PE-22-28 Peptide: What It Is, What the Mouse Studies Found and the Dosage Maths

PE-22-28 is a 7 amino acid peptide cut down from spadin, a fragment of the sortilin protein that blocks a potassium channel in the brain called TREK-1. Researchers made it in 2017 as a faster, longer-acting antidepressant candidate, and in mice it worked after four days instead of the weeks antidepressants usually take. That is the whole evidence base: a handful of mouse and cell studies from one line of research. It has never been tested in people.

What PE-22-28 is

The story starts with TREK-1. Mice without the TREK-1 channel were resistant to depression "in five different models" and behaved like mice on fluoxetine (Heurteaux 2006, Nat Neurosci). Spadin, a 17 amino acid piece of the sortilin propeptide, turned out to block TREK-1 and act as an antidepressant in mice within four days (Mazella 2010, PLoS Biol). The 2017 paper shortened it: PE 22-28 is "a 7 amino-acid peptide" (Djillani 2017, Front Pharmacol), residues 22 to 28 of the propeptide, which on spadin's published sequence reads GVSWGLR (our reading of the two papers; the 2017 paper does not print it).

What the research shows

• Stronger on the channel. PE 22-28 blocked TREK-1 at an IC50 of 0.12 nM, against 40 to 60 nM for spadin, a few hundred times more potent in cells (Djillani 2017).
• Longer acting. In the forced swim test the effect of spadin "disappeared beyond 7 h"; the short analogs lasted "up to 23 h instead of 7 h".
• Antidepressant-like in mice. 30 minutes after one injection of 3 to 4 µg/kg, time spent immobile in the swim test fell from 161.7 seconds on saline to 91.8 seconds on PE 22-28. After 4 daily injections the effect held in a stress-hormone model of depression.
• New nerve cells. After 4 days, new cells in the hippocampus roughly doubled: 1,736 per hippocampus on PE 22-28 against 899 on saline.
• Stroke, mice. A short spadin analog the authors call mini-spadin protected mice after a stroke and prevented post-stroke depression (Pietri 2019). Whether mini-spadin is the same peptide as PE 22-28, the abstract does not say.

Spadin itself showed no anti-anxiety effect in the 2010 tests, and no study we found tested PE-22-28 for anxiety, focus or memory in healthy animals, the uses it is sold for.

PE-22-28 dosage: the mouse doses and what they convert to

ClinicalTrials.gov lists no study of spadin or PE 22-28 (registry search, 8 November 2026), so there is no human dose. The mice got micrograms per kilogram, which is tiny. The table converts them with the FDA body-surface factor (divide by 12.3; FDA guidance) for a 70 kg adult; read the last column as arithmetic, not a dose.

Community numbers for PE-22-28 conflict with each other and none cites a source, so we do not repeat them. At microgram amounts, measuring is the hard part: a 10 mg vial in 2 mL holds 5 mg per mL, so 20 µg is 0.004 mL, less than half of one mark on a U-100 syringe. That is why a calculator, not a forum chart, should do the arithmetic.

Safety and sport

There is no human safety data at all, and no published study we found looked at its safety beyond the mouse behaviour tests. PE-22-28 is not named on the WADA 2026 list, but as a pre-clinical substance it falls under S0, non-approved substances, prohibited at all times (WADA).

Frequently asked questions

What is PE-22-28?

PE-22-28 is a 7 amino acid peptide made in 2017 by shortening spadin, a fragment of the sortilin propeptide. It blocks the TREK-1 potassium channel and acted as a fast antidepressant in mice.

What is the PE-22-28 dosage?

There is no human dose; no human study is registered. Mice got 3 to 4 micrograms per kg by injection. Converted by FDA's body-surface method for a 70 kg adult that is about 17 micrograms, which is arithmetic, not a dose.

Does PE-22-28 work for anxiety or focus?

No study we found tested it for anxiety, focus or memory in healthy animals. The evidence is antidepressant-like behaviour, new hippocampal cells and stroke recovery in mice; its parent peptide spadin showed no anti-anxiety effect.

How is PE-22-28 different from spadin?

It is the last 7 of spadin's 17 amino acids. In cells it blocked TREK-1 at 0.12 nM against 40 to 60 nM for spadin, and in mice its effect lasted up to 23 hours against 7 for spadin.

Is PE-22-28 banned by WADA?

It is not named on the 2026 list, but as a pre-clinical substance with no approval for human use it falls under S0, non-approved substances, prohibited at all times.

Sources (checked 8 November 2026)

1. Djillani A et al. Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity. Front Pharmacol 2017;8:643. Checked 8 November 2026.
2. Mazella J 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. Checked 8 November 2026.
3. Heurteaux C et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat Neurosci 2006;9(9):1134-1141. Checked 8 November 2026.
4. Pietri M et al. First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. Neuropharmacology 2019;158:107715. Checked 8 November 2026.
5. ClinicalTrials.gov search for spadin or PE 22-28, 8 November 2026. Checked 8 November 2026.
6. FDA guidance: Estimating the maximum safe starting dose in initial clinical trials, 2005. Checked 8 November 2026.
7. WADA 2026 Prohibited List. Checked 8 November 2026.

PE-22-28 is an unapproved research compound; every figure is from the mouse and cell studies listed. Labels and trial records change; the leaflet in your box and your prescriber come first. Educational content, not medical advice.