PE 22-28 quick reference
What is PE 22-28?
Seven-amino-acid piece of spadin, a peptide that blocks the TREK-1 channel.
Built to last longer than spadin; tested for mood in mice.
No human study exists.
How PE 22-28 works
Blocks the TREK-1 potassium channel at 0.12 nM in human-channel cells.
Designed from spadin's blood breakdown products; spadin's effect faded after 7 hours.
Four days of treatment raised new-cell growth in mouse hippocampus.
Raised PSD-95 in cultured mouse cortical neurons.
What PE 22-28 is studied for
Mice spent less time immobile in the forced swim test.
Mice ate sooner after 4 days of treatment.
Four-day treatment raised neurogenesis in mice.
Raised PSD-95 in cultured mouse cortical neurons.
IC50 0.12 nM on human TREK-1 in cells; spadin 40–60 nM.
PE 22-28 dosing protocol
| Item | What the sources show |
|---|---|
| Human dose | Not established |
| Studied in | Mice and lab cells |
Mouse treatment lasted 4 days in the novelty feeding test. ClinicalTrials.gov lists no PE 22-28 or spadin trial (searched 5 Nov 2026).
Label and trial amounts come from the sources below. Community amounts are what people report; they have not been tested.
Mixing
Example math only. No human dose exists.
What the research found
No human results exist. Lab and mouse findings:
Front Pharmacol 2017, PMID 28955242 (spadin analogs; PE 22-28 is the 7-amino-acid analog).
PE 22-28 community experience
What users report. Not tested in trials.
Positive reports
- Gentle lift One public thread describes a mild mood lift.
- Subtle, not stimulating Appeal is a quiet shift, not a buzz.
- Novel target Interest comes from a different mechanism than usual nootropics.
Negative & mixed
- Short-lived The same thread calls the benefit small and temporary.
- Hard to judge Too few reports to say how often it works.
- Muddied results Stacks, sleep changes and vial quality blur the picture.
PE 22-28 stacking
Mood plus calmer stress response. Never studied together.
Mood plus focus in theory. Two changes at once hide the cause.
Exploratory pairing. No validated protocol.
PE 22-28 side effects & safety
Common
- No human side-effect data exists.
- Injection-site irritation if injected (community).
- Nasal irritation if sprayed (community).
- Changes in sleep, anxiety or mood: frequency unknown.
Less common
- Agitation or mood swings: rate unknown.
- Long-term brain and heart safety: not studied.
Precautions
- Mania, unstable mood or suicidal thoughts need professional care.
- Avoid in pregnancy, breastfeeding and children.
- Do not stop prescribed psychiatric drugs to try it.
- Antidepressant and stimulant interactions: untested.
Our verdict on PE 22-28
Interesting target but mouse-only data. Human dose, safety and benefit are unknown.
PE 22-28 FAQ
What does PE 22-28 do?
It blocks TREK-1 in cells. Mice showed antidepressant-like behavior.
Is PE 22-28 the same as spadin?
No. It is a shorter 7-amino-acid piece designed to last longer.
Has PE 22-28 been tested in people?
No. I found no registered trial.
Sources
- Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity. Front Pharmacol 2017, PMID 28955242
- ClinicalTrials.gov search by intervention name, run 5 Nov 2026: 0 results
- Community reports summarised from public peptide-community notes (peptideprotocols.app page); user reports, not research