PE22-28
guinea pig
The Dose Guy’s verdictSep 1, 20261 source
PE22-28 is a single-paper compound. One study, mice and cells, 2017. The mechanism is interesting: it hits the TREK-1 potassium channel harder than its parent spadin, produces antidepressant-like behavior in mice within days, and triggers neurogenesis. But one unreplicated mouse paper is not evidence, it is a hypothesis with a DOI. Running it means generating the data yourself.
What it is
A seven-amino-acid peptide derived from spadin, itself a fragment of the sorting protein sortilin. Spadin blocks the TREK-1 potassium channel, and earlier research showed TREK-1 knockout mice display antidepressant-like behavior, which is the entire rationale. PE22-28 is a shorter, more potent version: its potency against TREK-1 is roughly 300 to 500 times greater than spadin’s in cell assays, and it lasts longer in vivo.
On the nootropic shelf PE22-28 sits as one of the more speculative entries. If the antidepressant-neurogenesis angle is what draws you, NSI-189 at least has human trial data behind it. PE22-28 has one paper from the originating lab and nothing else. No other group has published on it, and no human has taken it in a controlled setting.
What the research shows
One paper is the entire foundation. It is a good paper, but it is one paper.
Realistic protocols
I am not writing a dosing table from a single mouse paper. Forum lore runs PE22-28 at roughly 50 to 500 mcg subcutaneously or intranasally, but that range is guesswork with no human PK behind it. If you run it anyway: start at the low end, keep the cycle very short, and understand that you are generating the safety data, not following it.
Side effects
No human safety data exists. Not thin data, zero data:
