Cognitive & Mood

Pinealon

Glu-Asp-Arg (EDR peptide)

Pinealon is a synthetic tripeptide (Glu-Asp-Arg) studied for neuroprotective and cognitive effects. It may support neuronal gene expression and antioxidant defenses, with most evidence from animal and cell models.

Pinealon

Glu-Asp-Arg (EDR peptide)
Cognitive Peptide
Research Only

Half-Life

Not established

Route

Subcutaneous / intranasal

Typical Dose

50 to 200 mcg SC or 100 to 500 mcg intranasal daily

Mechanism / Target

DNA/histone binding and gene expression regulation

Evidence Level

Animal and in vitro

Primary Research Use

Cognitive support and neuroprotection

Mechanism: Pinealon binds DNA and histones to shift gene expression toward neuroprotection, antioxidant defense, and synaptic maintenance.

This information is for research only. Not intended for human use.

Overview

Pinealon is the synthetic tripeptide Glu-Asp-Arg (EDR peptide), developed within the Russian peptide bioregulator program as a minimal active sequence derived from pineal peptide preparations . It is studied mainly for neuroprotection and cognitive effects, not as an acute receptor activator .

A tripeptide means it is made of just three amino acids. Most Pinealon research comes from cell models and animal studies, with only limited human reporting . The strongest preclinical findings involve neuronal survival, dendrite structure, and antioxidant activity .

Research uses span age-related cognitive decline, Alzheimer's disease, Huntington's disease, diabetic cognitive impairment, and stress-related hypothalamic dysregulation .

How it works

Pinealon's primary action is transcriptional rather than acute receptor activation. It can enter the cell nucleus, bind DNA and histone proteins, and shift gene expression toward neuroprotection, antioxidant defense, and synaptic maintenance .

In biophysical work, EDR binds the DNA major groove with preference for guanine N7 and O6 atoms, and magnesium promotes the interaction . Downstream, the peptide is proposed to influence MAPK/ERK signaling and the expression of proteins linked to cell survival, antioxidant enzymes, serotonin, and calmodulin .

Secondary mechanisms from animal and cell data:

  • Antioxidant and hypoxic defense: protects brain neurons from hypoxia in vivo and reduces oxidative DNA damage in human induced neurons .
  • Synaptic plasticity: improves learning and changes NMDA receptor subunit gene expression in diabetic rats .
  • Neuroendocrine regulation: corrects disrupted diurnal hypothalamic norepinephrine dynamics in female rats . In aged primates, the short pineal peptides Epithalamin/Epitalon normalized melatonin/cortisol rhythms , while Pinealon improved cognitive function and restored neuroimmunoendocrine balance .

Documented effects

Pinealon's documented effects are mostly preclinical, with stronger mechanistic support than human efficacy data.

  • Cell models: increased dendritic processes and dendrite length in induced neurons from aged donors, plus reduced oxidative DNA damage .
  • Huntington's disease model: restored dendritic spine morphology in striatal neurons .
  • Diabetic cognitive impairment: improved learning and altered hippocampal NMDA receptor subunit expression in rats .
  • Stress-related circadian disruption: normalized hypothalamic norepinephrine daily rhythms in rats .
  • Aged primates: course administration was associated with improved cognitive function and restored neuroimmunoendocrine balance .
  • Human data: limited to review-level statements of memory improvement in elderly patients, with low methodological clarity .

Research protocols

No human randomized controlled trial defines a Pinealon dose. The strongest evidence comes from rodent, primate, and cell models, often with course-based parenteral administration and unstandardized doses .

Community and practitioner protocols generally describe 50 to 200 mcg subcutaneous or 100 to 500 mcg intranasal once daily for 10 to 20 days, followed by a rest period. Some protocols use 5 days on and 2 days off over 6 to 8 weeks. No formal dose-response curve has been established.

Timing is not standardized. Because animal data show Pinealon normalizes diurnal norepinephrine rhythms , community practice tends toward morning or early afternoon administration. The interactive timeline below shows one representative course pattern, not an evidence-based prescription.

Studied protocol

PinealonCognitive support / neuroprotection · Subcutaneous
1

Active course

100 mcgOnce daily10 days

Practitioner protocols use 50 to 200 mcg subcutaneous once daily.

2

Reset period

NoneNot applicable2 to 4 weeks

Course-based use is commonly followed by an off period.

This information is for research only. Not intended for human use.

Reconstitution and storage

No Pinealon-specific reconstitution studies exist. Standard aseptic handling for lyophilized peptides is used in community protocols.

Use bacteriostatic water for multi-dose vials and sterile water for injection for single-use supplies. Add diluent slowly down the vial wall and swirl gently, rather than shaking, to avoid foaming.

Storage guidance:

  • Lyophilized powder: store at -20°C for long term or 2 to 8°C for short term, protected from light and moisture.
  • After reconstitution: keep at 2 to 8°C; do not refreeze.
  • With bacteriostatic water: discard after 14 days.
  • With sterile water: discard after 24 to 48 hours.

Use the calculator below to determine specific volume and concentration for a given vial and dose.

mg
ml
mcg
Concentration
50 mcg per unit
Doses per vial
100

100 mcg = 2 units · 0.02 ml

2 units on a U-100 syringe

This information is for research only. Not intended for human use.

Open the full Pinealon calculator

Interactions

No formal human drug interaction studies exist. All known interactions are inferred from Pinealon's preclinical mechanisms: DNA/histone binding , modulation of p53, caspase-3, PPAR, serotonin and calmodulin , neuronal NMDA receptor expression , and norepinephrine normalization .

Potential interactions by class:

  • Cognition drugs such as cholinesterase inhibitors and memantine may add to pro-cognitive effects, though no dose-adjustment data exist .
  • Serotonergic drugs including SSRIs, SNRIs, 5-HTP, and St. John's Wort carry a theoretical pharmacodynamic interaction through serotonin and calmodulin signaling .
  • Blood pressure medicines could interact because Pinealon normalizes hypothalamic norepinephrine patterns .
  • Antidiabetic agents have unknown interaction risk; diabetic rat data show NMDA expression changes and learning improvement, but no human glucose data .
  • DNA-damaging treatments: EDR interacts with the DNA major groove and modulates p53 and caspase-3, so caution is appropriate with active chemotherapy or radiotherapy .

Cycling and tolerance

Pinealon is usually cycled as a course rather than taken continuously. Community protocols commonly use 10 to 20 days on, followed by 2 to 4 weeks off. Some protocols use 5 days on and 2 days off for 6 to 8 weeks, then a 4-week break. No randomized controlled trial defines an optimal cycle.

The rationale is transcriptional. Because Pinealon may regulate gene expression through DNA/histone interactions, its cellular effects may outlast plasma clearance, so continuous daily use is not assumed to be necessary . Animal research also uses course-based administration rather than continuous dosing .

No formal tolerance has been demonstrated, but repeated transcriptional stimulation tends to favor rest periods. If cognitive benefit plateaus or side effects such as headache or sleep fragmentation appear, research monitoring guides often suggest a break of at least 2 weeks before reinitiating.

Stacking

Pinealon is commonly discussed alongside other short peptide bioregulators, especially Epithalon. Epithalon is Ala-Glu-Asp-Gly (AEDG), a different peptide with pineal and antioxidant research emphasis, while Pinealon is Glu-Asp-Arg . No head-to-head data exist.

Other combinations from community protocols:

  • Semax / Selank: different mechanisms; no formal interaction data, but sometimes combined for nootropic effects.
  • Cerebrolysin / Cortexin: neurotrophic peptides that may overlap with Pinealon's gene-regulatory and antioxidant effects .
  • BPC-157 / TB-500: no shared pathways identified; some community stacks include them for tissue healing.
  • Growth hormone secretagogues such as CJC-1295 or ipamorelin: no known direct interaction, but blood pressure may deserve monitoring due to Pinealon's norepinephrine-normalizing effect .

Regulatory status

No FDA or EMA approval is identified in the reviewed corpus . Pinealon is not listed in the Controlled Substances Act and is not a DEA-scheduled substance. It is primarily available through research chemical vendors and peptide clinics, not as an approved drug.

In sports, Pinealon is not explicitly named on the WADA Prohibited List in the reviewed sources. However, because it lacks regulatory approval as a human therapeutic, WADA's S0 category for non-approved substances applies. This means Pinealon is prohibited at all times for athletes under WADA Code compliance.

International status is similar: no EMA, TGA, or MHRA marketing authorization is documented.

Safety and side effects

Pinealon has no formal human adverse-event database. Preclinical and limited human reports have not identified serious adverse events at tested microgram doses . Community reports rarely describe transient injection-site redness or stinging after subcutaneous use, and mild nasal irritation after intranasal use.

Because Pinealon binds DNA grooves and histones, theoretical risks include:

  • Epigenetic drift: long-term repeated exposure could alter gene regulation, but no human carcinogenicity or mutagenicity data exist .
  • Cancer interaction: DNA binding and modulation of p53 and caspase-3 raise caution for use in active malignancy or with DNA-damaging therapies .
  • Seizure threshold: NMDA receptor subunit changes in diabetic rats make excitability a theoretical concern, though no seizures were reported.
  • Pregnancy and lactation: no reproductive safety studies exist, so use is generally avoided.
  • Autoimmune conditions and severe kidney or liver impairment: unstudied peptide clearance and potential immune or gene modulation warrant caution.

Frequently asked questions

What is Pinealon and what is the evidence for its use?+

Pinealon is the synthetic tripeptide Glu-Asp-Arg (EDR). Mechanistic data show it partially penetrates the DNA major groove at guanine N7/O6, and review-level evidence proposes downstream regulation of MAPK/ERK, caspase-3/p53, and antioxidant enzymes SOD2/GPX1. In Huntington’s disease mice, EDR restored striatal dendritic spine morphology; in elderly donor-derived induced neurons, EDR reduced oxidative DNA damage and increased dendritogenesis. In non-human primates, course administration improved cognition and neuroimmunoendocrine balance. Evidence level: preclinical (animal/in vitro); no controlled human trial identified.

Is Pinealon FDA-approved?+

No. The reviewed literature describes preclinical research only; no FDA-approved indication exists.

What dose is typically used?+

No human dose-finding trial was identified. Primate and rodent studies report course administration but not standardized human doses. Community protocols generally use 50–200 mcg/day subcutaneous or 100–500 mcg/day intranasal for 10–20 days, then an equal off-period (community protocol). No data support exceeding 200 mcg/day subcutaneous or 500 mcg/day intranasal.

Is subcutaneous or oral better?+

No human pharmacokinetic or route-comparison data exist. Pinealon is a small tripeptide with direct DNA-binding activity; community practice favors intranasal or subcutaneous dosing to avoid first-pass degradation (community protocol). Oral bioavailability is not established.

Can I use Pinealon while pregnant or breastfeeding?+

No human reproductive safety data exist. Available studies are in rodents, non-human primates, and cell models. Avoid use during pregnancy and lactation (practitioner consensus).

How long can I take Pinealon?+

Long-term human safety is unknown. Animal/primate studies used intermittent courses. Community protocols typically use 10–20 day cycles with equal-length breaks; continuous daily use lacks evidence (community protocol).

How does Pinealon compare to Epitalon?+

Pinealon is Glu-Asp-Arg, while Epitalon is Ala-Glu-Asp-Gly (AEDG). Both appear in Russian peptide bioregulator research; Epitalon is linked to pineal/melatonin and antioxidant effects, whereas Pinealon studies emphasize DNA binding, NMDA receptor gene expression, and cognitive/neuroprotective effects. No head-to-head comparative data exist.

Does Pinealon need refrigeration?+

No compound-specific stability data were found. Standard peptide handling: store lyophilized product refrigerated or frozen; keep reconstituted Pinealon at 2–8°C and use within 14–30 days; avoid repeated freeze-thaw cycles (community protocol).

References

  1. 1.Effects of short peptides on the molecular mechanisms of aging in laboratory primatesTrofimova, et al. · 2025
  2. 2.Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related ChangesKraskovskaya, et al. · 2024
  3. 3.EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's DiseaseKhavinson, et al. · 2020
  4. 4.Neuroprotective Effect of EDR Peptide in Mouse Model of Huntington's DiseaseKhavinson, et al. · 2017
  5. 5.Effect of Pinealon on Learning and Expression of NMDA Receptor Subunit Genes in the Hippocampus of Rats with Experimental DiabetesKarantysh, et al. · 2020
  6. 6.Pinealon corrects hyperhomocysteinemia-induced disturbances of the diurnal dynamics of hypothalamic norepinephrine content in female ratsKorenevskii, et al. · 2014
  7. 7.Role of Mono- and Divalent Ions in Peptide Glu-Asp-Arg-DNA InteractionSilanteva, et al. · 2019
  8. 8.Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNAL. I. Fedoreyeva, et al. · 2011
  9. 9.Regulatory peptides protect brain neurons from hypoxia in vivoL. Kozina, et al. · 2008
  10. 10.[Investigation of antihypoxic properties of short peptides]L. Kozina · 2008

Last reviewed on Aug 22, 2026

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