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Animal data onlyNot FDA approved

PE-22-28

Also known as: PE 22-28 · PE22-28 · Mini-spadin · GVSWGLR · Gly-Val-Ser-Trp-Gly-Leu-Arg · PE 22-28 acetate

Updated 21 sources

A seven amino acid piece of spadin (residues 22 to 28 of the sortilin propeptide) that blocks the TREK-1 potassium channel. In mice it lifted depression-like behavior and grew new hippocampal cells within 4 days. It has never been dosed in a human study, so every human dose online is community convention.
Calculate with PE-22-28Dosage chart

Quick facts

Half-life
  • Not published. Described as relatively short in serum in vitro; the 23 hour effect half-time often quoted belongs to modified analogs in mice.
Routes
  • Nasal
  • Subcutaneous injection
Forms
  • Vial (powder)
  • Nasal spray
Reported dose ranges
  • 100 to 500 mcg (nasal)
  • 50 to 500 mcg (subcutaneous injection)
Vial sizes
  • 8 mg, 10 mg, 20 mg
Chemistry
  • 773.88 g/mol · C35H55N11O9 · CAS 1801959-12-5
FDA status
  • Not FDA approved
WADA
  • Not confirmed

What people use PE-22-28 for

  • Low mood and depression-like symptoms, hoping for a faster onset than SSRIs
  • Focus, motivation and brain fog, usually at lower doses
  • Stress and anxiety resilience, often stacked with Selank
  • Neuroprotection after stroke or injury, based on one mouse study

How it is thought to work. PE-22-28 blocks TREK-1 (KCNK2), a two-pore potassium channel that quiets neurons. Blocking it raises serotonin neuron firing in mice. It is far more potent than spadin at the channel (IC50 about 0.1 nM vs 40 to 60 nM) and leaves TREK-2, TRAAK, TRESK, TASK-1 and hERG alone. In a stroke model a very low dose activated TREK-1 instead, so its effect flips with dose.

PE-22-28 dosing

8 protocols from studies, guides and community reports, grouped by goal. Tap a source badge to see where a number came from.

Nasal, nasal spray4

Intranasal standard (community)

Amount
200 to 400 mcg
How often
Once daily, in the morning
Route
Nasal, nasal spray
Cycle
4 to 8 weeks, then a break of unfixed length
Timing and details

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Tiered nasal ladder (community)

Amount
100 to 500 mcg
How often
Once each morning, or twice (morning and early afternoon) at the higher tiers
Route
Nasal, nasal spray
Cycle
4, 6 or 8 weeks; or 5 days on, 2 off
Rest
2 to 4 weeks off after 4 weeks, 3 to 4 after 6, 4 after 8
Timing and details

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Intranasal 400 mcg (guide)

Amount
400 mcg
How often
Once daily, in the morning
Route
Nasal, nasal spray
Timing and details

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Clinic range, nasal or subQ

Amount
100 to 500 mcg
How often
Daily
Route
Nasal, nasal spray
Cycle
4 to 12 weeks for a first run
Timing and details

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Injected4

Subcutaneous low dose (community)

Amount
100 to 200 mcg
How often
Once daily, in the morning
Route
SubQ, vial (powder)
Cycle
4 to 8 weeks, then a break
Timing and details

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Slow subcutaneous titration (community)

Amount
100 to 200 mcg
How often
Once daily, starting at 100 mcg and rising to 150 to 200 mcg
Route
SubQ, vial (powder)
Cycle
8 to 16 weeks with gradual titration
Timing and details

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Subcutaneous titration (guide)

Amount
50 to 200 mcg
How often
Once daily, stepping up
Route
SubQ, vial (powder)
Cycle
12 to 16 weeks, 8 weeks minimum
Titration (4 steps) and details

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High twice-daily outlier

Amount
250 to 500 mcg
How often
Twice daily, morning and early afternoon
Route
SubQ, vial (powder)
Rest
4 weeks off
Timing and details

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Doses shown are what sources report, labelled by origin. Not medical advice.

Full PE-22-28 dosage guideEvery titration step in syringe units, missed doses and how to mix.

Vial strengths and syringe units

Every PE-22-28 vial size with the water volumes sources use. Units are what to draw on a U-100 insulin syringe, worked out exactly.
PE-22-28: concentration and U-100 syringe units for each vial size and water volume
WaterStrength50 mcgdose, units100 mcgdose, units200 mcgdose, units
8 mg vial
2 mLCompetitor guide†4 mg/mL1.30.013 mL2.50.025 mL50.05 mL
3 mLCompetitor guide†2.667 mg/mL1.90.019 mL3.80.038 mL7.50.075 mL
5 mLCompetitor guide†1.6 mg/mL3.10.031 mL6.30.063 mL12.50.125 mL
10 mg vial
2 mLCompetitor guide5 mg/mL10.01 mL20.02 mL40.04 mL
3 mLCompetitor guide3.333 mg/mL1.50.015 mL30.03 mL60.06 mL
5 mLCompetitor guide2 mg/mL2.50.025 mL50.05 mL100.1 mL
20 mg vial
3 mLCompetitor guide6.667 mg/mL0.80.008 mLunder 1 unit1.50.015 mL30.03 mL
Units are on a U-100 insulin syringe (100 units = 1 mL). U-50 and U-30 barrels read the same units.† Water volume sourced for a different vial size. The math is exact either way.Water volumes from

Doses shown are what sources report, labelled by origin. Not medical advice.

Calculate with this peptideYour vial, your water, your dose: PE-22-28 in syringe units, with the math shown.

PE-22-28 side effects

What trials and labels report, kept apart from what users and guides report. Frequencies are worded as each source states them.

Reported by users and guides6

From community reports and dosing guides. Not measured rates.

  • Lethargy or sedation

    The most commonly reported complaint, mostly above about 500 to 600 mcg a day

    How people manage it

    • Community reports hold the dose at or under 400 mcg and take it in the morning

  • Nasal irritation

    Reported occasionally with nasal use; a clinic calls it the most common effect of that route, fading within the first week

  • Mild headache

    Occasionally in the first few days, usually settles on its own

  • Mild fatigue early on

    Some report it in the first week

  • Injection-site redness or tenderness

    Occasional, minor

    How people manage it

    • Rotate sites

  • Heart, pain and seizure pathways (theoretical)

    No reports; TREK-1 sits in heart and pain signalling, and mice lacking TREK-1 seize more easily. In mice PE-22-28 left the hERG heart channel alone.

All 6 PE-22-28 side effects and how people manage themEvery management tip, who should not use it, and side-effect questions.

Who should avoid it

  • Prescribed antidepressantsSubstance

    No interaction study exists for PE-22-28 with SSRIs or other antidepressants.

  • Epilepsy or seizure historyCondition

    Mice lacking TREK-1 are more seizure-prone, and PE-22-28 blocks TREK-1. Untested, but the mechanism points this way.

Storage

Powder (before mixing)

Temperature
-20 °C

Freezer at -20 C, dry and dark. Vendors claim up to 24 months, or at least 4 years, at -20 C; one data sheet says 1 year at -20 C or 2 years at -80 C.

Mixed vial

Temperature
2 to 8 °C
Use within
28 days

Fridge at 2 to 8 C, away from light. Guides say use within 28 days or 4 weeks; community reports say 3 to 4 weeks. No PE-22-28 stability study exists.

Mixed with: Bacteriostatic water

Mixing. For a nasal sprayer, work backward from the mcg you want per 0.1 mL spray: at 5 mg/mL one spray is 500 mcg, above the usual range, so nasal users add more water. Swirl, do not shake.

Stacks people report

Combinations from guides and community posts, with the reason given.
  • Selank

    The mood stack: PE-22-28's TREK-1 blockade for mood plus Selank's GABA-linked calming. No interaction data.

  • Semax

    The cognition and mood stack: PE-22-28 for mood and neurogenesis, Semax for focus and BDNF. No interaction data.

Compare PE-22-28

Evidence and legal status

Evidence: animal data only

Animal and cell studies only, all from the group that developed it: mouse antidepressant-like effects and hippocampal neurogenesis after 4 days at 3 to 4 mcg/kg, and protection in a mouse stroke model. No human pharmacokinetic, safety or efficacy study exists.

FDA and WADA

Not FDA approved

No approval, no trial program and not on FDA's compounding lists.

Not FDA approved, and no human trial is registered. PE-22-28 is not named in any of FDA's 503A nominated-substance categories (updated May 14, 2026) or on its compounding safety-risk page. It is sold as a research chemical.

PE-22-28 is not named on the WADA 2026 Prohibited List, and it does not belong to any named class (it is a TREK-1 blocker, not a growth factor or GH secretagogue). The S0 class covers any pharmacological substance without human therapeutic approval, which on its plain wording could include PE-22-28. No source addresses this directly.

WADA: Not confirmed

PE-22-28 questions

What is PE-22-28?

A seven amino acid fragment (GVSWGLR) of PE, the propeptide that also gives rise to spadin. It is the shortest piece that still blocks the TREK-1 potassium channel, and its developers call it mini-spadin.

What is the usual PE-22-28 dose?

Community reports run 200 to 400 mcg by nasal spray, or 100 to 200 mcg by subcutaneous injection, once each morning, with the daily total kept under 600 mcg. None of this comes from a human study.

Nasal spray or injection?

Both are used and nasal is more common in community reports. Neither route has been studied for PE-22-28 in any species; the mouse work used intraperitoneal injection, plus oral gavage at a much higher dose.

How much bacteriostatic water goes in a 10 mg vial?

2 mL is the common choice, giving 5 mg/mL, so 200 mcg is 4 units on a U-100 syringe. One guide uses 3 mL (3.33 mg/mL). For a nasal sprayer at about 0.1 mL per spray, 5 mL gives 200 mcg per spray.

What does PE-22-28 do in studies?

In mice, 3 to 4 mcg/kg cut forced-swim immobility, and a 4-day course reduced feeding latency and roughly doubled new hippocampal cells (1736 vs 899 BrdU-positive cells). It also raised the synapse marker PSD-95 in cultured neurons. These are animal and cell results only.

What dose did the mouse studies use?

3.0 to 4.0 mcg/kg by intraperitoneal injection, as one dose or once daily for 4 days; 1 mg/kg worked by gavage. A stroke study gave 0.03 mcg/kg daily for 7 days, then 3 mcg/kg on 4 days a week. One wiki says 0.1 mg/kg; the primary paper does not.

What is the half-life of PE-22-28?

Not published. The developers describe a relatively short serum half-life in vitro. The often-quoted 23 hours is the half-time of the antidepressant effect in mice for modified analogs (G/A-PE 22-28 and its biotinylated form), not PE-22-28 itself; spadin's was about 6 to 7 hours.

What are the side effects?

Lethargy above roughly 500 to 600 mcg a day is the main community report. Nasal irritation, mild headache and early fatigue also come up. There is no human safety or toxicology data.

Should I take PE-22-28 in the morning or at night?

Morning. Community protocols keep it early in the day because higher doses bring lethargy.

Is PE-22-28 the same as spadin?

No. Spadin is PE 12-28 (17 amino acids); PE-22-28 is the last 7. It blocks TREK-1 at about 0.1 nM against 40 to 60 nM for spadin, and the mice needed 3 to 4 mcg/kg instead of 100 mcg/kg.

How fast does PE-22-28 work?

Mice responded after a 4-day course, against the 2 to 4 weeks SSRIs need in rodent models. Community users report mood changes within days. There is no human timing data.

How long is a PE-22-28 cycle?

Usually 4 to 8 weeks, then a break, in community reports. That habit is borrowed from other peptides; the longest mouse study ran a few weeks.

Has PE-22-28 been tested in humans?

No. ClinicalTrials.gov lists no PE-22-28 studies, and all published work is in mice and cells from the lab that developed it.

Is PE-22-28 FDA approved?

No. It is not approved and does not appear on any of FDA's 503A compounding lists. WADA does not name it either; its S0 catch-all for unapproved substances could apply on plain wording, but no WADA source addresses PE-22-28 directly.

Ask about PE-22-28

Answers come from this site's pages only, with a link to each source.

Sources

21 sources, each checked by date. Record updated Oct 24, 2026. Numbers are restated in our own words and labelled by where they came from.

Vendor guide5

  1. PE-22-28 (8 mg) research briefVendor product page · checked Oct 24, 2026
  2. PE-22-28 10 mg product pageVendor product page · checked Oct 24, 2026
  3. PE-22-28 peptide 2026: benefits, dosage, side effects and protocolinjectco.com (clinic) · checked Oct 24, 2026

Competitor guide7

  1. PE-22-28 reconstitution: 10 mg vial to 5 mg/mLthepeptidecatalog.com · checked Oct 24, 2026
  2. PE-22-28 dosing and scaling research guidepeptidescalculator.com · checked Oct 24, 2026
  3. PE-22-28 (10 mg vial) dosage protocolpeptidedosages.com · checked Oct 24, 2026

Community-reported1

  1. PE-22-28 community protocols and reportspeptideprotocolwiki.com, via a competitor guide · checked Oct 24, 2026