Pinealon
A Khavinson-class synthetic tripeptide (Glu-Asp-Arg) targeted at the pineal gland and brain, studied preclinically for neuroprotection, antioxidant defense, and circadian support.
Pinealon is a synthetic tripeptide (glutamyl-aspartyl-arginine, EDR) developed by Vladimir Khavinson's group at the St. Petersburg Institute of Bioregulation and Gerontology as a pineal-gland-derived short bioregulator. It is proposed to enter neurons and modulate gene expression, protecting against oxidative stress and supporting neuronal integrity, circadian regulation, and cognition. Evidence comes almost entirely from Russian-origin preclinical and cell-culture work with minimal independent Western replication and no FDA approval. It is sold as a research-use-only compound and used in the community via pulsed injectable or intranasal cycles.
Class
Synthetic tripeptide (Khavinson short-peptide bioregulator)
Half-life
Minutes in plasma; proposed durable CNS/gene-expression effects are not well quantified
Routes
Subcutaneous, Intranasal, Intramuscular (Russian research), Oral (Cytogen capsules; low bioavailability)
Category
Cognitive & Nootropic
Researched benefits
What it's studied for
Neuroprotection against oxidative stress
In cultured neurons, EDR suppresses reactive oxygen species and necrotic cell death and is proposed to reduce lipid peroxidation and support mitochondrial function. Evidence is preclinical and largely single-lab.
Synapse and dendritic-spine preservation
In an in vitro Alzheimer's model, EDR at 200 ng/ml restored mushroom-shaped dendritic spine density by 71% under amyloid synaptotoxicity, positioning it as a candidate for synapse preservation.
Epigenetic gene-expression modulation
Molecular-modeling work predicts EDR binds histone H1.3 and modifies chromatin at the Fkbp1b locus (a neuronal calcium regulator), proposing an epigenetic mechanism for age-related cognitive preservation.
Cognitive support in aging models
Khavinson-group rodent studies report improved cognitive performance markers and neuroprotection in aged animals and after cerebral ischemia. Human cognitive-enhancement claims are unverified.
Circadian and sleep regulation
As a pineal-targeted bioregulator, Pinealon is proposed to support melatonin-pathway and clock-gene signaling upstream of melatonin itself, with community reports of improved sleep quality. Not clinically established.
Ischemia/stroke-recovery biology
After carotid occlusion in rodent stroke-adjacent research, EDR shows neuroprotective and recovery effects, a mechanism reviewers describe as more specific than generic nootropic marketing.
Mechanism
How it works
Pinealon is a three-amino-acid signaling peptide (Glu-Asp-Arg) built on the Khavinson short-peptide bioregulator theory: differentiated tissues produce short regulatory peptides that carry tissue-specific signals, and synthetic analogs are proposed to reach the corresponding tissue and modulate gene expression there. Pinealon was derived from a bovine pineal extract (Epiphamine), with the EDR sequence identified as the biologically active fragment and then synthesized.
The proposed core mechanism is direct gene-expression regulation. Khavinson-group work argues that small, charged short peptides can cross cell membranes (via peptide transporters or direct permeability), enter the nucleus, and bind specific DNA motifs or histones to modulate transcription. A frequently cited study reported nuclear entry of fluorescently labeled Pinealon and binding to specific DNA sequences in cultured cells, and computational modeling predicts binding to histone H1.3 near the Fkbp1b calcium-regulator gene in hippocampal neurons.
Downstream, Pinealon is claimed to protect neurons against oxidative stress and beta-amyloid toxicity, support mitochondrial function, upregulate neurotrophic factors (BDNF, NGF), and support circadian regulation through pineal-related and melatonin-adjacent pathways without directly binding melatonin receptors. Its small size and charge underpin a theoretical case for blood-brain-barrier penetration.
The honest limitation: cellular-level effects in simple in-vitro systems are reasonably documented, but whole-organism pharmacokinetics, blood-brain-barrier delivery at clinically meaningful doses, and the direct-DNA-binding transcription-factor claim have not been rigorously validated by independent Western labs. Plasma half-life is only minutes, and the claim of prolonged CNS effects from pulsed dosing is not well quantified.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Reconstitution
Supplied as lyophilized powder in 5 mg or 10 mg vials. Reconstitute with bacteriostatic water (30-day refrigerated stability) or sterile water (use within 24-48 h). Inject the water slowly down the vial wall and swirl gently, do not shake. Common dilutions: 2 mL BAC water into a 10 mg vial = 5 mg/mL (500 mcg per 0.1 mL / 5 units); 1 mL into a 10 mg vial = 10 mg/mL. At 5 mg/mL: 2 mg = 0.4 mL (40 units), 3 mg = 0.6 mL (60 units), 5 mg = 1.0 mL (100 units). Store lyophilized powder refrigerated and protected from light; discard reconstituted solution if cloudy, discolored, or older than 30 days.
Beginner
- Dose
- 2-5 mg/day SC (start 2-3 mg); intranasal alternative 150-300 mcg per nostril once daily
- Frequency
- Daily during the cycle
- Timing
- Morning or early afternoon; avoid late evening
- Duration
- 10-20 day cycle, then 60-90 day washout; 2-4 cycles/year
- Route
- Subcutaneous (most common) or intranasal
Run Pinealon alone on the first cycle to gauge response. Effects are subtle and cumulative and may persist for weeks after the course; no obvious effect on the first cycle is common.
Intermediate
- Dose
- 3-7 mg/day SC; or intranasal 300-500 mcg per nostril 1-2x daily
- Frequency
- Daily, sometimes split morning + midday at half-dose
- Timing
- Morning preferred
- Duration
- 15-20 day cycles, roughly quarterly (3-4/year)
- Route
- Subcutaneous or intranasal
Often integrated into a broader longevity/cognitive protocol and paired with other Khavinson peptides (commonly Epithalon). If no response after 2 full cycles, increase toward 7 mg/day or verify product purity before escalating.
Advanced
- Dose
- 5-10 mg/day SC (sometimes split 2.5 mg twice daily); intranasal 500-800 mcg per nostril twice daily
- Frequency
- Daily; some run continuous low-dose intranasal
- Timing
- Morning, or morning + midday if split
- Duration
- 20-30 day cycles, 3-4/year; some run continuous intranasal for 3-6 months
- Route
- Subcutaneous or intranasal
Used within multi-year full Khavinson organ-rotation stacks and with clinical biomarker monitoring. Doubling dose is unlikely to double effect (pulsatile, threshold signaling); do not exceed 10 mg/day without specific justification.
- Pinealon follows a pulsed rather than continuous dosing convention: short daily courses with long washouts, on the theory that peptide pulses trigger durable gene-expression changes persisting beyond the dosing window.
- Do not dose continuously longer than 30 days without a washout; separate cycles by 60-90+ days.
- Morning administration aligns with pineal-melatonin physiology; evening dosing may disrupt sleep.
- Intranasal doses are typically 10-20x lower than subcutaneous doses due to more direct nose-to-brain delivery, though this route is less characterized for Pinealon than for Semax.
- Oral Pinealon is largely degraded by gastric/intestinal proteases and is not recommended for reliable dosing.
- Source from reputable suppliers with a certificate of analysis showing HPLC purity (target >=98%) and a molecular weight matching Glu-Asp-Arg; consumer dosing is not established by any Western regulator.
Evidence
Research & clinical studies (2)
Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's Disease
In primary mouse hippocampal neuron cultures, EDR (Pinealon) at 200 ng/ml increased mushroom-shaped dendritic spine density by 71% under amyloid synaptotoxicity, restoring spine density to normal in this Alzheimer's model.
PMID 28853087Epigenetic Mechanisms of Peptide-Driven Regulation and Neuroprotective Protein FKBP1b
Molecular-modeling work predicts that short peptides including EDR bind histone H1.3, potentially modifying chromatin at the Fkbp1b (calcium regulator) locus in hippocampal neurons, proposing an epigenetic basis for peptide neuroprotection.
PMID 31099784Combinations
Stacking & blends
Cognitive & Longevity Stack
Neuroprotection and anti-aging cognitive support
Pinealon (brain/pineal) is run alongside Epithalon (pineal/telomere) in overlapping or alternating cycles, with intranasal Semax for acute cognitive load and NAD+ plus omega-3/vitamin D/B-complex cofactors as a foundation.
Circadian & Sleep Stack
Circadian rhythm and sleep-quality support
Morning Pinealon supports pineal/clock-gene signaling upstream while low-dose DSIP and melatonin at bedtime address sleep onset and circadian disruption; magnesium glycinate and glycine round it out.
Full Khavinson Bioregulator Rotation
Annual tissue-specific bioregulation across organ systems
Advanced multi-year protocol cycling organ-specific Khavinson peptides month by month (brain, pineal, immune, cartilage, cardiac, etc.); rationale is Khavinson's overall framework rather than head-to-head efficacy data.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Pregnancy and lactation (no developmental data)
- Pediatric use (under 18)
- Known peptide hypersensitivity
- Active seizure disorder without neurologic management
- Active CNS infection or recent severe head trauma
- Active hormone-sensitive cancer or pineal/CNS tumor without oncologic evaluation
- Acute severe psychiatric illness without supervision
- Inability to source verified-purity product or use safe injection technique
Pinealon is generally well tolerated in the available Russian clinical literature and community reports, with mild effects most common, attributed to its short length and proposed non-receptor mechanism. However, long-term human safety is not characterized at Western clinical standards, most data come from a single research group, and rare or delayed effects cannot be ruled out. It is not currently on the WADA prohibited list, though research-chemical contamination can still cause positive tests. Discontinue for any severe allergic reaction, seizure, new/worsening psychiatric or neurologic symptoms, or injection-site infection.
FAQ
Pinealon — common questions
What is Pinealon?
Pinealon is a synthetic tripeptide (Glu-Asp-Arg, EDR) from the Khavinson short-peptide bioregulator family, derived from bovine pineal extract research and positioned as a pineal/brain-targeted neuroprotective and cognitive peptide. It is investigated for neuroprotection, antioxidant defense in the CNS, circadian support, and anti-aging effects in brain tissue.
What does the evidence actually show?
Evidence is preclinical and largely single-lab: in-vitro neuroprotection (ROS suppression, dendritic-spine restoration), rodent ischemia-recovery and aging-cognition data, and epigenetic gene-expression modeling from the Khavinson group. There are essentially no independent Western clinical trials and no confirmed human pharmacokinetics, so cognitive-enhancement claims in humans remain unverified.
How does Pinealon differ from Epithalon?
Both target pineal tissue but differ in sequence and focus: Pinealon is a tripeptide (Glu-Asp-Arg) studied for neuroprotection and cognition, while Epithalon is a tetrapeptide (Ala-Glu-Asp-Gly) studied for telomerase activation and broader anti-aging. They are frequently used together in Khavinson-protocol research.
How is Pinealon dosed?
Community protocols use pulsed cycles: typically 2-10 mg/day subcutaneous (starting 2-3 mg) for 10-30 days, morning-dosed, followed by a 60-90 day washout, at 2-4 cycles per year. An intranasal alternative uses roughly 150-800 mcg per nostril daily. There is no FDA-approved dose.
How does it differ from melatonin?
Melatonin is a hormone that binds MT1/MT2 receptors to directly signal sleep, whereas Pinealon is a peptide proposed to work upstream by supporting the pineal gland's regulatory (gene-expression) function. Melatonin is inexpensive and well-characterized; Pinealon is a research-grade peptide with a much narrower evidence base.
What are the side effects?
Reports are minimal and mild, mainly occasional injection-site reactions and possible sleep disruption if dosed late. No contraindications are firmly established, but long-term human safety data is limited and it should be avoided in pregnancy, hormone-sensitive cancer, and pineal/CNS pathology without specialist oversight.
Is Pinealon FDA approved or legal?
No. Pinealon is not approved by the FDA, EMA, or any major Western regulator and has no active approval pathway. It is sold as a research chemical, legal to purchase for laboratory use in most jurisdictions but not authorized for human consumption in the US, EU, or most Western markets.
Why does vendor verification matter?
The short tripeptide is easy to synthesize and broadly available, but related Khavinson tripeptides can be mislabeled. Independent third-party HPLC purity testing with mass-spectrometry identity confirmation (expected MW around 417-419 Da) is the standard quality check before use.
