PE-22-28: what it is and what the evidence says
A seven-amino-acid peptide derived from spadin that inhibits the TREK-1 potassium channel and in doing so makes serotonin neurons easier to activate. In mice it is associated with antidepressant-like behavior, neurogenesis, and synapse formation in the hippocampus.
Last reviewed: August 16, 2026 · How we verify this
The ground it plays on
The brain adapts by forming and strengthening connections. Neurotransmitters take part in that conversation, along with factors that help neurons survive and grow. Compounds in this group are studied for their relationship with focus, memory, mood or neuroprotection — and it is worth saying plainly that this is the area where claims are most exaggerated and where human evidence is thinnest.
What it is studied for
Mood, focus, neuroprotection.
There is a distinction that almost always gets lost. A compound being studied for something is not the same as achieving it. And even where it works in a dish or in a mouse, that says little about whether it works in a person or whether the benefit is worth the risk. The section below therefore carries more weight than everything above it.
What the human evidence says
There are still no trials in which it is given to people. In humans there are only observational studies of the natural propeptide it derives from: its blood levels are lower in people with major depression (Journal of Affective Disorders, 2017) and track with depression scores after a stroke (Journal of the Neurological Sciences, 2025).
The limitation that matters most
The efficacy evidence comes from mice and cell cultures, and most of it was generated with spadin; what is specific to PE-22-28 comes from one 2017 study. Pharmacokinetic, safety, and efficacy data in people are still missing, and the nasal route has not been characterized.
Regulatory status
Research compound, with no approval from the FDA, the EMA, or any other agency. It is not listed by name on the 2026 WADA Prohibited List; with no approval for human therapeutic use, it falls under category S0, prohibited at all times for athletes subject to anti-doping control.
Status can change and varies by country. Always verify the rules in force where you live before drawing conclusions.
Cautions and context
Watch for signs of excess serotonin (agitation, sweating, tremor) if it is combined with antidepressants, and for any euphoria or marked insomnia. Because TREK-1 is also present in the heart and pancreas, blood pressure, pulse, and glucose are tracked; there are no studies in people yet.
With antidepressant treatment, bipolar disorder, diabetes, epilepsy, arrhythmias, or an emotional crisis, have a professional assess it before you start and while you are on it.
What this page cannot give you
A reference page can take you this far. You know what PE-22-28 is and where its research stands, which already puts you ahead of most readers. Four questions remain that no encyclopedia can answer for you, because the answers depend on your own situation:
- What would you measure beforehand, so that later you could tell whether anything actually changed?
- What would you watch along the way, and how consistently?
- What would you ask a professional, and in how much detail, so you do not walk out with a textbook answer?
- What would make you stop?
That is what the course is for
PeptiXtreme is ${CIF.LECCIONES} lessons that hand out no numbers. Each one ends with your starting point, what to watch along the way, the specific questions you take to a professional and the signals that mean stop. It includes per-module exams, a Certificate of Completion with a verifiable certificate ID, a Progress Tracker to follow how you are doing, and a human advisor you can actually write to.
See the course → Or measure your judgment, freeReferences
Every entry links to its record on PubMed, the US National Library of Medicine database. Open them and check. We would rather have a reader who verifies than one who takes our word for it.
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activitypreclinical Front Pharmacol · 2017 · PMID 28955242 →
- Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug designpreclinical PLoS Biol · 2010 · PMID 20405001 →
- First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptidespreclinical Neuropharmacology · 2019 · PMID 31325429 →
- Sortilin-derived peptides promote pancreatic beta-cell survival through CREB signaling pathwaypreclinical Pharmacol Res · 2021 · PMID 33737242 →
- In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadinpreclinical Br J Pharmacol · 2015 · PMID 25598009 →
- Fighting against depression with TREK-1 blockers: Past and future. A focus on spadinreview Pharmacol Ther · 2019 · PMID 30291907 →
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Frequently asked questions
What is PE-22-28?
A seven-amino-acid peptide derived from spadin that inhibits the TREK-1 potassium channel and in doing so makes serotonin neurons easier to activate. In mice it is associated with antidepressant-like behavior, neurogenesis, and synapse formation in the hippocampus. It is studied within the area of cognitive.
Is there human evidence for PE-22-28?
There are still no trials in which it is given to people. In humans there are only observational studies of the natural propeptide it derives from: its blood levels are lower in people with major depression (Journal of Affective Disorders, 2017) and track with depression scores after a stroke (Journal of the Neurological Sciences, 2025).
Is it approved by any health agency?
Research compound, with no approval from the FDA, the EMA, or any other agency. It is not listed by name on the 2026 WADA Prohibited List; with no approval for human therapeutic use, it falls under category S0, prohibited at all times for athletes subject to anti-doping control.
What is the dose of PE-22-28?
We do not publish dosages. This is not an oversight. No single figure works for everyone: the regimen depends on a person's medical history, on whatever medication they already take, and on the goal they are chasing, which is something a professional weighs with the case in front of them. What you can build is the ability to walk into that appointment knowing what to ask.
Where can I learn to evaluate this properly?
This page tells you what PE-22-28 is and what the evidence says. The PeptiXtreme course teaches the other half: what you would measure before considering anything, what you would watch, the specific questions you would take to a professional and when you would stop.