Pinealon
EDR Peptide (L-Glutamyl-L-Aspartyl-L-Arginine)
A synthetic neuroprotective tripeptide (Glu-Asp-Arg) with limited human and multiple preclinical evidence for reducing oxidative stress and apoptosis in neurons, including MAPK/ERK modulation, caspase-3 regulation, and antioxidant enzyme upregulation (PMID 21978084, PMID 33396470, PMID 22567179).
Last updated: 2026-03-09
Safety Summary
Pinealon has a very low reported side effect profile across both the Russian clinical literature and community reports. Accessible peer-reviewed abstracts did not provide systematic adverse-event tables. The human study of 32 patients (PMID 26390612) noted prooxidant activity by chemiluminescence and decreased CD34+ hematopoietic cells, which warrant monitoring but did not produce clinical adverse events in that study. The study used combined Pinealon + Vesugen so attribution to Pinealon alone is uncertain. Community reports in online communities describe minimal side effects, typically limited to mild fatigue if dosed during daytime. In vitro, EDR did not demonstrate direct antioxidant activity but restricted lipid peroxidation by modifying lipoprotein structure, and elevated intracellular ROS while simultaneously decreasing cell death (PMID 18546826), suggesting a complex hormetic mechanism. No systematic safety monitoring has been conducted.
Known Side Effects
uncommon
uncommon
rare
uncommon
rare
Who Should NOT Use This
No reproductive safety data available. Pinealon's effects on gene expression and neural development make it unsuitable for use during pregnancy without safety studies. No formal contraindication studies have been conducted.
Pinealon modulates cell proliferation and the cell cycle (PMID 21978084). Effects on tumor biology are unknown and could theoretically be detrimental. No formal contraindication studies have been conducted.
The 32-patient human study found significant inhibition of hematopoiesis (decreased CD34+ hematopoietic stem cells) during combined Pinealon and Vesugen treatment (PMID 26390612). Clinical significance unclear and attribution to Pinealon alone uncertain, but warrants caution in patients with pre-existing hematopoietic conditions.
Talk to Your Doctor
Before considering Pinealon, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-16]
Evidence Assessment
Tier 3: Multiple small human studies exist alongside strong preclinical support. Human evidence includes: (1) 72 TBI patients with oral Pinealon showing improved memory and cognitive function (cited in PMID 33396470, original Russian publications); (2) 32 patients aged 41-83 with organic brain syndrome showing improved CNS activity and biological aging markers with Pinealon + Vesugen (PMID 26390612); (3) locomotive brigade workers showing improved biological age and adaptation parameters after 2 weeks of oral Pinealon (PMID 22708445); (4) 150 lorry-drivers and 150 metal craftsmen with improved psychoemotional indices from bioregulating peptides including Pinealon + Vesugen (PMID 23734521). None were randomized controlled trials. Several used Pinealon combined with Vesugen, making attribution difficult. All research originates from the Khavinson group or collaborators with no independent Western replication. The human literature is mostly Russian-language, often poorly detailed in accessible abstracts, and sometimes confounded by co-treatment. No ClinicalTrials.gov entries exist for Pinealon. Preclinical evidence is more robust, including multiple in vitro and animal studies on neuroprotection, antioxidant enzyme upregulation, and anti-apoptotic effects (PMID 21978084, PMID 22567179, PMID 33396470).
1Pinealon increases cell viability by suppression of free radical levels and activating proliferative processesPMID 21978084
Khavinson V et al. - Rejuvenation Research (2011) - in vitro - Cerebellar granule cells, neutrophils, PC12 cells
Pinealon demonstrated dose-dependent ROS suppression in multiple cell types under receptor-dependent and receptor-independent oxidative stress. Reduced necrotic cell death by propidium iodide test. Delayed ERK1/2 activation time course and modified cell cycle. Effects saturated at lower concentrations for ROS/cell death, while cell cycle modulation continued at higher concentrations, suggesting direct genome interaction.
Limitations: In vitro only. Single research group. No quantitative dose-response data reported in abstract.
2Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNAPMID 22117547
Fedoreyeva LI et al. - Biochemistry (Moscow) (2011) - in vitro - HeLa cells and in vitro nucleic-acid systems
Fluorescence-labeled Pinealon entered cytoplasm, nucleus, and nucleolus of HeLa cells. Showed sequence-selective interactions with DNA and oligonucleotides, especially CNG and CAG-containing sequences. Peptides discriminate between different nucleotide sequences and recognize cytosine methylation status.
Limitations: In vitro only. Binding data do not prove therapeutic gene regulation in living humans. Single research group.
3Pinealon protects the rat offspring from prenatal hyperhomocysteinemiaPMID 22567179
Arutjunyan A et al. - International Journal of Clinical and Experimental Medicine (2012) - animal study - Rat offspring from methionine-loaded pregnant dams
Pinealon improved offspring spatial orientation and learning ability. Decreased ROS accumulation and necrotic cell counts in cerebellar neurons after prenatal hyperhomocysteinemia. Protected against neurodevelopmental consequences of elevated homocysteine during gestation.
Limitations: Animal model only. Single research group. Full text not in English; details from abstract and secondary sources.
4Investigation of antihypoxic properties of short peptidesPMID 18546825
Not specified in source abstract - Russian-language journal (2008) - animal study - Rats (hypobaric hypoxia model)
Among four short peptides tested (vilon, epitalon, vesugen, pinealon), Pinealon showed the most pronounced antihypoxic properties. Mechanism based on stimulation of internal antioxidant enzyme system and possibly limiting excitotoxic effect of NMDA, rather than direct ROS inhibition.
Limitations: Russian abstract only. No detailed methods or effect sizes. Single research group.
5Biological activity of regulatory peptides in model experiments in vitroPMID 18546826
Not specified in source abstract - Russian-language journal (2008) - in vitro - Human lipoproteins, red blood cells, neuronal populations
Pinealon and related short peptides did NOT demonstrate direct antioxidant activity but restricted lipid peroxidation by modifying lipoprotein structure. Increased red blood cell membrane stability against osmotic hemolysis. Elevated intracellular ROS levels while simultaneously decreasing cell death in neuronal populations, suggesting hormetic/regulatory mechanism.
Limitations: In vitro only. Paradoxical ROS increase with decreased cell death needs further investigation. Russian-language. Single research group.
6Effects of introduction of short peptides before carotid artery occlusion on behaviour and caspase-3 activity in the brain of old ratsPMID 21809624
Not specified in source abstract - Russian-language journal (2011) - animal study - Old rats with carotid artery occlusion model
Pinealon pretreatment increased survival after carotid occlusion. Increased behavioral sleep time and reduced position-finding, motivational, and motor behavior. Caspase-3 activity moderately increased in both sham-operated and occluded animals given Pinealon.
Limitations: Animal model of cerebral ischemia. Russian-language. Exact sample sizes not reported. Caspase-3 increase interpretation clinically ambiguous. Single research group.
7Regulation of content of cytokines in blood serum and of caspase-3 activity in brains of old rats in model of sharp hypoxic hypoxia with Cortexin and PinealonPMID 25051764
Mendzheritskii AM et al. - Advances in Gerontology (Uspekhi Gerontologii) (2014) - animal study - Old rats (number not specified in abstract)
In acute hypoxic hypoxia, Pinealon promoted neurogenesis increase and decreased neuroinflammatory reactions (IL-6, TNF) to reference levels. Cortexin reduced programmed cell death but maintained high IL-6 levels. Different neuroprotective profiles for the two peptides.
Limitations: Animal study. Russian-language. Sample size not specified. Result wording is interpretive; abstract does not give numeric cytokine changes. Single research group.
8Effect of peptide geroprotectors on the navigation system learning and caspase-3 in brain structures in rats of different agePMID 28976148
Not specified in source abstract - Russian-language journal (2013) - animal study - Young and old rats
Pinealon had a preferential positive effect on learning in Morris water maze in both young and old animals compared to Cortexin. Regional changes in caspase-3 activity identified in cerebral cortex and brainstem.
Limitations: Animal study. Russian-language. Exact sample sizes not reported. No full quantitative learning data in accessible source text. Single research group.
9Pinealon and Cortexin influence on behavior and neurochemical processes in 18-month aged rats within hypoxia and hypothermiaPMID 28509493
Not specified in source abstract - Russian-language journal (2015) - animal study - 18-month-old rats
In acute hypobaric hypoxia and mild hypothermia stress models, Cortexin showed more pronounced effects on free radical processes and caspase-3 than Pinealon. Both peptides promoted adrenergic mediator accumulation in brain under hypoxia and serotonin accumulation in cerebral cortex under hypothermia.
Limitations: Animal study. Russian-language. Limited detail in English abstract. Single research group.
10Analysis of some parameters of biological age and adaptation possibilities of workers of locomotive brigadesPMID 22708445
Not specified in source abstract - Russian-language journal (2012) - open-label human study - Locomotive brigade workers (exact N not specified in abstract)
Workers received Pinealon capsules (100 mcg, 2 times daily for 2 weeks). Improved parameters of biological age and indicators determining effectiveness of adaptive reactions.
Limitations: Open-label, no reported control group. Sample size not specified. Russian-language. Short treatment (2 weeks). Occupational population may not generalize. Single research group.
11The peptide correction of neurotic disorders among professional truck-driversPMID 23734521
Not specified in source abstract - Russian-language journal (2012) - human study - 150 male lorry-drivers and 150 male metal craftsmen
Bioregulating peptides improved psychoemotional indices, resistance to work stress, and reduced occupational risk of borderline mental disorders (p < 0.001-0.05). The best effect was obtained with combined Pinealon and Vesugen.
Limitations: Pinealon was not isolated as a stand-alone intervention; combined with Vesugen. Occupation-specific population. Intervention design details limited in abstract. Russian-language.
12Effect of synthetic peptides on aging of patients with chronic polymorbidity and organic brain syndrome of the central nervous system in remissionPMID 26390612
Not specified in source abstract - Russian-language journal (2015) - open-label human study - 32 patients (18 men, 14 women), ages 41-83
Combined Pinealon and Vesugen had significant anabolic effect, improved CNS activity and vital organ function, slowed aging rate by biological age indicators. Vesugen showed stronger geroprotective effect than Pinealon. Found prooxidant activity by chemiluminescence. Decreased CD34+ hematopoietic stem cells. Peptides did not affect chromatin condensation degree.
Limitations: Small sample (N=32). Open-label, no control group. Russian-language. Combined intervention (Pinealon + Vesugen). Prooxidant activity and hematopoiesis inhibition raise safety questions. Single research group.
13EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's DiseasePMID 33396470
Khavinson V et al. - Molecules (2020) - review - N/A (review of published data)
Comprehensive review analyzing EDR peptide effects on AD pathogenesis: MAPK/ERK signaling, caspase-3 and p53 regulation, SOD2 and GPX1 antioxidant enzymes, PPARA and PPARG transcription factors, serotonin synthesis. EDR prevented dendritic spine loss in hippocampal neurons from 5xFAD AD mice. References human data: oral Pinealon in 72 TBI patients improved memory. EDR binding sites identified in promoter regions of CASP3, TP53, SOD2, GPX1, PPARA, PPARG genes.
Limitations: Review by the developer group. Human study data cited from earlier Russian publications not independently available. Mechanistic model involves proposed direct DNA-peptide interaction that remains debated.
14Peptide Regulation of Gene Expression: A Systematic ReviewPMID 34834147
Khavinson V et al. - International Journal of Molecular Sciences (2021) - systematic review - N/A (review)
EDR binds to dsDNA large groove via N7 and O6 atoms of guanine (NMR, viscometry, molecular dynamics). Peptides AEDG, EDR, AEDL, KEDG, AEDR, KEDW bind to histone proteins H1, H2B, H3, H4. EDR binding sites found in promoter regions of AD-related genes. Mg2+ ions enhance EDR-DNA binding.
Limitations: Review by the developer group. DNA-peptide interaction model not independently replicated. Physiological relevance of in vitro binding to in vivo gene regulation not established.
15Neuroprotective effects of peptides bioregulators in people of various agePMID 24738258
Not specified in source abstract - Russian-language journal (2013) - review - N/A (review)
Comparative review of polypeptide complexes (cortexin, cerebrolizin) vs. short peptides (semax, kortagen, pinealon). Summarizes clinical data on peptide use in elderly and old age.
Limitations: Review article. Russian-language. Limited to summarizing existing literature from same research community.
16Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future DirectionsPMID 41490200
Not specified - Journal of the American Academy of Orthopaedic Surgeons (or similar) (2025) - review - N/A (review)
Categorizes Pinealon among sleep and recovery optimization peptides alongside Epithalon and DSIP. Notes Pinealon influences neuronal metabolism, supports mitochondrial function in aging/stressed neural tissue.
Limitations: Review article. Does not present original Pinealon data. Pinealon discussion is brief within a broader peptide review.