C, et al.. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Hormone & IGF Research. 1999;9(2) :106-13 doi:10.1054/ghir.1999.9998 · PMID: 10373343
  5. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. 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. Journal of Clinical Endocrinology & Metabolism. 2006;91(3) :799-805 doi:10.1210/jc.2005-1536 · PMID: 16352683
  6. Jetté L, Léger R, Thibaudeau K, et al.. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats. Endocrinology. 2005;146(7) :3052-58 doi:10.1210/en.2004-1609 · PMID: 15802502
  7. Alba M, Fintini D, Bowers CY, Rogol AD. Effects of ipamorelin combined with growth hormone releasing hormone (GHRH) in adults with growth hormone deficiency. Growth Hormone & IGF Research. 2006;16(3) :159-65 doi:10.1016/j.ghir.2006.05.001 · PMID: 16806996
  8. Falutz J, Allas S, Blot K, et al.. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23) :2359-70 doi:10.1056/NEJMoa072439 · PMID: 18057338
  9. Stanley TL, Feldpausch MN, Oh J, et al.. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation. Journal of Clinical Endocrinology & Metabolism. 2014;99(7) :2390-400 doi:10.1210/jc.2014-1275 · PMID: 24758183
  10. Fourman LT, Billingsley JM, Agyapong G, et al.. Effects of tesamorelin on hepatic steatosis and the hepatic transcriptome in HIV-associated nonalcoholic fatty liver disease. Hepatology. 2020;71(5) :1530-41 doi:10.1002/hep.30918 · PMID: 31529567