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Pinealon3 residuesEDREach bubble = one amino acid. Size = residue mass. Color = chemical class.Also known as: EDR, Glu-Asp-Arg, Pinealon
Three amino acids. Glu-Asp-Arg. That is the entire sequence of Pinealon (EDR), a synthetic tripeptide bioregulator developed by Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. Fluorescence-labeled studies confirmed it reaches cell nuclei, where it interacts with DNA promoter regions tied to melatonin synthesis and neuroprotection. Formal human clinical trials? Zero. But community users running 10 to 20 day courses consistently describe improved sleep onset and circadian rhythm correction, particularly shift workers and adults over 40. The research base is narrow and originates from a single group; the community signal, while small, is directionally consistent.
Twenty-two papers on PubMed as of April 2026, nearly all from one laboratory. That is the evidence base behind Pinealon, also known as EDR (Glu-Asp-Arg, molecular weight 404.4 Da, CAS pending). This synthetic tripeptide belongs to the Khavinson bioregulator family, short peptides designed to reach the nucleus and modulate gene expression in specific tissues. The target tissue here is the pineal gland and broader central nervous system. In cell and animal models, Khavinson's group showed EDR upregulates AANAT (the rate-limiting enzyme in melatonin synthesis) and TPH1 (tryptophan hydroxylase 1, a serotonin synthesis enzyme). It also shifted the Bcl-2/Bax ratio toward cell survival, increased BDNF expression, and activated PGC-1alpha for mitochondrial biogenesis [1]. A 2017 study confirmed EDR restored neuronal spine density in an in vitro Alzheimer's disease model [2]. A 2024 study tracked EDR reducing oxidative DNA damage in aged induced neurons (DOI 10.3390/ijms25211363). Community use is niche. Discussion concentrates on Longecity forums (topics 83250 and 111763), not Reddit. Users run 10 to 30 day subcutaneous courses at 100 to 500 mcg per day, typically in the evening. The most consistent report is improved sleep quality and circadian regularity. Cognitive clarity gets mentioned less often and tends to disappoint users expecting something comparable to Semax. The honest assessment: mechanism is plausible, animal data is consistent, community reports align with the proposed biology. But the entire evidence chain traces back to one group with no independent replication. Treat this as a genuinely experimental compound.
Pinealon (EDR) was originally isolated from Cortexin, a neuroprotective polypeptide drug used in Russian clinical practice. At 404.4 Da, it is small enough to cross the blood-brain barrier and translocate into cell nuclei. Fluorescence-labeled tracking confirmed this nuclear entry [1]. Once inside the nucleus, EDR binds DNA promoter regions and chromatin-associated proteins. The downstream effects mapped so far include upregulation of AANAT, which controls the rate-limiting step of melatonin synthesis. It also increases TPH1 expression, boosting serotonin production upstream of melatonin. This dual pathway modulation explains the circadian rhythm effects users report. Beyond the melatonin axis, EDR shifts the Bcl-2/Bax apoptosis ratio toward cell survival, reducing programmed cell death in stressed neurons. It activates PGC-1alpha, triggering mitochondrial biogenesis. It increases histone acetylation at neuronal gene loci, loosening chromatin structure to allow transcription of neuroprotective genes. BDNF expression goes up. Antioxidant enzymes SOD2 and GPX1 get upregulated through MAPK/ERK signaling. The epigenetic mechanism is the key distinction from direct melatonin supplementation. Pinealon does not supply melatonin; it changes the transcriptional environment so the pineal gland produces more of its own. This is why Khavinson protocols specify short courses with long off-periods. The gene expression changes are proposed to persist after the peptide clears, though that claim lacks controlled human confirmation.
Preclinical-only evidence from a single Russian research group (Khavinson Institute). EDR translocates to cell nuclei, modulates BDNF, Bcl-2/Bax ratio, AANAT, and TPH1 in animal/cell models. No controlled human clinical trials published.
Khavinson et al., "EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease": Molecules 2021, PMID 33396470. Most recent: Khavinson et al., "Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes": Int J Mol Sci 2024, DOI 10.3390/ijms25211363 (EDR reduced oxidative DNA damage in aged induced neurons; promoted dendritic tree development).
All primary research from a single group with known publication bias. Most papers in Russian or translated without independent replication. No pharmacokinetic studies in humans. No RCTs. Epigenetic claims are mechanistically plausible but unconfirmed.
Niche bioregulator with very low Reddit penetration. Users describe subtle effects (sleep quality, circadian restoration, mild cognitive clarity) over 10–20 day cycles. Frequently disappointing for those seeking a measurable nootropic lift.
Science supports circadian/melatonin-pathway modulation via AANAT and TPH1 upregulation. Community sleep and rhythm reports are broadly consistent with that mechanism. Cognitive enhancement claims have weaker scientific backing and limited community verification.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 100mcg | Daily |
| Moderate | 200mcg | Daily |
| Aggressive | 200mcg | Daily |
Start with the math. A 20 mg vial reconstituted with 2 mL bacteriostatic water gives you 10,000 mcg per mL, or 100 mcg per unit on a U100 insulin syringe. So your beginner dose of 100 mcg is 1 unit. Moderate (200 mcg) is 2 units. At 200 mcg per day, one vial lasts 100 days, well beyond a single 10 to 30 day course. Dose in the evening, 1 to 2 hours before sleep. This aligns with the natural melatonin rise and matches the Khavinson protocol. The most common mistake is confusing mcg (injectable) with mg (oral). A 200 mcg subcutaneous dose is not the same as 200 mg oral. Swapping those units creates a greater than 1,000-fold error. Subcutaneous doses are in micrograms. Oral capsule doses are in milligrams. Double-check your units every time. Skip caffeine within 6 hours of your evening dose. Store reconstituted vials at 2 to 8 degrees Celsius and use within 3 weeks.
Standard Russian bioregulator cycling protocol. The long off-period is intended to allow endogenous regulatory mechanisms to re-establish. Limited data on optimal cycling.
The Khavinson bioregulator model specifies short course + extended rest based on the epigenetic mechanism: EDR initiates gene transcription changes that persist after the peptide clears (~2–5 min estimated plasma half-life). Continued daily administration beyond 10–30 days is not thought to add incremental benefit once the transcriptional signal is established. The extended off-period (3–6 months) allows the endogenous system to integrate and stabilize changes before the next induction course. The 4-on/8-off weeks structure in peptides.ts approximates this principle but does not precisely match the Khavinson published protocol (10–30 day courses with 3–6 month gaps).
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Expected: Improved sleep onset, more consistent circadian rhythm. Community reports effects at 2–3 weeks; repeat cycle after off-period if needed.
Monitor: Monitor for vivid dreams (common); headache (rare). No labs required at this dose.
Draw 2 mL of bacteriostatic water into a syringe using a mixing needle (18 to 21 gauge). Inject the water slowly down the inside wall of the vial. Do not shake. Swirl gently until the powder dissolves completely. This gives 10,000 mcg per mL (100 mcg per unit on a U100 syringe).
Draw your dose into an insulin syringe (29 to 31 gauge, U100). Beginner: 1 unit (100 mcg). Moderate: 2 units (200 mcg). Aggressive: 2 units (200 mcg) with option to titrate toward 3 units (300 mcg) during weeks 3 to 4.
Choose an injection site: lower abdomen (1 to 2 inches from the navel), outer thigh, or back of the upper arm. Rotate sites each day.
Pinch a small fold of skin, insert the needle at a 45 to 90 degree angle, inject slowly, hold for 5 seconds, then withdraw. Apply light pressure with an alcohol swab if needed.
Avoid caffeine within 6 hours of your dose.
For oral use: take one 10 mg capsule (or encapsulated lyophilized powder) with a small amount of dietary fat, 1 to 2 hours before sleep. Oral dosing runs 10 to 20 mg per day, reflecting the 20 to 50 times higher dose needed compared to subcutaneous.
Store reconstituted vials at 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit). Use within 3 weeks. Lyophilized (unreconstituted) vials are stable at room temperature for up to 2 months, or refrigerated for up to 2 years.
20–50× higher dose required: 10–20 mg oral vs. 200–500 mcg SC
EDR (~404 Da) survives gastric digestion better than most peptides. Russian Cytogen commercial capsules (10 mg) are the clinical precedent. US research vendors offer lyophilized powder for encapsulation. Take with a small amount of dietary fat; avoid on an empty stomach. Not reflected in peptides.ts dosingTiers: FLAG P2.
Unknown; no published PK for intranasal EDR
Community reports exist but no dosing data or bioavailability estimates are available. Cannot recommend: dose cannot be established.
Most commonly cited bioregulator combination. Epithalon works upstream (telomere maintenance, AANAT normalization); Pinealon works downstream (direct neuroprotection, serotonin/melatonin synthesis support). No interaction concerns in literature or community.
Run simultaneously during the same 10–20 day course, or sequentially (Epithalon first, then Pinealon after 1–2 weeks).
Khavinson cardiovascular bioregulator layered into longevity stacks alongside Pinealon for multi-system coverage. Referenced in Longecity bioregulator experience thread (topic 83250).
Complementary sleep stack. DSIP for acute insomnia (faster onset); Pinealon for chronic circadian dysregulation (slower, epigenetic mechanism). Not typically combined simultaneously: used for different presentations.
Cognitive enhancement pairing. Semax provides acute BDNF boost and working memory effects; Pinealon provides slower neuroprotective background. Community-reported timing: Semax mornings, Pinealon evenings.
Pinealon upregulates TPH1 (tryptophan hydroxylase 1), increasing neuronal serotonin synthesis. Concurrent use with serotonin reuptake inhibitors risks elevated synaptic serotonin. Mechanistically real, not boilerplate.
Do not combineCombined TPH1 upregulation from Pinealon + MAO inhibition blocks serotonin breakdown: serotonin excess risk. Avoid concurrent use.
Do not combineAdditive serotonin precursor load on top of Pinealon TPH1 upregulation. Use with caution or avoid without medical supervision.
Potential additive effects via AANAT pathway modulation. Low physiological doses (0.5 mg) are less concerning; pharmacological doses (5–10 mg) should be avoided during cycle.
Pricing updated 2026-04-09
The serotonin interaction risk is the most serious safety concern with Pinealon. EDR upregulates TPH1, which increases neuronal serotonin synthesis. Combining Pinealon with SSRIs (fluoxetine, sertraline, escitalopram), SNRIs (venlafaxine), or MAO inhibitors (phenelzine, tranylcypromine, selegiline) could elevate synaptic serotonin to dangerous levels. Serotonin syndrome symptoms include agitation, muscle twitching, diaphoresis, and tachycardia. This is not a theoretical warning on paper. The TPH1 mechanism is documented in preclinical data, and concurrent use with serotonergic medications should be avoided or closely supervised by a physician. 5-HTP supplements add to the same serotonergic load and carry the same caution. Melatonin supplements at pharmacological doses (3 mg or higher) may produce additive sedation through the AANAT pathway. Low physiological doses around 0.5 mg are less concerning, but stacking 5 to 10 mg melatonin on top of a Pinealon cycle is not advisable. Vivid dreams are the most commonly reported side effect. They appear in the first 3 to 5 days of a cycle, especially at doses of 200 mcg and above. Most users report normalization by day 7 to 10. This is expected given the melatonin pathway activation and is not a reason to discontinue unless sleep architecture is severely disrupted. Mild headache occurs rarely. Community reports place this in the first week, resolving without intervention. Injection-site reactions are standard for subcutaneous administration. Rotate sites. Use a 29 to 31 gauge needle. The critical limitation: the safety dataset is very small. No controlled human clinical trials have been published. Total published human exposure data across all Khavinson group papers covers a limited number of subjects. No long-term safety monitoring data exists. No pregnancy or breastfeeding safety data exists; avoid use during pregnancy, breastfeeding, and in children or adolescents. When to stop: if agitation, unusual sleep disruption, or muscle twitching appears during a cycle, discontinue immediately. Check for concurrent serotonergic medications. Wait 3 to 5 days before reassessing. If headache or mood changes persist beyond 3 days, discontinue.
Verify Pinealon dosing and safety with a second opinion
No USP-grade or pharmaceutical-standard supplier exists for Western consumers. Russian Cytogen commercial capsules (Khavinson-linked brand) represent the only regulated formulation available. US research vendors are unregulated; purity varies. EDR is a simple, verifiable tripeptide (HPLC + mass spec confirmation is feasible), which reduces but does not eliminate contamination and mislabeling risk.
| Test | When | Target |
|---|---|---|
| Mood / sleep diary (Pittsburgh Sleep Quality Index, PSQI) | Daily during cycle; compare baseline vs. week 2 and end of cycle | — |
| Melatonin levels (serum or first-morning urine) | Optional: baseline before first cycle; repeat at end of cycle if circadian disruption is the primary indication | — |
| Serotonin syndrome symptom check | If co-using any serotonergic drug (SSRI, SNRI, MAOI, 5-HTP) | Clinical assessment: no numeric threshold. Discontinue Pinealon immediately if ≥2 serotonin syndrome criteria met. |
Primary way to gauge response: no biomarker is directly tied to Pinealon activity in humans. PSQI is a validated self-report instrument.
Indirect proxy for AANAT pathway function. Useful in shift workers or confirmed circadian disorder.
TPH1 upregulation adds to serotonergic load. Symptoms: agitation, muscle twitching, diaphoresis, tachycardia.
Some users report improved sleep onset and subjective sleep quality. These early reports are anecdotal and may reflect placebo response.
Possible improvement in circadian rhythm regularity and morning alertness. Still too early for measurable cognitive effects.
Anecdotal reports of enhanced memory and focus. Neuroprotective effects, if real, would be accumulating at the cellular level but are not directly perceptible. End of standard on-cycle.
Bioregulator theory suggests effects persist after discontinuation as gene expression changes stabilize. This claim lacks controlled human data.
Days 1 through 3: Expect very little. EDR is entering cell nuclei and beginning transcriptional changes at AANAT, TPH1, and antioxidant gene loci. No systemic output is measurable yet. Some users report slightly deeper sleep by night 2 or 3, but most notice nothing. Vivid dreams are common on the first few nights. Mild injection-site discomfort if you are new to subcutaneous injections. Days 4 through 14: This is the window where circadian effects start showing up. AANAT and TPH1 gene expression changes accumulate. Users who respond describe improved sleep onset and better consistency in their sleep-wake cycle. Morning alertness gets mentioned. Shift workers describe circadian resynchronization here. Vivid dreams usually settle down. Occasional mild headache. Weeks 2 through 4: Neuroprotective gene expression changes (Bcl-2/Bax, BDNF, SOD2) are accumulating at the cellular level, but there is no direct way to perceive them. A minority of users report subtle cognitive clarity. Mood stability and stress resilience are the more common reports at this stage. Memory improvement is rarely mentioned; if that is your primary goal, expectations should be set realistically. Post-cycle (weeks 5 through 20 off): Bioregulator theory holds that gene expression changes persist after the peptide clears. This is the core premise of Khavinson cycling, but it has not been confirmed in controlled human trials. Some users report sustained sleep quality and mild cognitive benefit lasting 4 to 6 weeks after stopping. Others notice nothing lasting. Distinguishing real persistence from natural regression to the mean is difficult without formal study design.
EDR begins translocating to cell nuclei and initiating transcriptional changes at AANAT, TPH1, and antioxidant loci. No measurable systemic output at this stage.
Some users report slightly improved sleep depth by night 2–3. Most report nothing. Placebo-responsive window.
AANAT and TPH1 gene expression changes accumulating. Melatonin synthesis pathway normalization underway in animal models.
Users who respond report improved sleep onset and consistency. Morning alertness noted. Shift workers describe circadian resynchronization in this window.
Neuroprotective gene expression changes (Bcl-2/Bax, BDNF, SOD2) accumulating. No direct perceptible correlate identified in humans.
Subtle cognitive clarity reported by minority of users. Mood stability and stress resilience most cited at this stage. Memory improvement rarely reported.
Bioregulator theory: gene expression changes persist after peptide clearance. Not confirmed in human controlled trials.
Some users report sustained sleep quality and mild cognitive benefit 4–6 weeks post-cycle. Not universal. Difficult to distinguish from natural regression to mean.
Source: Estimated from tripeptide class pharmacokinetics; no direct PK study for EDR. Small peptides are rapidly cleared (minutes).
Loading the interactive decay curve.
Pinealon (EDR) is classified as a research chemical in the United States. It is not FDA-approved for any indication. It does not appear on the FDA 503A or 503B bulks lists, so no US compounding pathway exists. Purchase is available through research peptide vendors for investigational use only. In Russia, commercial capsule formulations (Cytogen brand, Khavinson-linked) are available as a regulated product. Availability outside Russia is limited and typically involves importation. Pinealon has not been evaluated by WADA for athletic competition. Athletes subject to anti-doping testing should verify status with their governing body before use. No pending regulatory changes have been identified as of April 2026. The March 2026 FDA enforcement action that closed Peptide Sciences did not specifically target Pinealon but reflected broader regulatory tightening across the US research peptide market. This content is for informational and educational purposes only. It does not constitute medical advice. Consult a licensed healthcare provider before using any peptide. Pinealon is an experimental compound with no approved human therapeutic use.
Peptide Schedule Research TeamReviewed Apr 20266 Citations
