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Cyclic Glycine-Proline (cGP)2 residuesGPEach bubble = one amino acid. Size = residue mass. Color = chemical class.Also known as: cGP, cyclo(Gly-Pro), cGPMAX (brand)
Stroke patients with higher cGP-to-IGF-1 ratios recover better at 90 days [1]. Cyclic glycine-proline (cGP) is a tiny endogenous metabolite your body already makes from IGF-1. It regulates how much free, active IGF-1 reaches your brain and tissues. No RCTs exist for cGP supplementation itself; the strong clinical trial data belongs to NNZ-2591, a synthetic analog dosed thousands of times higher. Still, the mechanistic story is solid, and the commercial supplement cGPMAX (40 mcg/day oral) is the only validated product on the market. Aging adults and post-stroke patients are the primary users.
Stroke patients who start with higher cGP-to-IGF-1 ratios show better neurological recovery at 90 days. That single finding (90 patients)[1] turned a niche metabolite into one of the more interesting neuroprotection targets in the peptide space. Cyclic glycine-proline, abbreviated cGP, CAS number 4300-21-3, is a 2,5-diketopiperazine with a molecular weight of 154.2 Da. Your body produces it naturally. When IGF-1 breaks down, it first yields glycine-proline-glutamate (GPE), which has a plasma half-life under four minutes. GPE rapidly converts into cGP, a far more stable cyclic structure found in plasma, cerebrospinal fluid, and breast milk. The mechanism is homeostatic. cGP competes with IGF-1 for binding to insulin-like growth factor binding protein-3 (IGFBP-3). When cGP occupies that binding site, free IGF-1 rises. When IGF-1 is already high, cGP's displacement effect is proportionally smaller. The net result is a bidirectional regulator that nudges IGF-1 toward a healthy set-point rather than flooding the system. In APP/PS1 transgenic mice (an Alzheimer's model), cGP reduced amyloid plaque burden and improved spatial memory [2]. In diet-induced obese rats, it normalized systolic blood pressure [3]. A 2023 review by Guan and colleagues [4] established the cGP/IGF-1 molar ratio as a biomarker of functional IGF-1 status in aging. The gap: no randomized placebo-controlled trial has tested cGP in humans at any dose. The 40 mcg/day supplement dose comes from the cGPMAX research team, not from a dose-ranging study. Community adoption is minimal, fewer than 10 Reddit threads total.
cGP's primary job is freeing IGF-1 from its carrier protein. Most circulating IGF-1 is locked to IGFBP-3 in an inactive state. cGP fits into IGFBP-3's binding pocket and displaces IGF-1, allowing it to reach IGF-1 receptors on target cells. Once IGF-1 binds IGF-1R, the PI3K/Akt signaling cascade activates. That pathway drives neuronal survival, synaptic plasticity, and anti-apoptotic protection. cGP also works directly on glutamate receptors. It is a positive allosteric modulator of AMPA-type receptors, boosting excitatory neurotransmission and long-term potentiation. Long-term potentiation is the cellular process behind memory formation; AMPA modulation is the same target that racetam-class nootropics aim for, though cGP binds a different site. The third arm is neurotrophic support. cGP upregulates brain-derived neurotrophic factor (BDNF) signaling, which supports dendritic growth, synaptogenesis, and neuronal resilience. Studies in human fetal neural stem cells showed dose-dependent reductions in apoptosis (programmed cell death) under oxidative stress conditions. What makes cGP unusual among peptides is its size. At 154.2 Da with a topological polar surface area of 49.4 angstroms squared, it crosses the blood-brain barrier efficiently from oral dosing. No injection required. That combination of oral bioavailability, BBB penetration, and endogenous origin is rare.
Solid preclinical evidence and strong mechanistic rationale for cGP as an endogenous IGF-1 homeostatic regulator. Human epidemiological data links higher cGP/IGF-1 ratios to better cognitive function and stroke recovery [1]. One 2025 exploratory human interventional study reports improved vascular outcomes in T2DM patients (ScienceDirect S175646462500324X). However, no randomized placebo-controlled trials exist for cGP itself: the strong clinical trial evidence belongs to NNZ-2591 (the synthetic analog), not cGP. The 40 mcg/day supplement dose is empirically derived by the cGPMAX research team; it has no dose-ranging RCT behind it.
PMID 36770687: Guan et al. 2023, "Cyclic Glycine-Proline (cGP) Normalises Insulin-Like Growth Factor-1 (IGF-1) Function: Clinical Significance in the Ageing Brain." Molecules 28(3):1021. Comprehensive review establishing the cGP/IGF-1 ratio as a biomarker of functional IGF-1 status in ageing and neurological disease. PMC9919809.
No placebo-controlled RCT for cGP itself at any dose. Epidemiological studies establish correlation (not causation) between cGP/IGF-1 ratios and outcomes. The 2025 T2DM study is exploratory and likely unblinded/uncontrolled. All Phase 2/3 clinical trial evidence belongs to NNZ-2591 at doses 4–12 mg/kg twice daily: orders of magnitude above cGP supplement doses and not directly applicable. Human PK data for cGP are essentially unpublished; the 4–6 hour half-life is a class estimate only.
Minimal independent community presence. The cGP supplement market is dominated by cGPMAX brand testimonials, which report cognitive recovery (particularly post-concussion), improved energy, and mood in Parkinson's patients, and blood pressure normalisation. No significant Reddit or biohacker forum consensus protocols exist: fewer than 10 threads across r/Nootropics and r/Peptides combined. Community awareness is low relative to the evidence base.
Science and community are not truly divergent, but community adoption is so minimal that no independent community-derived consensus exists. The 40 mcg/day dose and continuous-use protocol reflect manufacturer guidance, not community-generated experimentation. The community follows the science (via the manufacturer) rather than generating independent protocols. This is effectively a science-only compound from a community evidence standpoint.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 0.04mg | Daily |
| Moderate | 0.04mg | 2x Daily |
| Aggressive | 0.08mg | Daily |
You don't inject cGP. One capsule a day, that's it. The commercial product (cGPMAX) delivers 40 mcg per capsule. Some people take two capsules (80 mcg total) for more pronounced cognitive decline or post-concussion recovery. No reconstitution math applies here since cGP is an oral capsule product. If you're sourcing raw cGP powder instead, you'll need an analytical balance with 0.001 mg resolution. Standard milligram-calibrated scales can't measure 40 mcg accurately. Honestly, raw powder dosing at this scale is impractical for most people. The biggest thing beginners miss: cGP works on an accumulation model. You won't feel anything for weeks. The manufacturer says 90 days minimum before you can reasonably assess whether it's working. Most people who quit early leave before the compound had any chance of reaching effective tissue concentrations. Consistency matters more than timing; take it morning, evening, with food, without food, just don't skip days. Store capsules at room temperature away from light and moisture. No refrigeration needed.
The commercial supplement cGPMAX recommends at least 90 days of consistent daily use to build cGP reserves. cGP works on an accumulation basis: levels need to be gradually topped up and then maintained. There's no established cycling protocol from clinical research. Given its endogenous nature and safety profile, continuous daily use appears to be the standard approach.
cGP is an endogenous compound produced by the body and present in plasma and CSF throughout life. Supplementation is designed to normalise declining cGP/IGF-1 ratios: a process that requires accumulation, not cycling. The manufacturer (cGPMAX) and all published research recommend continuous daily use without a mandated off-cycle. The 4-week off-break in the database cycling protocol (onWeeks: 12, offWeeks: 4) has no published basis and appears to be a precautionary editorial addition. No receptor desensitisation or hormonal axis disruption mechanism applies to cGP at physiological supplement doses.
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Expected: Weeks 1–2: no perceptible effect. Weeks 3–6: possible subtle improvements in mental clarity, focus, and sleep. Weeks 6–12: more consistent cognitive benefits, memory recall, stress resilience. 3–6 months: normalised cGP/IGF-1 ratio; sustained cognitive and potentially cardiovascular benefits.
Monitor: No bloodwork strictly required. Optional: measure serum IGF-1 at baseline and 12 weeks to assess functional IGF-1 availability. Track cognitive self-assessment (memory, focus, verbal recall) weekly. Blood pressure tracking is worthwhile for hypertensive users given the rat BP normalisation data.
No water volume, reconstitution, or syringe required.
Morning or evening, with or without food. Pick a consistent time so you don't forget doses.
For the standard protocol, take one capsule daily for a minimum of 90 continuous days before assessing effects.
If your physician or the severity of your symptoms warrants a higher dose, take two capsules daily (80 mcg total). You can take both at once or split them (one AM, one PM).
Storage: room temperature (15 to 25 degrees Celsius), dry place, away from direct light. No refrigeration.
If sourcing raw powder, you'll need a precision analytical balance (0.001 mg resolution minimum) to measure 40 mcg. A standard milligram scale is wholly inadequate at this dose level.
Track your response with a weekly cognitive self-assessment (memory, focus, verbal fluency, mental clarity). cGP changes are gradual; a weekly log captures the trajectory that day-to-day observation misses.
No dose adjustment needed relative to any other route; oral is the studied and marketed route
cGPMAX capsules (40 mcg) are the only validated oral formulation. Raw powder can be dissolved in water but accurate microgram dosing is extremely difficult without precision equipment.
Unknown: no nasal bioavailability data; community has not explored this route
Intranasal route is speculative and not studied for cGP. No dose recommendations available. Stick to oral unless future research establishes intranasal protocols.
Complementary BDNF upregulation via different mechanisms: Semax activates BDNF/TrkB directly via ACTH/MSH-like activity; cGP increases bioavailable IGF-1 which also upregulates BDNF signalling. Additive neurotrophic profile without competing pathways.
cGP 40 mcg/day oral (continuous) + Semax 200–600 mcg intranasal daily or as needed
Same rationale as Semax but with longer intranasal duration and stronger BDNF upregulation. NA-Semax adds anxiolytic properties from the Semax backbone, complementing cGP's cognitive support profile.
cGP 40 mcg/day oral (continuous) + NA-Semax 200–300 mcg intranasal daily
Anxiolytic and cognitive complement: Selank modulates GABA-A and BDNF; cGP modulates IGF-1/AMPA. Non-overlapping mechanisms; community rationale is stress + cognitive support combination.
cGP 40 mcg/day oral + Selank 250–500 mcg intranasal daily
Blackcurrant anthocyanins increase endogenous cGP levels in CSF (PMID 29865234). Used as a natural adjunct to raise baseline cGP when direct supplementation is unavailable or as a cost-reduction strategy. Effect magnitude is smaller than direct cGP supplementation.
Standardized blackcurrant anthocyanin extract 300–600 mg/day oral
Complex and unstudied IGFBP-3 competition dynamics. Both cGP and IGF-1 LR3 displace native IGF-1 from IGFBP-3, but via different mechanisms. The combined effect on free IGF-1 bioavailability is unpredictable and could push beyond homeostatic ranges, particularly relevant for cancer-risk populations.
GH drives IGF-1 and IGFBP-3 production. Adding cGP (which displaces IGF-1 from IGFBP-3) on top of GH creates an amplified and unstudied free-IGF-1 elevation. In individuals with any IGF-1-sensitive condition, this interaction is potentially dangerous.
cGP is a positive allosteric modulator of AMPA receptors. Combining with other AMPA-positive compounds (e.g., aniracetam, farampator) creates theoretical additive excitatory load. No human data: risk level is speculative but warrants caution.
Pricing updated 2026-04-09
The IGF-1 cancer risk is the most important safety consideration with cGP. Because cGP increases free bioavailable IGF-1 by displacing it from IGFBP-3, anyone with an active IGF-1-receptor-positive cancer (some breast, prostate, and colon cancers) faces a real contraindication. This is not a generic legal disclaimer. Raised bioavailable IGF-1 can feed tumor growth in IGF-1R-positive malignancies. Anyone with active cancer or a cancer history should consult an oncologist before using cGP. Beyond the cancer concern, the published safety profile is remarkably clean. No adverse events have been reported in any published cGP study. The commercial supplement cGPMAX has been used daily at 40 mcg without reported side effects across its customer base. The synthetic analog NNZ-2591, which shares cGP's core mechanism but at massively higher doses (4 to 12 mg/kg twice daily), completed Phase 2 clinical trials with an acceptable safety profile. That's reassuring context, though NNZ-2591 results don't transfer directly. The human evidence base is small, though. There are no placebo-controlled trials specifically for cGP supplementation. Community reports number fewer than 10 Reddit threads. So the absence of reported side effects could partly reflect the absence of people taking it and reporting back. That's different from "proven safe in thousands of users." Mild headache and GI discomfort are theoretically possible at higher doses. cGP's endogenous origin (your body already makes it) and the small supplement dose (40 to 80 mcg/day) make severe adverse reactions unlikely, but "unlikely" and "impossible" are different words. Combining cGP with exogenous IGF-1 or growth hormone therapy creates unstudied free-IGF-1 elevations. The interaction hasn't been characterized in any study. Stacking with other AMPA receptor modulators (racetams, ampakines) adds a theoretical excitatory load concern; no human data exist on this combination either. Pregnancy and breastfeeding: insufficient controlled safety data. cGP is found naturally in breast milk, but supplementation during pregnancy has not been studied. Stop use and consult a physician if you develop any signs of an IGF-1-sensitive condition, experience persistent headaches, or begin exogenous GH/IGF-1 therapy.
Verify Cyclic Glycine-Proline (cGP) dosing and safety with a second opinion
cGP is available as an oral supplement (cGPMAX) or as raw research-grade powder from peptide vendors. cGPMAX is the only commercially validated formulation with confirmed per-capsule dosing (40 mcg). Raw cGP powder from research vendors poses significant accuracy risk: at microgram-scale dosing, even milligram-calibrated lab balances cannot reliably measure 40 mcg quantities, making underdosing or inconsistent dosing highly probable. Purity and source authenticity of raw powder products vary widely.
| Test | When | Target |
|---|---|---|
| Serum IGF-1 | Baseline; 12 weeks; 24 weeks | Age-appropriate reference ranges (consult lab); aim for mid-normal for age, not supraphysiological |
| Blood Pressure (systolic/diastolic) | Baseline; every 4 weeks during first 3 months | Systolic <130 mmHg, diastolic <80 mmHg (general adult standard) |
| Cognitive self-assessment log | Weekly during first 12 weeks; monthly thereafter | — |
| HbA1c / fasting glucose (T2DM or metabolic syndrome users) | Baseline; 3 months; 6 months | HbA1c <7.0% (T2DM management target); trend improvement is the goal |
cGP increases free (bioavailable) IGF-1 by displacing it from IGFBP-3. Monitoring total serum IGF-1 provides a partial proxy for the cGP/IGF-1 homeostatic shift, though the cGP/IGF-1 molar ratio (not routinely measured clinically) is the actual research biomarker.
The 2019 rat study (PMID 31753784) and 2025 T2DM exploratory study show cGP normalises BP in metabolically compromised subjects. Tracking BP is the most tractable cardiovascular marker for supplement users.
No blood biomarker reliably tracks cognitive improvement from cGP. Structured weekly self-rating of memory, focus, verbal fluency, and mental clarity is the primary endpoint for supplement users and is consistent with cGP's accumulation timeline.
The 2025 exploratory T2DM study reports cGP improved HbA1c% and vascular endpoints. Diabetic users should track glycaemic control throughout supplementation.
Minimal noticeable effects. cGP begins accumulating in plasma and CSF. The compound is building toward effective tissue concentrations.
Some users report subtle improvements in mental clarity, focus, and sleep quality as cGP/IGF-1 ratios begin to shift and IGF-1 bioavailability increases.
More consistent cognitive benefits become apparent. Improved memory recall, better stress resilience, and enhanced mental sharpness. Blood pressure normalization may be measurable in those with elevated levels.
Full accumulation effects. Sustained improvements in cognitive performance, neuroprotective benefits ongoing. The cGP/IGF-1 ratio should be normalized, supporting healthy IGF-1 function long-term.
Weeks 1 to 2: Nothing noticeable. cGP is building up in plasma and cerebrospinal fluid. Tissue concentrations haven't reached the threshold for measurable IGF-1 displacement yet. This is normal. Don't assess efficacy at this point. Weeks 3 to 6: Some users report subtle shifts in mental clarity, focus, or sleep quality. The cGP/IGF-1 molar ratio starts moving as cGP occupies more IGFBP-3 binding sites. Individual variability runs high; many people still feel nothing until week 8 or later. Weeks 6 to 12: Benefits become more consistent. Improved memory recall, better stress resilience, sharper mental focus. Hypertensive users tracking blood pressure may see modest reductions. Post-concussion users (based on cGPMAX testimonials) report improved word retrieval and conversational fluency at this stage. 3 to 6 months: Full accumulation. The cGP/IGF-1 ratio should be normalized toward a healthier set-point. Sustained cognitive performance improvements. Energy and mood stabilize at a higher baseline, particularly for users with Parkinson's-related decline. The 2025 exploratory T2DM study reported protective foot sensation, blood pressure normalization, and reduced macroalbuminuria at this timeframe.
cGP begins accumulating in plasma and CSF. Tissue concentrations are building but remain below the threshold for measurable IGF-1/IGFBP-3 displacement.
No effects reported in the first 1–2 weeks. Users who expect rapid onset frequently discontinue too early: this is the most common reason for abandonment.
The cGP/IGF-1 molar ratio begins to shift. Bioavailable IGF-1 increases incrementally as IGFBP-3 binding sites become partially occupied by cGP.
Subtle improvements in mental clarity, focus, and sleep quality reported by some users. Individual variability is high: many users report nothing until week 8+.
IGF-1/IGFBP-3 homeostasis normalising. AMPA receptor modulation and BDNF upregulation producing measurable synaptic plasticity improvements in preclinical models. Blood pressure normalisation observed in animal studies by this timepoint.
More consistent cognitive benefits: improved memory recall, better stress resilience, sharper mental focus. Blood pressure tracking shows modest reductions in hypertensive users. Post-concussion users (cGPMAX testimonials) report improved word retrieval and conversational fluency.
The cGP/IGF-1 ratio normalised toward a healthier set-point. Sustained neuroprotective signalling via IGF-1R/PI3K/Akt pathways. The 2025 exploratory T2DM study suggests protective foot sensation, BP normalisation, and reduced macroalbuminuria at this timeframe.
Sustained cognitive performance improvements. Energy and mood maintained at higher baseline (Parkinson's-affected users). cGPMAX testimonials describe results as "like clearing brain fog" after months of consistent use.
Source: Estimated from diketopiperazine class stability data; cGP is enzymatically stable unlike precursor GPE (t½ <4 min). Specific cGP plasma half-life not yet characterized in published human PK studies.
Loading the interactive decay curve.
cGP is classified as a dietary supplement, not a pharmaceutical. It has no FDA approval for any indication. The FDA has not evaluated cGP for the treatment, cure, or prevention of any disease. Regulatory status is preclinical. The primary commercial product, cGPMAX, is manufactured in New Zealand and sold internationally as a dietary supplement. It is legally available for purchase in most countries without prescription. cGP is not a controlled substance in the United States, European Union, United Kingdom, Australia, or New Zealand. NNZ-2591 (trofinetide's structural relative), the synthetic analog of cGP developed by Neuren Pharmaceuticals, is in Phase 2 clinical trials for neurodevelopmental disorders. NNZ-2591 is an investigational drug; cGP itself is not. Athletes should note that cGP modulates IGF-1 bioavailability. WADA status for cGP specifically has not been adjudicated, but any compound that modulates IGF-1 activity could draw scrutiny under the growth factor manipulation category. Competitive athletes should verify with their sport's anti-doping authority before use. This content is for educational purposes only and does not constitute medical advice.
Peptide Schedule Research TeamReviewed Apr 20267 Citations
