PE-22-28, also called mini-spadin, is a synthetic 7-amino-acid peptide. It is a shortened version of spadin, a peptide that French researchers at the CNRS Institute of Molecular and Cellular Pharmacology described in 2010 as an experimental antidepressant. Both peptides block TREK-1, a potassium channel in nerve cells that has been studied as a target for depression.

The single most important fact: PE-22-28 has never been tested in humans. Every result published so far comes from mice or from cells grown in the lab, almost all of it from the single research group that created it. It is not an approved drug in any country, and no clinical trial is registered. It is often grouped with “nootropics” (supposed cognitive enhancers), but none of the published studies tested memory or learning in healthy animals or people.

This page summarizes what the laboratory and animal studies report. It is for education only and is not medical advice.

Property	Detail
Class	Synthetic peptide, 7 amino acids; experimental research compound
Other names	Mini-spadin; PE 22-28
Origin	Residues 22–28 of the 44-amino-acid propeptide released from the protein sortilin
Target	Blocks the TREK-1 potassium channel (cell studies)
Potency in cells	IC50 ≈0.1 nM, vs 40–60 nM for spadin (half-maximal blocking concentration)
Doses studied	Mice only: 3.0–4.0 μg/kg by injection into the abdomen (intraperitoneal) in most tests; 0.03 μg/kg in a stroke model; 1 mg/kg by mouth (gavage)
Half-life	No pharmacokinetic study published; antidepressant-like effects of two modified versions lasted about 14–23 h in mice
Human data	None; no trials registered on ClinicalTrials.gov
Approval	Not approved as a drug in any country
WADA	Not named, but falls under S0 (non-approved substances), prohibited at all times

What it is

The protein sortilin (also called neurotensin receptor 3) is made as a longer precursor. When it matures, a 44-amino-acid fragment called the propeptide, or “PE,” is cut off and released into the blood. In 2010 the Valbonne group showed that a 17-amino-acid piece of it, residues 12–28, blocked TREK-1 and had antidepressant-like effects in mice. They named it spadin (Mazella et al., PLoS Biol 2010).

Spadin had a practical problem: its effect in mice was gone within about 7 hours. To find a more stable version, the researchers incubated spadin in mouse serum, identified the fragments it broke down into, and tested shorter pieces on human TREK-1 channels expressed in cultured cells. The shortest piece that still blocked the channel was residues 22–28, which they named PE 22-28 (Djillani et al., Front Pharmacol 2017). A later review by the same group refers to it as mini-spadin (Mazella et al., Front Pharmacol 2018).

The 2017 paper also made 16 modified versions of PE 22-28, by adding chemical groups to either end or by swapping the first amino acid (glycine) for alanine. Three peptides were carried forward:

Peptide	Change from PE 22-28	IC50 for TREK-1 in cells
Spadin (PE 12-28)	Longer parent peptide, 17 amino acids	40 nM
PE 22-28	None	≈0.1 nM
G/A-PE 22-28	First glycine replaced by alanine	≈0.1 nM
Biotinylated G/A-PE 22-28	Alanine swap plus a biotin tag on the front end	1.2 nM

The paper gives the IC50 for PE 22-28 and G/A-PE 22-28 as 0.10 or 0.12 nM in different places, so they are shown here as ≈0.1 nM. Several other modifications, including fatty-acid and acetyl groups, weakened or abolished the blocking effect.

Why TREK-1

TREK-1 is a “background” potassium channel. When it is open, it makes neurons less excitable. In 2006 the same institute reported that mice lacking the TREK-1 gene behaved like mice treated with antidepressants: they resisted depression-like behavior in five different tests, showed stronger serotonin signaling and had a smaller corticosterone (stress hormone) rise under stress (Heurteaux et al., Nat Neurosci 2006). That finding is the rationale for TREK-1 blockers such as spadin and PE 22-28.

How it works in the body

There is no published pharmacokinetic study of PE 22-28 in any species. No absorption, peak level, half-life or route of elimination has been reported.

What is available are indirect measures from mice (Djillani et al., Front Pharmacol 2017):

Serum stability. The authors describe a “relatively short” serum half-life in the test tube, without giving a number.
Duration of effect. After a single injection, the antidepressant-like effect of two modified versions faded by half after about 14–17 h at 3.2–4.0 μg/kg and about 21–23 h at 32–40 μg/kg. This was not measured for unmodified PE 22-28, and spadin’s matching value was about 6 h.
Oral activity. Given by mouth (gavage) at 1 mg/kg for 4 days, the analogs still reduced immobility in the forced swim test. Whether the intact peptide reaches the blood or brain after oral dosing was not measured.

These are “half-effect times” from behavioral tests, not blood half-lives, and they come from modified analogs. They should not be read as the half-life of PE 22-28 in people.

Regulatory status

PE-22-28 has not been approved as a medicine anywhere. A search of ClinicalTrials.gov for “PE-22-28,” “mini-spadin” and “spadin” returned no registered studies (ClinicalTrials.gov).

In sport, the WADA 2026 Prohibited List prohibits at all times, in section S0, any pharmacological substance that has no current approval by a government health authority for human therapeutic use and is not covered elsewhere on the list. PE-22-28 is not named, but as an unapproved experimental drug it fits that definition.

What the research shows

All of the studies below were done in mice or in cell culture. None tested PE-22-28 in humans, and none studied muscle, growth hormone, body composition or physical recovery.

Depression-like behavior in mice

The main study is the 2017 paper that created the peptide (Djillani et al., Front Pharmacol 2017). It used male C57Bl/6J mice, with 10 mice per group in the behavioral tests. In the forced swim test, a standard screen for antidepressant drugs, less time spent floating motionless is read as an antidepressant-like effect.

Test (mice)	Treatment	Result vs saline
Forced swim, single dose, healthy mice	PE 22-28, 3.0–4.0 μg/kg, injection	Immobility 92 s vs 162 s (p under 0.0001)
Forced swim, single dose, corticosterone model	PE 22-28 3.0 μg/kg vs spadin 100 μg/kg	98 s (PE 22-28) and 117 s (spadin) vs 165 s
Forced swim, 4 days, corticosterone model	PE 22-28 vs spadin	90 s (PE 22-28) and 108 s (spadin) vs 158 s
Novelty-suppressed feeding, 4 days, corticosterone model	PE 22-28 3 μg/kg vs spadin 100 μg/kg	Latency to eat 153 s (PE 22-28) and 129 s (spadin) vs 226 s (p under 0.05)

The corticosterone model gives mice stress-hormone treatment for 7 weeks to produce depression-like behavior. A 4-day course of the analogs also shortened escape times in the learned helplessness test, another rodent depression model.

Brain cell growth

After 4 days of injections in mice, PE 22-28 roughly doubled the number of newly dividing cells in the hippocampus, a brain region involved in mood and memory (1,736 vs 899 labeled cells per hippocampus, n = 5 per group). In cultured mouse cortical neurons, 0.1 μM of the peptide raised levels of PSD-95, a protein marker of new synapses, over 36 hours (Djillani et al., Front Pharmacol 2017). Classical antidepressants usually need weeks of treatment to produce similar changes in rodents, which is why the group describes spadin-type peptides as potentially fast-acting.

Stroke in mice

In a mouse model of stroke, mini-spadin was injected at a low dose (0.03 μg/kg) once daily for 7 days after the stroke, then at a higher dose (3 μg/kg) 4 days a week (Pietri et al., Neuropharmacology 2019). The authors report that it:

prevented body-weight loss and the delayed loss of dopamine neurons in the substantia nigra;
improved stroke-related motor and cognitive deficits;
prevented depression-like behavior after the stroke in the forced swim and novelty-suppressed feeding tests.

In electrical recordings, the peptide activated TREK-1 at low doses and blocked it at higher doses. This two-way action means “TREK-1 blocker” is an incomplete description, and that effects may depend strongly on dose. The cognitive improvement here was recovery from stroke damage in mice, not enhancement in healthy animals.

Pancreatic beta cells

In cell-culture experiments, the natural propeptide, spadin and mini-spadin protected insulin-producing beta cells from death caused by the inflammatory signal interleukin-1β. Mini-spadin also increased beta-cell proliferation (Daziano et al., Pharmacol Res 2021). This has not been tested in animals with diabetes or in people.

Human data on the parent propeptide

No human has received PE 22-28 in a published study. The only human data concern the body’s own sortilin propeptide, measured in blood as a possible marker of depression, not as a treatment:

Serum propeptide levels were lower in patients with major depression than in healthy controls (p = 0.035), and returned toward normal with antidepressant drug treatment (Devader et al., J Affect Disord 2017).
In 45 patients with treatment-resistant depression, levels rose about a month after electroconvulsive therapy, but only in patients who responded (Roulot et al., Neuropsychiatr Dis Treat 2018).

These are small observational studies. They say nothing about whether taking a synthetic fragment would be safe or effective.

Side effects and risks

No human safety data

Because PE-22-28 has never been given to people in a published study, its side effects in humans are unknown. There is no information on safe doses, interactions with other drugs, effects in pregnancy, or long-term use.

What the animal and cell studies looked at

Other potassium channels. At 100 nM in cells, PE 22-28 did not affect four related channels (TREK-2, TRAAK, TRESK and TASK-1) (Djillani et al., Front Pharmacol 2017).
Heart rhythm channel. At 10 μM, the analogs did not change the current through hERG channels, the channel behind many drug-induced heart rhythm problems. This was a cell test only; no heart monitoring in living animals was reported for PE 22-28.
TREK-1-related risks. Mice lacking TREK-1 are more sensitive to pain, seizures and brain injury from loss of blood flow. In mice, the parent peptide spadin did not worsen pain, kainate-induced seizures, stroke size, blood pressure or heart function, and did not change blood glucose (Moha Ou Maati et al., Neuropharmacology 2012). These checks were done for spadin, not for PE 22-28 itself.

TREK-1 also works outside the brain; for example, it has been studied in heart rhythm disorders (Djillani et al., Front Pharmacol 2017). Whether long-term blocking of it in humans is safe has not been studied.

Product quality

Peptides sold online for “research use” are not made or checked under drug-manufacturing standards. We found no published study testing the identity, purity or sterility of commercial PE-22-28 products, so what a given vial contains is unknown.

Key takeaways

A shortened spadin fragment. PE-22-28 is a 7-amino-acid piece of a natural peptide cut from the protein sortilin, designed in 2017 as a more potent, longer-acting version of the experimental antidepressant spadin.
Potent in cells, tested only in mice. It blocked TREK-1 channels at about 0.1 nM in cell studies and reduced depression-like behavior in mice at microgram-per-kilogram doses.
No human studies. No trial has been published or registered, and there are no human pharmacokinetic, efficacy or safety data.
No measured half-life. The roughly 14–23 h figures describe how long behavioral effects of modified analogs lasted in mice, not the blood half-life of PE-22-28.
“Nootropic” claims are not supported. The cognitive findings come from recovery after stroke in mice; no study tested memory or learning in healthy animals or people.
Banned in sport. As an unapproved substance it falls under WADA’s S0 category, prohibited at all times.

Sources

Djillani A, Pietri M, Moreno S, et al. Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity. Front Pharmacol. 2017;8:643. PubMed; PMC.
Mazella J, Pétrault 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. PubMed.
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. 2018;9:1541. PubMed.
Heurteaux C, Lucas G, Guy N, et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat Neurosci. 2006;9(9):1134–1141. PubMed.
Pietri M, Djillani A, Mazella J, Borsotto M, Heurteaux C. First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. Neuropharmacology. 2019;158:107715. PubMed.
Daziano G, Blondeau N, Béraud-Dufour S, et al. Sortilin-derived peptides promote pancreatic beta-cell survival through CREB signaling pathway. Pharmacol Res. 2021;167:105539. PubMed.
Moha Ou Maati H, Veyssiere J, Labbal F, et al. Spadin as a new antidepressant: absence of TREK-1-related side effects. Neuropharmacology. 2012;62(1):278–288. PubMed.
Devader C, Roulot M, Moréno S, et al. Serum sortilin-derived propeptides concentrations are decreased in major depressive disorder patients. J Affect Disord. 2017;208:443–447. PubMed.
Roulot M, Minelli A, Bortolomasi M, et al. Increased serum levels of sortilin-derived propeptide after electroconvulsive therapy in treatment-resistant depressed patients. Neuropsychiatr Dis Treat. 2018;14:2307–2312. PubMed.
U.S. National Library of Medicine. ClinicalTrials.gov search for “spadin,” “mini-spadin” and “PE-22-28” (no registered studies; accessed October 2026). ClinicalTrials.gov.
World Anti-Doping Agency. The 2026 Prohibited List: International Standard. In effect January 1, 2026. WADA 2026 Prohibited List.

PE-22-28