A seven-amino-acid piece of spadin, the fragment released when the protein sortilin is processed. It blocks the TREK-1 potassium channel and produced antidepressant-like behavior in mice within about 4 days; with spadin itself, blocking TREK-1 made serotonin neurons fire faster.
Evidence. Mouse data only, almost all from one French laboratory. No human study of PE-22-28 or of its parent peptide spadin has been published or registered, and no company has taken either into a trial.
Status
Approval
Not approved as a drug anywhere, and never studied in people. No investigational application for PE-22-28 or spadin appears on the public record, and neither is registered on ClinicalTrials.gov.
US compounding
Not nominated for either of FDA’s compounding bulk-substance lists, so it appears in no category, Category 1 or Category 2, for 503A or 503B.
Sport (WADA 2026)
Likely banned in sportNot named on the 2026 list, and potassium-channel blockers are not a listed class. S0 applies: no governmental health authority anywhere approves a medicine containing it, so it is banned at all times.
Category 2 is FDA’s list of bulk substances that may present significant safety risks in compounding. The 503A bulks list adds substances that pharmacies may compound with. Advisory committee votes are advice; FDA makes the final decision. Sport status follows the WADA Prohibited List in force since January 1, 2026; athletes should confirm with their anti-doping organization. Checked October 5, 2026. Status of every compound.
How it works
PE-22-28 blocks TREK-1, a potassium channel that acts as a brake on nerve cells; in cells carrying the human channel it did so at far lower concentrations than spadin, its parent peptide. In mice it reduced depression-like behavior and boosted new nerve cell growth in the hippocampus, a memory area, within 4 days. In spadin’s mouse studies, blocking TREK-1 made serotonin nerve cells fire faster.
AnimalMainly from cell and animal studies; not shown in people.
Not known
No study has given it to a person, so it isn’t known whether it reaches the human brain after injection or nasal spray, what amount would matter, or what long-term TREK-1 blockade does.
Protocol
Community
50–600 mcg once daily, by injection under the skin or as a nasal spray. Guides disagree widely: some put the usual amount at 50–200 mcg, others at 250–400 mcg. No human dose has been tested.
Frequency
Once daily
Route
Subcutaneous injection or nasal spray (community); mice were dosed into the abdomen or by stomach tube
Timing
Morning, in most guides, because evening doses are anecdotally linked to lighter sleep.
Cycle
No established cycle. Guides run 2–6 weeks and then take about 4 weeks off.
Week 15913172125
No set cycle, shown over 26 weeks
Common protocols
The ways PE-22-28 is most often run, each tagged with where it comes from.
Daily injection
Community
Dose
50–200 mcg in some guides, 250–400 mcg in others
How often
Once daily, in the morning
How long
2–6 weeks, then about 4 weeks off
The most described route. The two dose bands don’t overlap, and neither comes from a human study.
Nasal spray
Community
Dose
Roughly 100–500 mcg daily
How often
Once daily
How long
2–6 weeks
Used by people who would rather not inject, and to match Selank and Semax nasal routines. How much is absorbed in people is unknown.
Mouse experiments
Animal
Dose
3–4 mcg/kg into the abdomen, or 1 mg/kg by stomach tube
How often
Single dose, or once daily for 4 days
How long
Up to 4 days
Listed because every community figure is scaled from it. These are animal doses and say nothing about a safe or useful human amount.
Taking it
Where it goes
Community use is an injection under the skin of the belly or thigh, rotating sites, or a nasal spray. The published work injected mice into the abdomen or gave the peptide by stomach tube.
If you miss a dose
No published guidance. Skip the missed dose and resume the next day; don’t double up.
What to expect
Day 1–4
The claimed selling point is speed: in mice, behavior changed after 4 days of once-daily dosing, against 3–4 weeks for an SSRI. No equivalent has been measured in people.
Community
Weeks 1–2
Users describe lifted mood or drive, and some describe nothing. There is no trial to compare against.
Community
Weeks 2–6
Guides stop here and take a break, because no data of any kind cover longer use.
Community
Side effects and what to do
No human side effect profile exists
There is no Phase 1 study, so the list below is only what users report. Absence of reports is not evidence of safety.
Restlessness, anxiety or lighter sleep
Reported at the higher amounts and with evening doses. Lower the amount or dose earlier.
Nasal burning or dryness (nasal route)
Split the dose between nostrils, or stop.
Injection-site redness or soreness
Rotate sites and use sterile technique. Spreading redness, heat or pus needs medical care.
Allergic reaction, possible with any injected peptide
Stop and get emergency care for hives, facial swelling or trouble breathing.
Stop and get medical help
Stop and get medical help for hives, swelling of the face or throat, trouble breathing, a seizure, chest pain or palpitations, or a hot, spreading injection site with fever. Thoughts of self-harm need urgent medical help, not a change of peptide.
Who should avoid it
No product label covers PE-22-28, so these come from human studies and from precautions based on how it works. Most important first.
Epilepsy or a history of seizures
PrecautionMice lacking TREK-1 have seizures more easily. Spadin, its parent peptide, didn’t change seizures in mice, but no human study exists.
Anyone taking antidepressants or other serotonin drugs
PrecautionBlocking TREK-1 made serotonin nerve cells fire faster in mice. Combining it with antidepressants, triptans (migraine drugs) or MAO inhibitors has never been tested.
Heart rhythm problems
PrecautionTREK-1 is also found in the heart. Spadin didn’t change heart function, heart rate or blood pressure in mice, but no study has checked this in people.
Pregnancy or breastfeeding
PrecautionNo human safety data exist.
Anyone relying on product quality
PrecautionIt isn’t an approved drug anywhere, so vials have no regulated standard for identity, purity or sterility.
Interactions
No interaction studies have been published, and no product label lists any.
Precaution: follows from how it works or from a related drug, and hasn’t been tested. This isn’t a complete list: a pharmacist or doctor can check a specific medicine or condition.
Paired for mood in the same stacks. Untested together, and both lack human data for this use.
Human studies
No published human studies of PE-22-28 turned up in our October 2026 review. The evidence note at the top of this page sums up what is known.
Limits of the evidence
PE-22-28 has never been given to a person. Its evidence is a handful of mouse and cell studies, almost all from one French laboratory, using doses per kilogram injected into the abdomen or given by stomach tube. Human absorption, dosing, side effects, interactions and long-term safety are untested, and research vials have no regulated standard for purity.
Mixing your vial
Vial
Water
Common dose
Draw
Strength
Action
5 mg
2 mL
–
–
2.5 mg/mL
10 mg
3 mL
–
–
3.333 mg/mL
Bacteriostatic water. A 10 mg vial in 3 mL gives about 3.3 mg/mL, which makes amounts under 100 mcg hard to measure even on a 0.3 mL syringe; guides that use 50–100 mcg usually mix more thinly.
There’s no established per-injection amount for PE-22-28, so the table shows strength only.
Datasheet
Half-life
No reliable value has been published.
Type
Peptide, 7 amino acids
Molecular weight
773.9 g/mol
Formula
C35H55N11O9
Sequence
GVSWGLR
Storage before use
Freezer (about −20 °C) for long-term storage, dry and away from light.
After mixing or opening
Fridge (2–8 °C); use within about 4 weeks.
Molecule: PubChem CID 165437303 (PE 22-28, CAS 1801959-12-5), free acid. Vials are often supplied as the acetate salt, which weighs more.
Storage:Community Common research-peptide practice; no approved label or manufacturer stability data exists
Never tested in a person. Nothing is known about human absorption, dose, side effects or whether it even reaches the brain.
Every published dose is per kilogram in mice (3–4 mcg/kg into the abdomen, 1 mg/kg by stomach tube). Scaling those to a human amount is guesswork.
TREK-1 is also present in the heart and in circuits that affect seizure threshold. Mouse work found no heart or seizure problems, but no human safety study exists.
Blocking TREK-1 has looked protective in some brain-injury models and harmful in others, so the effect of long blockade is unsettled even in animals.
Stacking it with antidepressants, triptans or MAOIs has never been studied.
Questions
What is PE-22-28?
A seven-amino-acid piece of spadin, the fragment released when the protein sortilin is processed. It blocks the TREK-1 potassium channel and produced antidepressant-like behavior in mice within about 4 days; with spadin itself, blocking TREK-1 made serotonin neurons fire faster.
How does PE-22-28 work?
PE-22-28 blocks TREK-1, a potassium channel that acts as a brake on nerve cells; in cells carrying the human channel it did so at far lower concentrations than spadin, its parent peptide. In mice it reduced depression-like behavior and boosted new nerve cell growth in the hippocampus, a memory area, within 4 days. In spadin’s mouse studies, blocking TREK-1 made serotonin nerve cells fire faster. No study has given it to a person, so it isn’t known whether it reaches the human brain after injection or nasal spray, what amount would matter, or what long-term TREK-1 blockade does.
Is PE-22-28 FDA-approved?
Not approved as a drug anywhere, and never studied in people. No investigational application for PE-22-28 or spadin appears on the public record, and neither is registered on ClinicalTrials.gov. Not nominated for either of FDA’s compounding bulk-substance lists, so it appears in no category, Category 1 or Category 2, for 503A or 503B.
What is the usual PE-22-28 dose?
From community reports, not established: 50–600 mcg once daily, by injection under the skin or as a nasal spray. Guides disagree widely: some put the usual amount at 50–200 mcg, others at 250–400 mcg. No human dose has been tested. These are the amounts sources reference, not recommendations.
Who should avoid PE-22-28?
No product label covers PE-22-28, so these come from human studies and from precautions based on how it works. Epilepsy or a history of seizures: Mice lacking TREK-1 have seizures more easily. Spadin, its parent peptide, didn’t change seizures in mice, but no human study exists. Anyone taking antidepressants or other serotonin drugs: Blocking TREK-1 made serotonin nerve cells fire faster in mice. Combining it with antidepressants, triptans (migraine drugs) or MAO inhibitors has never been tested. Heart rhythm problems: TREK-1 is also found in the heart. Spadin didn’t change heart function, heart rate or blood pressure in mice, but no study has checked this in people. The “Who should avoid it” section lists 2 more groups.
How should PE-22-28 be stored?
Before mixing: Freezer (about −20 °C) for long-term storage, dry and away from light. After mixing: Fridge (2–8 °C); use within about 4 weeks. This is common practice; no product label covers it.
Is PE-22-28 banned in sport?
Probably. Not named on the 2026 list, and potassium-channel blockers are not a listed class. S0 applies: no governmental health authority anywhere approves a medicine containing it, so it is banned at all times.
Has PE-22-28 been studied in people?
No published human studies turned up in our October 2026 review. The evidence note at the top of this page sums up what is known.
Sources
Djillani et al., shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity (Front Pharmacol 2017) — mouse study PMID 28955242
Mazella et al., spadin, a sortilin-derived peptide targeting rodent TREK-1 channels (PLoS Biol 2010) — mouse study PMID 20405001
Djillani et al., fighting against depression with TREK-1 blockers: past and future, a focus on spadin (Pharmacol Ther 2019) — review PMID 30291907
For how it works, who should avoid it and the limits of the evidence
Moha Ou Maati et al., spadin and TREK-1-related side effects in mice (Neuropharmacology 2012) PMID 21807005
Heurteaux et al., TREK-1 knockout mice, seizures and ischemia (EMBO J 2004) PMID 15175651
Doses tagged Community come from public dosing guides and user reports, checked against at least two of them. Those sites aren’t named here because many of them sell peptides or earn commissions on them.