Overview
Overview
Pinealon is a synthetic tripeptide bioregulator (Glu‑Asp‑Arg) developed as part of Professor Vladimir Khavinson’s extensive peptide research program[1][2]. This neuroprotective peptide is studied for its ability to protect neurons from oxidative stress, support cognitive function, and modulate gene expression in brain tissue[3][4]. This educational protocol presents a once‑daily subcutaneous approach using a practical dilution for clear insulin‑syringe measurements. Reconstitute: Add 3.0 mL bac
- Category
- Cognitive
- Routes
- subcutaneous
Mechanism
Pinealon
Mechanism of action
Mechanism of action
Pinealon is unusually small. At about 418 g/mol it is one of the smallest peptides used in neurological research. Khavinson's group has proposed that this small size lets Pinealon pass through cell membranes, including the nuclear membrane, and interact directly with DNA. In plain English: most peptides plug into a receptor on the cell surface and trigger a signal from there. Pinealon is proposed to act more like a small key that slips inside the cell, reaches the nucleus, and helps switch certain genes on or off. The genes involved are linked to antioxidant defense and neuron survival. The technical name for this proposed effect is epigenetic regulation through gene promoter binding . The leading hypothesis is that the Glu-Asp-Arg sequence binds to promoter regions and helps the cell make more of certain proteins. This mechanism is supported by preclinical work but has not been confirmed in large human trials. In rat cerebellar granule cells, neutrophils, and PC12 cells, Pinealon limited the buildup of reactive oxygen species under oxidative stress (Khavinson et al., Rejuvenation Research, 2011). The same study described a delayed activation of the ERK 1/2 signaling pathway and changes in the cell cycle. In a mouse hippocampal neuron model of Alzheimer's amyloid toxicity, EDR (200 ng/mL) increased mushroom dendritic spines by 71%, returning the parameter close to normal (Kraskovskaya et al., 2017).
Key research findings
- 01
Pinealon (Glu-Asp-Arg / EDR) dose-dependently restricted reactive oxygen species accumulation and reduced necrotic cell death in cerebellar granule cells, neutrophils, and PC12 cells under oxidative stress, with delayed ERK1/2 activation (Khavinson et al., 2011, Rejuvenation Research; PMID 21978084, DOI 10.1089/rej.2011.1172).
- 02
Fluorescence-labeled Pinealon entered the nucleus of HeLa cells and bound DNA sequence-selectively; NMR/molecular-dynamics work indicates major-groove interaction with guanine, supporting a proposed gene-expression mechanism (Fedoreyeva et al., 2011, Biochemistry Moscow, PMID 22117547, DOI 10.1134/S0006297911110022; Silanteva et al., 2019, J Phys Chem B, PMID 30762356, DOI 10.1021/acs.jpcb.8b10359).
- 03
EDR stimulated serotonin-related gene expression in aging rat cortical cultures, and in human fibroblast-derived induced neurons from elderly donors it reduced oxidative DNA damage and increased dendritic arborization (Khavinson et al., 2014, Bull Exp Biol Med, PMID 24909721, DOI 10.1007/s10517-014-2496-y; Kraskovskaya et al., 2024, Int J Mol Sci, PMID 39518916, DOI 10.3390/ijms252111363).
- 04
In rat offspring exposed to prenatal hyperhomocysteinemia, Pinealon was associated with improved spatial learning and cerebellar neurons more resistant to oxidative stress; other rodent work reports antihypoxic effects and caspase-3 modulation (Arutjunyan et al., 2012, Int J Clin Exp Med, PMID 22567179; Kozina, 2008, PMID 18546825; Mendzheritsky et al., 2013, PMID 28976148).
- 05
Small, largely non-randomized Russian-language cohort studies in older adults and occupational groups (often combined with other peptides) reported changes in composite biological-age and psycho-emotional indices, with one cohort also noting prooxidant signals and reduced circulating CD34+ cells (Meshchaninov et al., 2015, PMID 26390612; Bashkireva & Artamonova, 2012, PMID 23734521).
- 06
Reviews summarize proposed targets (MAPK/ERK, caspase-3, p53, SOD2, GPX1, PPARs), but a 2026 peptide review notes a current lack of clinical trials for this class, so mechanistic models outpace controlled human evidence (Khavinson et al., 2020, Molecules, PMID 33396470, DOI 10.3390/molecules26010159; Rahman et al., 2026, JAAOS Glob Res Rev, PMID 41490200, DOI 10.5435/JAAOSGlobal-D-25-00236).
Primary source: Human (small, Russian-language): Oral Pinealon plus standard therapy in 72 patients with consequences of traumatic brain injury and cerebrasthenia. Reported improvements in memory, headache duration, emotional balance, and performance. Cell-culture: Dose-dependent reduction of reactive oxygen species and necrotic cell death in cerebellar granule cells, neutrophils, and PC12 cells (Khavinson et al., Rejuvenation Research, 2011). Cell-culture (Alzheimer's model): EDR at 200 ng/mL restored mushroom dendritic spines in mouse hippocampal neurons exposed to amyloid (Kraskovskaya et al., 2017). Rat (prenatal hyperhomocysteinemia): Pinealon improved offspring spatial learning and reduced oxidative damage in cerebellar neurons (Arutjunyan et al., 2012). Rat (experimental diabetes): Pinealon supported learning retention and altered hippocampal NMDA receptor subunit expression (Karantysh et al., Neurochemical Journal, 2020).
Researched Effects
Researched benefits
Areas of active research and investigation. Results may vary and are based on preclinical or early clinical data.
Neuroprotective effects through reduction of oxidative stress and preservation of neuronal viability[3][9].
Improvements in memory, learning capacity, and cognitive function in both animal and human studies[6][10][11].
Modulation of caspase‑3 activity may reduce apoptosis in neurons and other tissues[12][13].
Potential support for circadian rhythm regulation and pineal gland function[14].
Protocol Reference
Protocol reference
Commonly cited research range: 1–2 mg, daily.
Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.
Cited protocol & reconstitution guide
Source-backed reference fields by phase, including any volume fields authored in the cited guide.
Days 1–5
1.0 mg
Days 6–14
1.5 mg
Days 15–20
2.0 mg
Full cycle (10–20 days, planning range)
1.0 to 2.0 mg per day
| Phase | Reference amount | Units / volume |
|---|---|---|
| Days 1–5 | 1.0 mg | 15 units (0.15 mL) |
| Days 6–14 | 1.5 mg | 22.5 units (0.22 mL) |
| Days 15–20 | 2.0 mg | 30 units (0.30 mL) |
| Full cycle (10–20 days, planning range) | 1.0 to 2.0 mg per day | 15–30 units (0.15–0.30 mL) |
Titration protocol
- Days 1–5Start1.0 mg
Once daily; 15 units (0.15 mL) on a U-100 syringe at 6.67 mg/mL.
- Days 6–14Build1.5 mg
Once daily; 22.5 units (0.225 mL).
- Days 15–20Build2.0 mg
Once daily; 30 units (0.30 mL); rotate injection sites (abdomen, outer thigh, back of upper arm).
- Cycle plan (10–20 days)Maintenance1.0 to 2.0 mg per day
Once daily, usually morning or early afternoon; cycle extendable to 28 days in some sources; off period of 2 to 3 months between cycles.
Storage & Handling
Storage requirements(typical for most peptides)
Can be stored for extended periods. Protect from moisture.
Store in refrigerator door. Never freeze after reconstitution.
Label vials with reconstitution date. Discard if cloudy.
Reconstitution steps
- 01🌡️Wipe the vial top: fresh alcohol swab on the rubber stopper of both the Pinealon vial and the BAC water vial.
- 02🧴Draw 3 mL bacteriostatic water into a sterile syringe — this 20 mg vial yields 6.67 mg/mL.
- 03💉Add slowly: let the water run down the inside wall of the glass, not directly onto the powder.
- 04💧Swirl, do not shake: gently swirl or roll the vial between hands until the powder dissolves into a clear solution.
- 05🔄Inspect: solution should be clear and free of cloudy particles; if it looks off, do not use the vial.
- 06🏷️Label and refrigerate: write the reconstitution date on the vial; store at 2 to 8 C (35.6 to 46.4 F).
- 07❄️Draw your dose: fresh U-100 insulin syringe per session; match the unit mark to the table for the chosen concentration.
- 08💉Important: This guide is for educational purposes only and is not medical advice. For research use only. Not for human consumption.
Additional storage notes
-4 °F (-20 °C) — Best for long-term storage. Keep dry and dark.
35.6 to 46.4 °F (2 to 8 °C) — Acceptable for short transit windows.
35.6 to 46.4 °F (2 to 8 °C) — Refrigerate. Use within the BAC water shelf window.
Clear after mixing — Cloudy or particulate solution means stop using it.
Clinical Evidence
Clinical evidence
Preclinical research from the Khavinson bioregulator program reports neuroprotective and antioxidant activity in cell and animal models.
Human (small, Russian-language): Oral Pinealon plus standard therapy in 72 patients with consequences of traumatic brain injury and cerebrasthenia. Reported improvements in memory, headache duration, emotional balance, and performance. Cell-culture: Dose-dependent reduction of reactive oxygen species and necrotic cell death in cerebellar granule cells, neutrophils, and PC12 cells (Khavinson et al., Rejuvenation Research, 2011). Cell-culture (Alzheimer's model): EDR at 200 ng/mL restored mushroom dendritic spines in mouse hippocampal neurons exposed to amyloid (Kraskovskaya et al., 2017). Rat (prenatal hyperhomocysteinemia): Pinealon improved offspring spatial learning and reduced oxidative damage in cerebellar neurons (Arutjunyan et al., 2012). Rat (experimental diabetes): Pinealon supported learning retention and altered hippocampal NMDA receptor subunit expression (Karantysh et al., Neurochemical Journal, 2020).
- 01Pinealon (Glu-Asp-Arg / EDR) dose-dependently restricted reactive oxygen species accumulation and reduced necrotic cell death in cerebellar granule cells, neutrophils, and PC12 cells under oxidative stress, with delayed ERK1/2 activation (Khavinson et al., 2011, Rejuvenation Research; PMID 21978084, DOI 10.1089/rej.2011.1172).
- 02Fluorescence-labeled Pinealon entered the nucleus of HeLa cells and bound DNA sequence-selectively; NMR/molecular-dynamics work indicates major-groove interaction with guanine, supporting a proposed gene-expression mechanism (Fedoreyeva et al., 2011, Biochemistry Moscow, PMID 22117547, DOI 10.1134/S0006297911110022; Silanteva et al., 2019, J Phys Chem B, PMID 30762356, DOI 10.1021/acs.jpcb.8b10359).
- 03EDR stimulated serotonin-related gene expression in aging rat cortical cultures, and in human fibroblast-derived induced neurons from elderly donors it reduced oxidative DNA damage and increased dendritic arborization (Khavinson et al., 2014, Bull Exp Biol Med, PMID 24909721, DOI 10.1007/s10517-014-2496-y; Kraskovskaya et al., 2024, Int J Mol Sci, PMID 39518916, DOI 10.3390/ijms252111363).
- 04In rat offspring exposed to prenatal hyperhomocysteinemia, Pinealon was associated with improved spatial learning and cerebellar neurons more resistant to oxidative stress; other rodent work reports antihypoxic effects and caspase-3 modulation (Arutjunyan et al., 2012, Int J Clin Exp Med, PMID 22567179; Kozina, 2008, PMID 18546825; Mendzheritsky et al., 2013, PMID 28976148).
- 05Small, largely non-randomized Russian-language cohort studies in older adults and occupational groups (often combined with other peptides) reported changes in composite biological-age and psycho-emotional indices, with one cohort also noting prooxidant signals and reduced circulating CD34+ cells (Meshchaninov et al., 2015, PMID 26390612; Bashkireva & Artamonova, 2012, PMID 23734521).
- 06Reviews summarize proposed targets (MAPK/ERK, caspase-3, p53, SOD2, GPX1, PPARs), but a 2026 peptide review notes a current lack of clinical trials for this class, so mechanistic models outpace controlled human evidence (Khavinson et al., 2020, Molecules, PMID 33396470, DOI 10.3390/molecules26010159; Rahman et al., 2026, JAAOS Glob Res Rev, PMID 41490200, DOI 10.5435/JAAOSGlobal-D-25-00236).
Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.
References
Literature references
Published research articles and sources related to Pinealon.
- 01Biogerontology (Springer) — Peptide bioregulation of aging: 35‑year research overview by Khavinson and Anisimov View Source
- 02Advances in Gerontology (Springer) — Peptide bioregulators as geroprotectors: experimental studies review View Source
- 03Rejuvenation Research — Pinealon increases cell viability by suppressing ROS and activating proliferation View Source
- 04Biotech Peptides Research Review — Pinealon mechanism of action: direct DNA interaction and gene regulation View Source
- 05LIVV Natural Medical Review — Pinealon in neurological disorders: clinical applications and protocols View Source
- 06Innerbody Research — Pinealon peptide: comprehensive review of benefits, safety, and clinical use View Source
- 07Paragon Sports Medicine — Pinealon peptide: brain health, memory, and cognitive enhancement research View Source
- 08Core Peptides Research — Pinealon effects on neuroprotection, cell vitality, and aging processes View Source
- 09PMC (PubMed Central) — Pinealon protects rat offspring from prenatal hyperhomocysteinemia and cognitive deficits View Source
- 10Doklady Biological Sciences — Regulatory peptides protect brain neurons from hypoxia in vivo View Source
- 11PubMed — Effects of synthetic peptides in patients with chronic polymorbidity and organic brain syndrome View Source
- 12Advances in Gerontology (Springer) — Effects of peptides on behavior and caspase‑3 activity in brain after carotid artery occlusion View Source
- 13Peptide Sciences Research — Pinealon research: reduction of caspase‑3 and free radical damage View Source
- 14Recess Rx Clinical Reference — Pinealon: dosing, mechanism, neuroprotection, and clinical considerations View Source
- 15Advances in Gerontology — Clinical efficacy of peptide bioregulators: comprehensive review and safety profile View Source
- 16PMC (Subcutaneous Drug Injection Review) — Pharmacologic considerations of the subcutaneous route View Source
- 17CDC — Vaccine administration: subcutaneous route (angle/site; no aspiration) View Source
- 18CDC (Subcut Injection PDF) — Technique diagram and site guidance for subcutaneous injections View Source
- 19NCBI Bookshelf — Best practices for injection (asepsis, preparation, and administration) View Source
- 20Pure Lab Peptides — Pinealon (20 mg) product page (quality and batch documentation) View Source
Observed Effects
Observed effects in cited research
Most commonly reported
- Mild headache, especially early in a cycle.
- Sleep changes (vivid dreams, lighter or deeper sleep) during the first week.
- Mild gastrointestinal effects with oral capsules.
- Injection-site redness or itching with subcutaneous use.
Theoretical or under-studied
- Allergic reaction (any peptide can cause one).
- Long-term effects of repeated cycles have not been mapped in published Western trials.
- Pinealon's effect on caspase-3 signaling means cancer-related risk has not been ruled out in or out — researchers in oncology contexts generally exclude it.
Quality-control risks
- Because Pinealon is sold under research-use-only labels, batch purity, sequence identity, and contamination depend on the supplier. Match the certificate of analysis (COA) to the exact vial and lot before any use. Treat poorly documented vials as the bigger near-term risk, not the peptide itself.
Research Considerations
Research considerations
Research Use Only - not for human or veterinary therapeutic use. Current evidence is limited to in vitro and/or animal-model research; human data are minimal or absent. Consult a licensed healthcare professional for any clinical decisions.
- Pregnancy and breastfeeding: safety has not been established. Avoid.
- Active cancer or recent cancer history: Pinealon affects apoptosis and caspase-3 signaling. Because caspase-3 has been linked to both tumor suppression and, in some contexts, tumor support, this group should avoid Pinealon outside formal oncology research.
- Seizure disorders: any compound that acts on the central nervous system should be approached cautiously here.
- Children and teenagers: no safety data exists in this group.
- Anyone on prescription central nervous system medications: drug interactions are not formally mapped.
- Known peptide allergies: prior reactions to any short peptide are a reason to skip it.
Factors noted in the research literature; not patient-specific medical advice.
Regulatory Status
Regulatory status
RUO
Comparisons
Comparisons
| Compound | Mechanism | Route | Status |
|---|---|---|---|
| Pinealonthis | A synthetic tripeptide bioregulator (Glu-Asp-Arg) studied for cell-penetrating, gene-regulatory activity in neural tissue, with proposed antioxidant and neuroprotective effects. | subcutaneous | Investigational / RUO |
| Selank | Modulates GABA and serotonin systems. Increases BDNF. Provides anxiolytic effects without sedation or cognitive impairment. | nasal, subcutaneous | Investigational / RUO |
| Semax | Increases BDNF expression, enhances dopamine and serotonin metabolism. Provides neuroprotection and cognitive enhancement. | nasal, subcutaneous | Investigational / RUO |
| Cerebrolysin | A porcine brain-derived preparation of low-molecular-weight neuropeptides and free amino acids studied for neurotrophic activity supporting neuronal survival, synaptic plasticity, and modulation of neuroinflammation. | subcutaneous | Investigational / RUO |
| DSIP | A naturally occurring nonapeptide studied for influence on sleep architecture and hypothalamic-pituitary-adrenal (stress-axis) modulation; its precise receptor targets remain incompletely characterized. | subcutaneous | Investigational / RUO |
| PNC-27 | A synthetic peptide combining an HDM-2-binding domain with a membrane-penetrating sequence, studied for selective membrane disruption of cancer cells displaying surface HDM-2. | subcutaneous | Investigational / RUO |
| Prostamax | A synthetic tetrapeptide bioregulator (Lys-Glu-Asp-Pro) derived from prostate peptide-complex research, studied for tissue-specific regulatory effects on prostate tissue. | intramuscular | Investigational / RUO |
Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.
FAQ
Frequently asked questions
Pinealon is a synthetic three-amino-acid peptide with the sequence Glu-Asp-Arg, also called the EDR peptide. It was developed by Vladimir Khavinson's research group at the St. Petersburg Institute of Bioregulation and Gerontology in Russia and is studied for neuroprotection, cognition, and cellular stress endpoints.
No. As of June 2026, Pinealon has no FDA-approved indication and is not on the FDA Category 1 (permissible for compounding) bulk drug substance list under sections 503A or 503B. It is sold under research-use-only labeling outside Russia.
Published Russian-language reports used 20 mg per day orally for 10–20 days. Research community protocols for subcutaneous use commonly start around 1.0–2.0 mg per day from a reconstituted 20 mg vial. This is research-context structure, not a dosing recommendation.
Yes — oral capsules at around 20 mg per day are the route used in most published human reports from the Khavinson group. Researchers have proposed that the small tripeptide may use the PEPT2 transporter to cross intestinal and blood-brain barriers, but exact human bioavailability has not been precisely quantified.
A common research approach is to add 3.0 mL of bacteriostatic water to a 20 mg lyophilized vial, giving roughly 6.67 mg/mL. On a U-100 insulin syringe, 1 unit then equals about 66.7 mcg of Pinealon. Always swirl, do not shake, and refrigerate after mixing.
Published cycles run 10 to 20 days, sometimes extended to 28 days, and are usually repeated 2 to 3 times per year. The off-period between cycles is typically 2 to 3 months in the Khavinson group's reports.
For a subcutaneous 10–20 day cycle from a 20 mg vial: 1–2 vials, one fresh U-100 insulin syringe per day, one 10 mL bottle of bacteriostatic water, and a 100-count box of alcohol swabs. See the supplies section above for exact math by cycle length.
Most published research describes Pinealon as well tolerated. Reported effects include mild headache early in a cycle, sleep changes, mild gastrointestinal effects with oral use, and injection-site redness with subcutaneous use. Long-term safety data in humans is limited.
Pregnant or breastfeeding people, anyone with active cancer or a recent cancer history, anyone with a seizure disorder, children and teenagers, and anyone on prescription central nervous system medications should avoid Pinealon outside formal medical supervision.
Both come from Khavinson's research group, but Pinealon is a tripeptide (Glu-Asp-Arg) focused on neuroprotection and cognition, while Epitalon is a tetrapeptide (Ala-Glu-Asp-Gly) focused on pineal gland, telomerase, and longevity endpoints. They are not interchangeable.
Yes, but in small, mostly Russian-language reports. The best-known is a 72-patient study using oral Pinealon alongside standard therapy in adults with consequences of traumatic brain injury. No large Western randomized controlled trial of Pinealon has been published.
No. This page is an educational research-context reference. Pinealon is not FDA-approved for any human use. Talk to a qualified clinician before considering any peptide.
Research-use notice
Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.