The GH Optimization Stack: CJC-1295 + Ipamorelin
Last updated: 2026-02-20
The CJC-1295 and Ipamorelin growth hormone optimization stack is one of the most well-established peptide combinations for stimulating natural growth hormone (GH) release. By pairing a long-acting growth hormone-releasing hormone (GHRH) analog with a selective ghrelin receptor agonist (GH secretagogue), this protocol activates two distinct pathways of the GH axis to produce amplified, pulsatile growth hormone release.
CJC-1295 (with or without DAC) extends the duration of GHRH signaling at the pituitary, while ipamorelin triggers GH release through the ghrelin/GHS-R1a receptor pathway with remarkable selectivity—unlike older GH secretagogues, ipamorelin does not significantly increase cortisol, prolactin, or appetite.[1] When combined, research suggests these peptides produce GH elevation that is significantly greater than either compound alone, as they stimulate GH release through complementary receptor pathways.[2]
This guide covers the complete protocol including dosage schedules, timing, cycle guidelines, expected effects, safety considerations, and the research behind each compound. All information is for educational purposes only and should not be interpreted as medical advice.
Compounds in This Stack
CJC-1295
Extended GHRH signaling, sustained GH elevation, IGF-1 amplification
CJC-1295 is a synthetic analog of growth hormone-releasing hormone (GHRH) with amino acid substitutions that dramatically extend its half-life compared to native GHRH. It is available in two forms: CJC-1295 with DAC (Drug Affinity Complex) for once-weekly dosing, and CJC-1295 without DAC (also called Modified GRF 1-29 or Mod GRF) for multiple-times-daily dosing.
Mechanism in this stack: CJC-1295 binds to the GHRH receptor (GHRH-R) on somatotroph cells in the anterior pituitary gland, stimulating GH synthesis and secretion. The modified amino acid sequence resists enzymatic degradation by dipeptidyl peptidase IV (DPP-IV), extending its biological activity. CJC-1295 effectively increases the baseline amplitude of GH pulses and elevates IGF-1 levels in a dose-dependent manner.[2]
| Parameter | CJC-1295 (no DAC / Mod GRF 1-29) | CJC-1295 with DAC |
|---|---|---|
| Research Dosage | 100–300 mcg per injection | 2 mg once per week |
| Frequency | 1–3 times daily | Once weekly |
| Half-Life | ~30 minutes | ~8 days (due to albumin binding) |
| Injection Route | Subcutaneous | Subcutaneous |
| IGF-1 Increase | Moderate, pulsatile pattern | Sustained elevation (up to 2–3x baseline) |
Note: Most stack protocols use CJC-1295 without DAC (Mod GRF 1-29) because it produces a more natural pulsatile GH release pattern that better mimics endogenous GHRH. The DAC version creates more sustained GH elevation, which some researchers consider less physiological. The protocol below uses the no-DAC version by default.
Ipamorelin
Selective GH secretagogue, pulsatile GH release, no cortisol/prolactin impact
Ipamorelin is a pentapeptide GH secretagogue that activates the ghrelin receptor (GHS-R1a) in the pituitary gland. It is considered the most selective GH-releasing peptide available, producing robust GH release without the significant cortisol, prolactin, or appetite increases seen with older secretagogues like GHRP-6 and GHRP-2.[1]
Mechanism in this stack: Ipamorelin binds to the GHS-R1a receptor on pituitary somatotrophs, triggering GH release through a pathway that is distinct from and additive to the GHRH receptor pathway used by CJC-1295. This dual-pathway activation is the foundation of the stack's synergy: CJC-1295 tells the pituitary to produce more GH, while ipamorelin triggers the actual release of stored GH. The result is a significantly amplified GH pulse compared to either peptide alone.[3]
| Parameter | Detail |
|---|---|
| Research Dosage | 100–300 mcg per injection |
| Frequency | 1–3 times daily |
| Half-Life | ~2 hours |
| Injection Route | Subcutaneous |
| Selectivity | Minimal cortisol, prolactin, or appetite stimulation |
| GH Release Pattern | Sharp pulse, mimicking natural GH rhythm |
How They Work Together
The CJC-1295 + Ipamorelin stack exploits a well-characterized biological principle: growth hormone release is controlled by two opposing hypothalamic signals—GHRH (stimulatory) and somatostatin (inhibitory). By activating both the GHRH pathway and the ghrelin pathway simultaneously, this stack produces GH release that is meaningfully greater than either peptide alone.
Dual-Pathway GH Amplification
The pituitary somatotroph cell has two key receptors for GH release: the GHRH receptor (activated by CJC-1295) and the GHS-R1a ghrelin receptor (activated by ipamorelin). These receptors use different intracellular signaling cascades:
- CJC-1295 (GHRH pathway): Activates adenylyl cyclase → increases cAMP → activates protein kinase A → stimulates GH gene transcription and GH vesicle release
- Ipamorelin (ghrelin pathway): Activates phospholipase C → increases IP3 and DAG → raises intracellular calcium → directly triggers exocytosis of GH-containing vesicles
Because these are separate signaling cascades, their combined effect is additive to synergistic. CJC-1295 increases GH synthesis and primes the somatotroph with more GH-containing vesicles, while ipamorelin triggers the acute release of those vesicles. Research in animal models has demonstrated that co-administration of GHRH and ghrelin-mimetic peptides produces GH peaks approximately 2–3 times higher than either agent alone.[3]
Ipamorelin's Somatostatin Antagonism
An additional synergistic mechanism involves somatostatin—the hypothalamic hormone that suppresses GH release. Ghrelin-pathway peptides like ipamorelin have been shown to functionally antagonize somatostatin signaling at the pituitary level. This means ipamorelin not only directly triggers GH release but also removes the natural "brake" on GH secretion, allowing CJC-1295's GHRH signaling to be more effective. This somatostatin-antagonism effect is a key reason the combination outperforms individual administration.[1]
Preserved Pulsatility
Unlike exogenous HGH injections (which provide a flat bolus of synthetic growth hormone), the CJC-1295 + Ipamorelin stack amplifies the body's own GH pulse pattern. This is significant because pulsatile GH release is how the body naturally operates—GH is secreted in 6–8 pulses per day, with the largest pulse occurring during deep sleep. Maintaining this pulsatile pattern is thought to be important for:
- Preserving GH receptor sensitivity (preventing downregulation)
- Maintaining the body's negative feedback loop (preventing pituitary suppression)
- Optimizing the GH-to-IGF-1 conversion ratio in the liver
- Reducing the risk of side effects associated with sustained supraphysiological GH levels
Ipamorelin's Clean Selectivity Profile
One of the most notable advantages of this particular stack is ipamorelin's selectivity. Earlier GH secretagogues like GHRP-6 and GHRP-2 also activate the ghrelin receptor but produce significant side effects including intense hunger (GHRP-6), elevated cortisol, and increased prolactin. Ipamorelin achieves comparable GH release with minimal impact on these other hormones, making it the preferred ghrelin-pathway peptide for stacking with CJC-1295.[1]
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Protocol & Dosage Schedule
Dosage Schedule
| Protocol Variant | CJC-1295 (no DAC) | Ipamorelin | Timing |
|---|---|---|---|
| Standard (1x/day) | 100–200 mcg | 100–200 mcg | Before bed (30 min pre-sleep) |
| Moderate (2x/day) | 100–200 mcg each | 100–200 mcg each | Morning (fasted) + Before bed |
| Aggressive (3x/day) | 100 mcg each | 100 mcg each | Morning (fasted) + Post-workout + Before bed |
| With DAC variant | CJC-1295 DAC: 2 mg once/week | 200–300 mcg at bedtime daily | CJC: set day weekly; Ipa: nightly |
Cycle Length
12–16 weeks is the most commonly referenced cycle length for the CJC-1295 + Ipamorelin stack. Some protocols suggest ongoing use with periodic breaks (e.g., 5 days on / 2 days off, or 3 months on / 1 month off) to prevent receptor desensitization. After completing a full cycle, a minimum 4-week off period is generally recommended. IGF-1 levels typically return to baseline within 2–4 weeks of cessation.
Timing & Administration
Critical timing rules:
- Fasted state required: Both peptides should be administered on an empty stomach—at least 2 hours after eating and 30–45 minutes before eating. Elevated blood sugar and insulin blunt GH release significantly, which would undermine the entire purpose of the stack.
- Pre-sleep dose is most important: If only dosing once daily, the bedtime dose is preferred because it coincides with the body’s natural nocturnal GH surge. Amplifying this endogenous pulse produces the largest GH increase.
- Post-workout window: For the 2x or 3x daily protocol, a post-workout dose leverages the natural GH spike triggered by exercise. Wait at least 30 minutes post-workout before injecting.
Combined injection protocol: CJC-1295 and ipamorelin are typically mixed in the same syringe and injected together as a single subcutaneous injection. This is both convenient and scientifically appropriate, as simultaneous administration ensures both receptors are activated at the same time for maximum synergy.
Sample daily schedule (2x/day protocol):
- 6:00 AM – Wake up (fasted)
- 6:15 AM – Inject CJC-1295 100–200 mcg + Ipamorelin 100–200 mcg (combined)
- 6:45–7:00 AM – Eat breakfast (30+ min after injection)
- 10:00 PM – Last food intake (2+ hours before bed dose)
- 11:30 PM – Inject CJC-1295 100–200 mcg + Ipamorelin 100–200 mcg (combined)
- 12:00 AM – Sleep
What to Expect
Growth hormone optimization produces gradual, cumulative effects. Unlike peptides that target acute injury, the benefits of the CJC-1295 + Ipamorelin stack build over weeks to months as sustained GH elevation drives downstream changes in body composition, recovery, and tissue quality.
| Timeframe | Expected Observations |
|---|---|
| Week 1–2 | Improved sleep quality and depth. Vivid dreams (common indicator of elevated nocturnal GH). Mild water retention as GH increases intracellular water. Subtle increase in energy and recovery rate. |
| Weeks 3–4 | Noticeable improvement in recovery from exercise. Improved skin quality and hydration. Beginning of body composition changes (subtle fat loss, especially visceral). IGF-1 levels measurably elevated on blood work. |
| Weeks 5–8 | Measurable fat loss, particularly in the abdominal area. Improved lean muscle tone and fullness. Better exercise performance and workout recovery. Improved joint comfort and connective tissue quality. Enhanced skin elasticity and hair quality. |
| Weeks 8–12 | Peak body composition changes. Notable reduction in visceral fat. Continued lean mass improvements. Substantial improvements in skin, hair, and nail quality. Optimal recovery between workouts. |
| Weeks 12–16 | Continued refinement of body composition. Full expression of anti-aging benefits. Assessment point for cycle continuation or completion. Blood work recommended to verify IGF-1 levels remain in healthy range. |
Safety & Contraindications
Known Side Effects
The CJC-1295 + Ipamorelin stack has a favorable safety profile compared to exogenous HGH, largely because it amplifies the body’s own GH production rather than replacing it. However, side effects can occur, particularly at higher dosages.
CJC-1295 reported side effects:
- Injection site reactions (redness, itching, mild pain)
- Facial flushing and warmth shortly after injection
- Mild water retention, especially in the first 2 weeks
- Tingling or numbness in extremities (sign of elevated GH)
- Increased appetite
Ipamorelin reported side effects:
- Mild headache (typically transient)
- Lightheadedness immediately after injection
- Mild nausea (infrequent)
- Transient fatigue or drowsiness (particularly with bedtime dosing)
GH-elevation side effects (both compounds):
- Carpal tunnel-like symptoms (wrist/hand tingling) at higher doses—indicates supraphysiological GH levels; reduce dosage
- Joint stiffness or mild edema from water retention
- Increased blood glucose (GH is a counter-regulatory hormone to insulin)—monitor if prediabetic or diabetic
Contraindications and Cautions
- Cancer history: Growth hormone and IGF-1 promote cell proliferation. Individuals with active cancer or a history of GH-dependent tumors should not use this stack. Elevated IGF-1 has been associated with increased risk of certain cancers in epidemiological studies, though a causal relationship in the context of peptide-stimulated GH release has not been established.
- Diabetes or insulin resistance: GH is a counter-regulatory hormone that raises blood glucose. Individuals with type 2 diabetes or significant insulin resistance should use this stack only under medical supervision and monitor glucose levels closely.
- Pregnancy and breastfeeding: No safety data exists. Avoid use entirely.
- Under 25 years old: Natural GH production is typically at or near peak levels in young adults. Exogenous stimulation is generally unnecessary and could disrupt the developing endocrine system.
- Pituitary disorders: This stack works by stimulating the pituitary gland. Individuals with pituitary tumors, hypopituitarism, or other pituitary conditions should consult an endocrinologist before use.
Monitoring Recommendations
Blood work is recommended at baseline, 4–6 weeks, and end-of-cycle. Key markers to monitor include:
- IGF-1: Primary marker of GH status. Target: upper-normal range for age. Levels above the normal range warrant dosage reduction.
- Fasting glucose and HbA1c: Monitor for GH-induced insulin resistance.
- Fasting insulin: Assess whether GH elevation is affecting insulin sensitivity.
- Complete metabolic panel: General health monitoring.
Important: Neither CJC-1295 nor ipamorelin is FDA-approved for anti-aging, muscle building, or body composition purposes. These are research compounds. This information is for educational purposes only and should not be construed as medical advice. Always consult a qualified healthcare professional before beginning any peptide protocol.
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Frequently Asked Questions
References
- Raun K, Hansen BS, Johansen NL, et al.. Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology, 1998.
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Bhatt RS. 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.
- Bowers CY, Granda R, Mohan S, Kuipers J, Baylink D, Veldhuis JD. Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) with combination GHRH and GH-releasing peptide (GHRP) administration. Journal of Clinical Endocrinology & Metabolism, 2004.
- Veldhuis JD, Keenan DM, Bailey JN, Adeniji A, Miles JM, Paulo R, Cosma M, Soares-Welch C. Testosterone supplementation in older men restrains insulin-like growth factor's dose-dependent feedback inhibition of pulsatile growth hormone secretion. Journal of Clinical Endocrinology & Metabolism, 2009.
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Journal of Clinical Endocrinology & Metabolism, 2006.
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Our content is reviewed for accuracy and grounded in peer-reviewed research where available. We do not provide medical advice. Always consult a qualified healthcare professional.