Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-26. ← Back to Evidence Library

PE-22-28 (mini-spadin): what the evidence says

Name: PE-22-28 (mini-spadin)
Creator: Dr. Nova Reyes
Published: 2026-10-26

At a glance

What it is: a lab-made 7-amino-acid peptide, a shortened version of spadin, a fragment of the sortilin propeptide. It blocks the TREK-1 potassium channel in nerve cells. Made by Jean Mazella's group in France. ^{R1, R2}

What the evidence says: in mice it acted like a fast antidepressant, worked at very low concentrations in cells, lasted longer than spadin and boosted new nerve cells after 4 days. ^R1 A related short form helped mice recover after stroke. ^R3 No human study exists.

Biggest risks: unknown in people. Blocking TREK-1 might in theory raise seizure, pain or stroke sensitivity; spadin did not show these in mice. ^R4

Rating


Human Human evidence	None
Animal Animal / lab evidence	Mouse depression models, stroke model, human TREK-1 cells ^{R1, R3, R2, R5}
Regulatory	Never approved · Not on FDA 503A or 503B bulk lists · WADA 2026: not named; likely S0 Caution ^{R6, R7, R8}
Established human dose	None. Study details lists what studies used

Evidence verdict: Depression or mood in people: No human data · Antidepressant-like effects: Animal only (mice) Card verdict: No human data (antidepressant & stroke claims rest on mouse studies only) Card note: Mouse data only, see page

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: nearly all spadin and PE-22-28 work comes from one French academic group (CNRS, Sophia Antipolis) and its collaborators. ^{R2, R1, R9}

What is it?

Mice without TREK-1 resist depression-like behavior, so blocking it became an antidepressant target. Spadin is a natural 17-amino-acid blocker; PE-22-28 is a 7-amino-acid piece. Related pages: Semax, Selank, Dihexa.

Does it work?

Animal Djillani 2017: blocked human TREK-1 in cells about 300–500 times more strongly than spadin; reduced despair behavior in the forced swim test; cut feeding latency after 4 days; boosted new nerve cells and synapses; effect lasted up to 23 hours vs 7 for spadin. ^R1
Animal Stroke (Moha ou Maati 2019): mini-spadin helped recovery and reduced post-stroke depression signs in mice. ^R3
Animal Spadin: worked in 4 days in mice vs about 21 for standard antidepressants. ^{R2, R4}
Unknown No human study.

Is it safe?

Animal Spadin did not cause the pain, seizure or stroke sensitivity seen in TREK-1-deleted mice. ^R4
Unknown No safety data for PE-22-28 beyond mouse behavior studies.

Gray-market "research use only" PE-22-28: extra risks

A gray-market vial has no quality control and no guarantee of identity, strength or sterility. We test retail vials blind under the Open Peptide Standard; see /tests/. A passing test covers one batch on one date and does not mean the compound is safe. Gray-market products are often nasal sprays; no published study tested this route.

What we don't know

Unknown Any effect in people with depression
Unknown Safety, including heart rhythm and seizure risk

Is it legal?

US (FDA): never approved. Not on the 503A or 503B bulk lists, so there is no compounding route. ^{R6, R7}
Athletes: not named on the WADA 2026 list. UNVERIFIED likely covered by S0. ^R8

Study details

These are amounts researchers used, not recommendations. | Study | People / model | Route | Amount used | Follow-up | Reported | Citation | |---|---|---|---|---|---|---| | Djillani 2017 | Mice; human TREK-1 cells | Injection Caution route | Caution not in abstract; cell IC50 0.12 nM | Up to 4 days | Antidepressant-like effects | [PMID 28955242](https://pubmed.ncbi.nlm.nih.gov/28955242/) | | Mini-spadin stroke 2019 | Mice | Intraperitoneal | 0.03 µg/kg once a day for 7 days | Weeks Caution | Better recovery | [PMID 31325429](https://pubmed.ncbi.nlm.nih.gov/31325429/) |

Full reference list (PubMed, CT.gov, FDA and WADA checked Oct 26, 2026)

^R1 Djillani A, et al. Front Pharmacol. 2017. PMID 28955242
^R2 Mazella J, et al. PLoS Biol. 2010. PMID 20405001
^R3 Pietri M, et al. Neuropharmacology. 2019. PMID 31325429
^R4 Moha Ou Maati H, et al. Neuropharmacology. 2012. PMID 21807005
^R5 Veyssiere J, et al. Psychopharmacology (Berl). 2015. PMID 25080852
^R6 FDA, 503A bulk drug substances categories list (updated May 14, 2026). https://www.fda.gov/media/94155/download
^R7 FDA, 503B bulk drug substances categories list (updated Mar 21, 2025). https://www.fda.gov/media/94164/download
^R8 WADA. The 2026 Prohibited List, S0. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
^R9 Djillani A, et al. Pharmacol Ther. 2019. PMID 30291907

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use PE-22-28 (mini-spadin). Talk to a clinician you trust, especially if you have depression, take psychiatric medicines, have a seizure or stroke history, or are pregnant. Do not stop prescribed antidepressants. Report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).