Podcast episode 92 (in German)
PE-22-28 – the antidepressant that never reached a human
September 30, 2026
PE-22-28 is said to work against depression via a target that no approved antidepressant uses. The research behind it is serious and around 20 years old. To this day, there is not a single study in humans.
What it is about
It all begins in 2006 with mice lacking a particular potassium channel in the brain — TREK-1. In the usual tests, they behave as if they had been given an antidepressant. In 2010 a French group described spadin, a fragment produced by the body that blocks this channel; in 2017 PE-22-28 followed as a shortened, more potent and longer-acting version. The episode explains why a new target in depression really would be needed, and why the much-cited speed of onset comes from animal experiments. Because the decisive figure is a zero: no completed, no ongoing and no terminated study in humans. The substance is sold anyway.
Key points
- The idea goes back to an observation from 2006: mice lacking the potassium channel TREK-1 do better in the usual behavioral tests, without any medication at all.
- In 2010 a French group described spadin in PLoS Biology, a fragment that is left over when the receptor sortilin is trimmed and that blocks exactly this channel.
- The shortened version of 7 amino acids presented in 2017 blocks the channel considerably more potently, at 0.12 nanomolar, than spadin at 40 to 60, and lasts 23 instead of 7 hours in the body.
- In animal experiments the effect appeared after 4 days, whereas standard antidepressants take 3 to 4 weeks in humans — two measures that are not comparable.
- Around a third of patients do not respond well to the existing antidepressants; that is why a genuinely new target would be a gain here and not a warning sign.
- In the scientific literature and trial registries there is not a single study in humans on PE-22-28; a future entry would get a 0 on the evidence axis, not a 1.
- The missing step would be a comparatively small phase 1 study with 20 to 30 healthy volunteers on tolerability and blood levels.
Where the data stop
Everything known about PE-22-28 comes from cell and animal experiments. There is no safety profile in humans, no known interactions and no tested use. That blocking this channel looked unremarkable in mice is no statement about safety in a human. The much-cited fast onset, too, is a finding from behavioral tests in animals: what is measured there is how long an animal keeps struggling in an unpleasant situation, not hopelessness, self-reproach or loss of joy. Such tests respond reliably to drugs that work in humans and are therefore a good filter — but poor proof.
On top of that there is a limit that appears in no list of side effects. Depression is very treatable, with psychotherapy, with medicines tested in humans, usually with both. Weeks or months with an untested peptide are weeks or months without the treatment that helps. If this topic affects you, the next step is an appointment.
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Published on September 30, 2026.
The topic in the database
- PE-22-28 is the shortened, considerably more potent version of the body’s own peptide spadin and blocks the potassium channel TREK-1 in the brain. As an antidepressant …PE-22-28
Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-09-19.