PE 22-28
An experimental peptide derived from spadin, studied in animals as a potential fast-acting antidepressant via the TREK-1 channel. It is at an early research stage with no human trials and no approved use.
Quick take
- What it is: a short experimental peptide derived from spadin, studied as a potential antidepressant.
- What people use it for: there is no established human use; interest is in depression and mood based on animal work.
- What we actually know: effects are described in animal (mostly rodent) studies via the TREK-1 potassium channel; there are no human trials.
- Status: an early-stage research compound; not approved by the FDA or other regulators for any use.
What it is
PE 22-28 is a short experimental peptide derived from spadin, a naturally derived peptide that has been studied as a potential fast-acting antidepressant. PE 22-28 is an analogue designed to retain that activity, and interest in it comes almost entirely from animal research.1
It is at an early research stage, with no established human use and no approved medical formulation.
How it works
PE 22-28 is thought to act by blocking the TREK-1 potassium channel, a target implicated in mood regulation. Inhibiting TREK-1 has been associated in animal models with antidepressant-like effects and with changes in neuronal signalling and plasticity.1,2 Whether this translates to humans is entirely unknown, as it has not been tested in people.
What the evidence shows
Animal studies
In rodent models, spadin-derived peptides including PE 22-28 have shown antidepressant-like effects with a reportedly rapid onset, along with signals of neuroprotection and increased neuroplasticity.2 This animal work is the entire basis for current interest in the peptide.
Human studies
There are essentially no published human clinical trials of PE 22-28. Its effects, optimal dosing and safety in people are unknown, and the animal results should not be assumed to translate.3 This is the single most important point: it is a preclinical compound.
Dosages reported in the literature
Informational only. The figures below reflect that no human dosing exists. This section is not a recommendation or a prescription, and any use should be discussed with a qualified healthcare professional.
| Setting | Route | Reported range |
|---|---|---|
| Animal studies | Injection | Used in rodent-scaled doses; not applicable to humans |
| Human use | — | None — no human trials or approved dosing |
Because there are no human dose-finding studies, no range here should be read as established as safe or effective in people.
Safety & side effects
The human safety profile of PE 22-28 is unknown because it has not been studied in people. Animal data cannot be assumed to predict human safety, and there are no long-term controlled safety studies of any kind.3
As with any peptide sold outside a regulated supply chain, product purity and dose accuracy vary between sources, which is an added concern for what is otherwise a research-only compound.
Legal & regulatory status
PE 22-28 is not approved by the FDA or other regulators for any use. It is an early-stage research compound, and its legal status for sale and use varies by country and changes over time.1
References
- Mazella J, Borsotto M, Heurteaux C. The Involvement of Sortilin/NTSR3 in Depression as the Progenitor of Spadin and Its Role in the Membrane Expression of TREK-1. Front Pharmacol. 2019;9:1541. [PMID 30670975, doi:10.3389/fphar.2018.01541]
- Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017;8:643. [PMID 28955242, doi:10.3389/fphar.2017.00643]
- Mazella J, Petrault O, Lucas G, et al. Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design. PLoS Biol. 2010;8(4):e1000355. [PMID 20405001, doi:10.1371/journal.pbio.1000355]