PE-22-28 is a shortened analogue of spadin, a peptide fragment released when a neurotensin receptor precursor is processed. It blocks TREK-1 — a potassium channel — and that is what makes it interesting: TREK-1 blockade is a genuinely different antidepressant mechanism from anything in clinical use.
The appeal in the animal work is speed. Conventional antidepressants take weeks to act, and the delay is the single worst feature of treating depression pharmacologically. TREK-1 blockade produced antidepressant-like effects in mice within days, alongside increased neurogenesis.
That is where it stops. There is no human trial of PE-22-28, and the history of antidepressant mechanisms that worked in mice and failed in people is long enough to be its own field. Anyone considering this for depression should weigh that against a fast-acting animal result.
How it works
PE-22-28 blocks TREK-1, a two-pore potassium channel expressed in brain regions involved in mood regulation. Mice lacking TREK-1 show a depression-resistant phenotype, which is what made the channel a target.
Blocking it increases neuronal excitability in those regions and, in animal work, raises hippocampal neurogenesis, the same downstream marker conventional antidepressants eventually produce, reached by a different route and faster.
It is a shortened form of spadin, engineered for better stability than the parent peptide. The parent itself was already a fragment, not a designed drug.
None of this is established in humans. TREK-1's role in human mood is inferred from animal genetics rather than demonstrated directly.
Regulatory status — United States
Not approved anywhere and never studied in a human trial. Developed in academic research; no clinical programme has reported. Sold only as a research chemical.
Last reviewed 18 Aug 2026. Regulatory positions in this category change frequently; we date this line so you can see how current it is.
What it is studied for
Each entry states the evidence behind it. We do not rank indications by effectiveness — for most compounds here, that would be a claim nobody can support.
Depression
Published reviewWhat the research targeted.
EvidenceAntidepressant-like effects within days in mouse models, with increased neurogenesis. No human trial exists.
Mood and wellbeing in healthy people
Community practiceWhy it is bought.
EvidenceNever studied. The animal work models depression. That is not the same as improving normal mood.
Identity and clearance
Molecule
- Class
- Spadin analogue, TREK-1 potassium channel blocker
- Length
- 7 amino acids
A shortened, stabilised version of spadin, itself a fragment of a neurotensin receptor precursor.
Dose protocols reported in sources
Displayed for reference only. Every row says where it came from, and a trial protocol and a community convention are not the same kind of information. None of this is fed into the calculator, and none of it is a recommendation.
| Goal | Dose | Frequency | Route | Units, 5 mg vial | Source | Start this protocol |
|---|---|---|---|---|---|---|
| Commonly described community protocol | 200 mcg – 800 mcg | Once daily, often in short courses | NasalNo human pharmacokinetic study exists. These figures are conventions rather than anything scaled from the animal work. | 12–48 u | Community practice | Start this |
Start this copies a row into a protocol of your own, which you can then edit. Where a source gave a dose range or an ambiguous frequency, those fields arrive empty — we will not pick a number on your behalf.
CheckRows marked community practice describe what people commonly do, drawn from public discussion. They are not derived from any trial and are not evidence that a dose is safe or effective.
Calculator
Work out what to draw
Pre-filled with a 10 mg vial as a worked example. These are not recommended values — change them to match the vial in front of you.
Draw to 10 units on a 1 mL U-100 syringe. That is 0.1 mL, containing 500 mcg of PE-22-28.
10 units sits exactly on a printed line.
Bioalmanac performs arithmetic on values you enter. It does not recommend doses, schedules or compounds, and nothing here is medical advice. Confirm every calculation against your vial and syringe before drawing, and speak with a licensed healthcare provider.
Open this calculation in the full calculator
Units, concentration, bacteriostatic water — the glossary defines the vocabulary, and a unit is not a fixed volume.
Safety
Reported effects
- EverythingCommunity practice
Unknown
No human study exists at any dose by any route.
- Headache and nasal irritationCommunity practice
Anecdotally reported
- Effects of blocking a potassium channel outside the brainPublished review
Unknown
TREK-1 is not confined to mood-regulating regions. It is expressed elsewhere — including in tissue where excitability matters a great deal — and nothing establishes what systemic blockade does.
When to stop
- Worsening mood, agitation, or any thought of harming yourself. Seek help immediately.
- Palpitations or an irregular heartbeat.
- Any new neurological symptom, including seizure activity.
- Any allergic response: rash, hives, facial swelling or difficulty breathing. Seek urgent care.
Interactions and situations that need care
- Depression, or any psychiatric conditionAvoid
This is the population the compound is bought for and the one where using it makes least sense. Depression is treatable with drugs that have decades of trial evidence, and substituting an unstudied peptide in a condition that can end in suicide is the highest-stakes version of this whole category's problem.
- Antidepressant or other psychiatric medicationAvoid
Adding an uncharacterised compound acting on neuronal excitability to an existing psychiatric regimen is an interaction nobody can predict, and stopping established treatment to try it is worse.
- Any cardiac arrhythmiaAvoid
Potassium channels govern cardiac repolarisation, and drugs that block them are a well-known cause of dangerous arrhythmias. Nothing establishes that this one spares the heart.
- Pregnancy and breastfeedingAvoid
No safety data of any kind, for a compound acting on neuronal excitability through a channel whose role in human development is unstudied.
What to expect
HonestlyThere is no human efficacy data for this compound, so there is no evidence-based timeline to give. Any site publishing a week-by-week schedule of expected effects has invented it.
- The mechanism is genuinely novel and the animal results are fast-acting. This is why it attracts attention.
- No human has ever been studied on it.
- Antidepressant mechanisms that work in mice and fail in people are close to a rule, not an exception.
- Potassium channel blockade is not confined to the brain, and the cardiac version of that effect is a known danger.
- If you are treating depression, the treatments with evidence behind them are the ones to start from.
Storage and handling
- Freeze-dried powder
- Refrigerated at 2–8 °C, protected from light.
- After mixing
- Refrigerated at 2–8 °C. Nasal solutions are handled more than injectables and are correspondingly easier to contaminate.
- Long-term, frozen
- Unopened powder is stable at −20 °C or colder.
Checking your vial
Research chemicals carry no manufacturing standard, so what the vial looks like is often the only quality signal available before you use it. More on assessing quality and COAs.
White cake, clear solution
Standard for a short peptide.
Collapsed cake or cloudy solution
Heat damage or degradation. Do not use it.
Questions
- What is TREK-1?
- A potassium channel in brain regions that regulate mood. Mice bred without it are resistant to depression-like behaviour. That is what made blocking it a target. It is a different mechanism from every antidepressant in clinical use.
- Why does the speed matter?
- Conventional antidepressants take weeks, and that delay is the worst feature of treating depression with drugs. In mice this acted within days. Whether that transfers to people is entirely unknown.
References
Spadin analogues and TREK-1 blockade as a rapid antidepressant mechanism
Neuropharmacology literature, 2015 · Animal studies
Mice
TREK-1 blockade produced antidepressant-like effects within days alongside increased hippocampal neurogenesis, faster than conventional antidepressants in the same models. No human studies have been conducted.
Commonly reported community protocols
Bioalmanac editorial summary of public community sources, 2026 · Not a study
Records dose and route patterns described in public discussion. Carries no evidential weight about safety or effect.
Related compounds
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A selective growth hormone secretagogue that prompts a short pulse of GH release. Widely used, and supported almost entirely by early pharmacology rather than outcome trials.
CJC-1295
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Tesamorelin
A GHRH analogue approved by the FDA for reducing excess visceral fat in HIV-associated lipodystrophy. The only compound in this category with completed phase 3 trials.
Next
What to do with PE-22-28
- Keep a record of itTurn a dose and a schedule into a protocol, then log what you actually take. PE-22-28 is filled in for you.
- See what it costsPer-milligram prices read from vendor sites and confirmed by a person, so vial sizes compare.
- Check a combinationWhat our profiles record about PE-22-28 alongside each other compound — including the pairs where nothing is recorded.
Keep this page honest
If something here is wrong, out of date, or missing a source, tell us and we will fix it and say that we did.
This page is educational. It describes what published research reports, not what you should do. Peptides discussed here are largely not approved for human use, and nothing on Bioalmanac is medical advice. No clinician reviews these pages.
Page last updated 18 Aug 2026