Pinealon is a synthetic Khavinson bioregulator tripeptide, Glu-Asp-Arg (EDR), about 418 Da. It is not FDA-approved. It is not a GLP-1, GIP, or amylin drug. Treatment evidence is almost entirely preclinical: cells and rodents. Nearly all indexed primary work comes from Vladimir Khavinson's St. Petersburg bioregulator network or close collaborators. That single-network concentration is a limit on the map, not a footnote.
A ClinicalTrials.gov search for Pinealon, Glu-Asp-Arg, and EDR peptide returned no registered interventional trial. Russian open-label reports are not Western-style RCTs. DNA-binding and gene-switch claims are hypotheses from biophysics and reviews.
The site already has a short research profile. This explainer is the evidence map that page does not carry. This is the 10:07 Research Roundup, not an incretin story. The Huberman Lab peptides episode is one reason the name is searched in English. Huberman's REM-sleep note is one person's tracked experience, not a finding in the papers used here.
What Pinealon is
PubChem CID 10273502 lists Glu-Asp-Arg as C15H26N6O8, 418.40 Da, CAS 175175-23-2, with pinealon among the synonyms. Kraskovskaya et al. (International Journal of Molecular Sciences, 22 October 2024, PMID 39518916, PMC11546785) give the same formula without counterion. Khavinson, Ribakova, Boldyrev, and colleagues (Rejuvenation Research, October 2011, PMID 21978084) call the synthetic tripeptide pinealon (Glu-Asp-Arg).
The 2020 Molecules review (PMID 33396470, PMC7795577) describes EDR as isolated from Cortexin, a mixed polypeptide from animal brain tissue. Huberman and Bakri made the naming point that matters for search: Pinealon is cortex-associated, not pineal-derived. Epitalon is the pineal bioregulator in that family.
Pinealon is not Humanin or FOXO4-DRI.
| Thing | What it is | What a paper can show |
|---|---|---|
| Pinealon / EDR | Synthetic Glu-Asp-Arg, about 418 Da | Culture ROS and viability, rodent behavior, DNA-contact physics |
| Cortexin | Mixed polypeptide extract from animal cortex | Parent-complex context, not isolated EDR |
| Epitalon | A different Khavinson tetrapeptide (AEDG) | A separate map |
| Research-vendor vial | A catalog chemical sold as Pinealon | Paperwork, not a trial product |
A COA check can test whether a certificate names a real lab. It cannot turn a catalog vial into the 2011 reagent. Pinealon is not approved for human use.
What the studies actually tested
Four primary experimental papers plus one 2024 culture paper define the public map. The 2020 Molecules article is a review, not a new trial.
Khavinson et al., Rejuvenation Research, 2011 (PMID 21978084, DOI 10.1089/rej.2011.1172). In vitro. Authors at the Saint-Petersburg Institute of Bioregulation and Gerontology, with Boldyrev. Synthetic pinealon showed dose-dependent restriction of reactive oxygen species in cerebellar granule cells, neutrophils, and PC12 cells after receptor-dependent or receptor-independent oxidative stress. Necrotic death by propidium iodide fell. The protective effect came with delayed ERK 1/2 activation and a cell-cycle change. ROS and mortality effects saturated at lower concentrations. Cell-cycle modulation continued at higher ones. From that split the authors concluded that pinealon can interact directly with the cell genome, beyond antioxidant activity. That last clause is their interpretation of a dish result. It is not an established mainstream mechanism.
Arutjunyan et al., International Journal of Clinical and Experimental Medicine, 2012 (PMID 22567179, PMC3342713). In vivo rat developmental model, same Khavinson/Arutjunyan line. Pregnant rats received methionine in drinking water at 1 ± 0.01 g/kg body weight per day, which raised maternal plasma homocysteine to 33.0 ± 3.9 μM from 5.9 ± 1.8 μM. Pinealon (Garmonika) in 0.9% NaCl was given intraperitoneally at 10 μg/kg daily for 5 days before methionine loading. Offspring plasma homocysteine at 45 days stayed high in both methionine groups: 9.8 ± 0.2 μM without pinealon and 10.5 ± 0.2 μM with pinealon, versus 5.6 ± 0.6 μM in controls (n = 4 to 5). Pinealon did not correct the homocysteine number.
The cognitive readout was a Morris water maze in 45-day-old pups, n = 23 per arm. First-trial platform search was 112 seconds in intact pups, 170 seconds after prenatal methionine (p < 0.01), and 137 seconds after methionine plus pinealon (p < 0.05 versus methionine and versus control). Later trials narrowed. By the fifth trial the groups met. Cerebellar granule cells from 10-day-old pups were then challenged with 5 mM hydrogen peroxide. After that challenge, mean DCF fluorescence was 158.7 ± 3.8 arbitrary units in the methionine arm and 108.6 ± 4.1 with prenatal pinealon. Necrotic cells were 17.7 ± 2.1% versus 7.0 ± 0.9%. Those are offspring-neuron cytometric numbers after a maternal schedule. They are not a human result.
Mendzheritskii, Karantysh, and Ivonina, Advances in Gerontology, 2011 (PMID 21809624). Russian-language animal paper. Old rats received short peptides before carotid-artery occlusion. The English abstract reports that Pinealon and Cortexin raised survival after modeled occlusion. Under Pinealon, behavioral sleep increased and exploratory, motivational, and motor performance fell. Caspase-3 "moderately raises" in sham-operated animals and in the occlusion model. That is not a simple anti-apoptotic claim. This article uses only the PubMed abstract.
Silanteva et al., Journal of Physical Chemistry B, 7 March 2019 (PMID 30762356, DOI 10.1021/acs.jpcb.8b10359). Biophysics, not efficacy. Authors at the Faculty of Physics, Saint Petersburg State University. Khavinson is not an author. Spectral methods, NMR, viscosimetry, and molecular dynamics were used on Glu-Asp-Arg with DNA. The peptide can partly enter the major groove and affect base atoms, mainly N7 and O6 of guanine. Mg2+ can promote the contact by screening DNA phosphates, including in salted solution. A groove contact in a test tube is not gene switching in a human neuron.
Kraskovskaya, Linkova, Ryzhak, and colleagues, International Journal of Molecular Sciences, 22 October 2024 (PMID 39518916, PMC11546785). Title confirmed: "Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes." EDR, KED, and AEDG were added at 10 μg/mL daily for 10 days to induced cortical neurons from elderly-donor fibroblasts. All three peptides increased dendritic arborization. For EDR, primary processes rose to 5.87 ± 0.5 and total dendrite length to 395.9 ± 43. EDR reduced 8-OHdG by 23% to 0.31 ± 0.03; the authors also report p = 0.0566 as close to significant. Mitochondria, lysosomes, and p16 did not move. Several authors are at the St. Petersburg Institute. Donors were not treated with Pinealon.
Khavinson et al., Molecules, 2020 (PMID 33396470). Review, not a new trial. The authors assume EDR can enter cells and bind histone proteins or RNA, then change MAPK/ERK, caspase-3, p53, SOD2, GPX1, PPARA, PPARG, serotonin, and calmodulin. They cite earlier Russian reports of oral Pinealon plus standard therapy in 72 patients with traumatic-brain-injury consequences. That description is review-level, not a randomized, blinded, placebo-controlled trial.
Open-label human context, not RCTs. Meshchaninov et al., Advances in Gerontology, 2015 (PMID 26390612): 32 people (18 men, 12 women), ages 41 to 83, polymorbidity and organic brain syndrome in remission, given Pinealon and Vesugen. The English abstract reports anabolic and CNS changes, slower biological-age indicators, prooxidant chemiluminescence, and lower CD34+ counts. The authors call the peptides geroprotectors. That is their recommendation, not an efficacy RCT. Umnov, Lin'kova, and Khavinson, Advances in Gerontology, 2013 (PMID 24738258), is a Russian review. A review is context, not a new trial.
| Paper | Design | Human Pinealon as a drug |
|---|---|---|
| Khavinson 2011, Rejuvenation Res | Cerebellar granule cells, neutrophils, PC12 | None |
| Arutjunyan 2012, Int J Clin Exp Med | Pregnant rats, methionine load, offspring maze and cells | None |
| Mendzheritskii 2011, Adv Gerontol | Old rats, carotid occlusion (abstract) | None |
| Silanteva 2019, J Phys Chem B | EDR-DNA spectroscopy, NMR, MD | None |
| Kraskovskaya 2024, Int J Mol Sci | Elderly-donor fibroblast-derived induced neurons | None. Peptide stayed in the dish. |
| Khavinson 2020, Molecules | Mechanism review; cites a 72-patient TBI series | Review-cited Russian reports, not an RCT |
| Meshchaninov 2015, Adv Gerontol | Open-label Pinealon plus Vesugen, n = 32 | Open-label, not an RCT |
A registered interventional human efficacy trial of this synthetic tripeptide was not identified in the evidence review for this article.
Mechanism claims versus limits
The Khavinson reviews treat EDR as a nuclear peptide that contacts DNA or histones and retunes neuroprotective genes. Silanteva 2019 is the physical paper for a DNA contact: major-groove approach and guanine N7/O6, helped by magnesium. That is solution biophysics.
Khavinson 2011 used a different argument. Lower concentrations limited ROS and necrosis. Higher concentrations still moved the cell cycle. The authors treated that split as a genomic interaction. Delayed ERK 1/2 after oxidative challenge is the kinetic observation underneath.
None of those results establish a gene-switch drug. There is no independent ChIP-seq, crystal structure, or Western-style interventional transcriptomic package in this source set. Mendzheritskii's abstract, where caspase-3 rose after Pinealon in sham and occluded old rats, already shows that caspase language does not travel in one direction.
Research doses reported in animals and culture
Pinealon is not approved for human use. The table reports laboratory exposures. It is not a dosage guide or a consumer protocol.
| Setting | Reported exposure | Source |
|---|---|---|
| Cerebellar granule cells, neutrophils, PC12 | Dose-dependent ROS restriction; mortality saturated at lower concentrations than cell-cycle effects | Khavinson et al., 2011 |
| Pregnant rats, before methionine load | 10 μg/kg intraperitoneal daily for 5 days | Arutjunyan et al., 2012 |
| Methionine challenge (context, not the peptide) | 1 ± 0.01 g/kg/day in drinking water | Arutjunyan et al., 2012 |
| Offspring cerebellar cells, stress challenge | 5 mM hydrogen peroxide for 30 minutes | Arutjunyan et al., 2012 |
| Induced neurons from elderly-donor fibroblasts | 10 μg/mL EDR daily for 10 days | Kraskovskaya et al., 2024 |
| EDR-DNA biophysics | In-solution peptide-DNA contact; Mg2+ present in the ion study | Silanteva et al., 2019 |
That does not make 10 μg/kg an approved dose. It also does not make 10 μg/mL or 5 mM hydrogen peroxide an approved dose. Rat intraperitoneal micrograms-per-kilogram are not a human milligram conversion. No anecdotal human-equivalent translation appears here. The Arutjunyan vehicle was 0.9% NaCl, a study vehicle, not a reconstitution protocol. Mendzheritskii 2011 and Meshchaninov 2015 do not contribute milligram figures because the fetched abstracts do not state them.
What this does not mean
- It is not human efficacy. No identified trial gave this synthetic tripeptide to people in a completed Western-style RCT and measured a clinical endpoint.
- It is not an approved cognitive, TBI, Alzheimer's, or anti-aging drug. FDA has not approved Pinealon for any indication.
- It is not Epitalon. Cortex-associated EDR is not the pineal tetrapeptide.
- A 33-second faster first maze trial in rat pups is not a human memory result. Arutjunyan's first-trial gap is 170 versus 137 seconds, n = 23, and it closed by trial five. Offspring homocysteine did not fall.
- Lower ROS in dishes or prenatally exposed cerebellar cells is not a human antioxidant therapy.
- A DNA major-groove contact is not proof that Pinealon switches Alzheimer's genes in people.
- The Molecules review's 72-patient TBI description is not an RCT. Meshchaninov 2015 is 32 people, open-label, with a prooxidant chemiluminescence signal.
- Kraskovskaya 2024 treated induced neurons in a dish. Elderly donors were not dosed.
- A research-vendor listing is not the study product.
- This is not medical advice, and it is not a consumer dosing protocol.
- This is not an incretin story.
Related maps stay on their own molecules: Humanin and FOXO4-DRI.
Limitations
Pinealon's unapproved status did not change on 8 September 2026. The thin research profile was not rewritten. Live listings remain catalog chemicals, not a trial product. Nobody in the primary experimental papers received Pinealon as an investigational drug in a controlled trial. Khavinson 2011, Arutjunyan 2012, the 2020 review, and Kraskovskaya 2024 share the St. Petersburg Institute line or close collaborators. Silanteva 2019 changes the department. Mendzheritskii 2011 changes the senior authors. Both still sit in the same Russian short-peptide literature.
Mendzheritskii 2011, Meshchaninov 2015, and Umnov 2013 are Russian. This article reports their PubMed abstracts and does not invent methods tables. Arutjunyan used 23 pups per maze arm and 4 to 5 animals for offspring homocysteine. Meshchaninov's abstract reports prooxidant chemiluminescence and fewer CD34+ cells. That is not a toxicology program. Catalog strength and salt form are not established by a 2011 dish paper.
What to watch
- A first registered interventional human protocol. Until one exists, Pinealon stays preclinical plus non-RCT Russian reports.
- Independent in-vivo replication that does not share the Khavinson author list. The prenatal-homocysteine and carotid-occlusion phenotypes still need that test.
- Peer-reviewed human pharmacokinetics after a defined lot. No such package is in this source set.
- Whether later papers keep 10 μg/kg intraperitoneal or the 10 μg/mL culture schedule. Those are the two numerical exposures named above.
- A DNA-binding claim that goes beyond groove chemistry. Silanteva 2019 is contact physics, not chromatin occupancy.
- How vendors describe the peptide. Cortexin history and Molecules 2020 language are not a sterility claim. Check whether a certificate names Glu-Asp-Arg.
FAQs
What is Pinealon?
A synthetic Glu-Asp-Arg tripeptide (EDR), about 418 Da, from the Khavinson bioregulator tradition. It is investigational and not FDA-approved. It is not Epitalon.
Has Pinealon been tested in a Western-style RCT?
No completed randomized, blinded, placebo-controlled trial was identified. ClinicalTrials.gov had no Pinealon, Glu-Asp-Arg, or EDR-peptide interventional record in the search used here.
Did it treat Alzheimer's disease, TBI, or aging in people?
No. Primary experimental papers treated cells and rats. The 72-patient TBI description sits in a 2020 review. Meshchaninov 2015 is an open-label series of 32 people given Pinealon and Vesugen.
What dose was used?
Arutjunyan 2012 reported 10 μg/kg intraperitoneal daily for 5 days in pregnant rats. Kraskovskaya 2024 reported 10 μg/mL for 10 days in induced neurons. Pinealon is not approved for human use. That does not make 10 μg/kg or 10 μg/mL an approved dose.
Is Pinealon the same as Epitalon?
No. Pinealon is EDR and cortex-associated. Epitalon is AEDG and pineal-associated. Huberman and Bakri made that naming correction. It is not a shared efficacy claim.
This article is for general informational purposes only and is not medical advice. Talk to a licensed clinician about personal medical decisions. Pinealon is an investigational synthetic tripeptide studied in cells, rats, and non-RCT Russian reports. Nothing here is a dosing protocol or a recommendation to obtain an unapproved product.
Continue your research
- Pinealon listings
- Pinealon research profile
- Humanin
- FOXO4-DRI
- ARA-290
- Huberman peptides episode
- COA Authenticity Checker
Sources
- Khavinson et al. Rejuvenation Res. 2011;14(5):535-541. PMID 21978084
- Arutjunyan et al. Int J Clin Exp Med. 2012;5(2):179-185. PMID 22567179
- Mendzheritskii et al. Adv Gerontol. 2011;24(1):74-79. PMID 21809624
- Silanteva et al. J Phys Chem B. 2019;123(9):1896-1902. PMID 30762356
- Khavinson et al. Molecules. 2020;26(1):159. PMID 33396470
- Kraskovskaya et al. Int J Mol Sci. 2024;25(21):11363. PMID 39518916
- Meshchaninov et al. Adv Gerontol. 2015;28(1):62-67. PMID 26390612
- Umnov et al. Adv Gerontol. 2013;26(4):671-678. PMID 24738258
- PubChem CID 10273502. Glu-Asp-Arg / pinealon. CAS 175175-23-2
- ClinicalTrials.gov search for Pinealon (no interventional hits in this review)