PE-22-28 Peptide: What It Is, Evidence and Status

What Is PE-22-28?

PE-22-28 is a synthetic peptide made of seven amino acids: glycine, valine, serine, tryptophan, glycine, leucine and arginine. The name is a set of coordinates. Sortilin, a receptor protein found throughout the brain, is built with a 44-amino-acid tail called a propeptide (PE) that gets snipped off as the receptor matures, and positions 22 through 28 of that tail are PE 22-28. Some vendors call it mini-spadin, because it is a shortened version of spadin, the longer natural fragment (positions 12 through 28) the same French laboratory identified first.

What the peptide does is block one potassium channel, TREK-1. The channel sits in neurons of the prefrontal cortex, hippocampus and amygdala and leaks potassium out of the cell, which holds the neuron at a quiet, negative resting voltage. Mice engineered without it behave, across a battery of stress tests, like mice on antidepressant drugs. A molecule that plugs the channel might do the same thing faster than a drug that works on serotonin reuptake. That hypothesis is the entire reason PE-22-28 exists.

It is not an approved drug anywhere. Online it is sold as a research chemical in vials and, by some sellers, as a nasal spray, with benefit lists that run from mood to memory to stroke recovery. PeRx prescribes it inside one blend with Pinealon Read nextPinealon Peptide: What It Is, Evidence and DosingPinealon is three amino acids long, comes from one research institute in St. Petersburg, and is sold with a confidence its evidence does not support. Here is what the peptide actually is, why its name points at the wrong gland, what about twenty published studies do and do not show, why the dosing charts online disagree, and why we only prescribe it as one part of a three-peptide blend.Read article and Selank Read nextSelank Peptide: What It Is, What It Does & BenefitsYour immune system already makes a molecule that calms anxiety. Soviet scientists found it in the 1970s, reverse-engineered it, and created two peptides: one that quiets anxiety without sedation, and another that sharpens cognition through BDNF. Both have been prescription medications in Russia since 2009. Combined in a single injectable blend, Selank and Semax cover both sides of the equation: calm and sharp at the same time.Read article , and we would rather you see the size of the evidence file first. It is small.

From Sortilin to Spadin to PE-22-28

The story runs through one building: the Institut de Pharmacologie Moleculaire et Cellulaire in Valbonne, near Nice, a CNRS laboratory with decades of potassium channel work. The same names, Heurteaux, Mazella, Borsotto and later Djillani, appear on nearly every paper, which matters for how much weight the results can carry. Here is the sequence.

Heurteaux C, Guy N, Laigle C, et al. "TREK-1, a K+ channel involved in neuroprotection and general anesthesia." The EMBO Journal. 2004;23(13):2684-2695. View study

Heurteaux C, Lucas G, Guy N, et al. "Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype." Nature Neuroscience. 2006;9(9):1134-1141. View study

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 Biology. 2010;8(4):e1000355. View study

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. View study

Devader C, Khayachi A, Veyssiere J, et al. "In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin." British Journal of Pharmacology. 2015;172(10):2604-2617. View study

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." Frontiers in Pharmacology. 2017;8:643. View study

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. View study

How PE-22-28 Is Thought to Work

Most antidepressant drugs change how much serotonin or norepinephrine sits between neurons. PE-22-28 works one step earlier, on the electrical state of the neuron itself. The chain of reasoning from the papers above has four links.

The link vendors lean on hardest is the fourth one, the four-day neurogenesis figure, usually rendered as "grows new brain cells." In context it means a marker of cell division in the mouse hippocampus rose after four daily injections, an effect established antidepressants also produce, more slowly. Whether that has anything to do with how a person feels is a twenty-year argument in the field, and PE-22-28 has not been part of it, because it has not been given to people.

One wrinkle deserves its own sentence. In the 2019 stroke paper the lab reported that mini-spadin is biphasic: at a very low dose it increased TREK-1 activity, and only at a higher dose did it block the channel. The direction of the effect may therefore depend on how much you take, and no study has mapped where that line sits in a human being.

Djillani A, Mazella J, Heurteaux C, Borsotto M. "Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin." Pharmacology and Therapeutics. 2019;194:185-198. View study

What the Mouse Studies Measured

A PubMed search in September 2026 returns 41 records mentioning spadin and three naming PE 22-28 or mini-spadin. The table sorts the claims you will see on sales pages by the strongest evidence that actually exists for each.

The forced swim test, explained

The forced swim test does most of the work on the sales pages, so it is worth understanding. A mouse is placed in a cylinder of water it cannot escape, and researchers time how long it floats instead of swimming. Antidepressants shorten the floating, and so did PE-22-28. Many researchers now read the test as a measure of coping strategy under acute stress rather than of anything resembling depression, and it has flattered dozens of candidate antidepressants that later did nothing in people. Floating less in a beaker is not a mood.

Why single-lab evidence gets a discount

Every primary paper on spadin and PE-22-28 that we could find carries an author from the Valbonne institute, and we found no independent laboratory that has tried to reproduce the effects of the seven-amino-acid fragment. That is not an accusation. Unreplicated findings simply carry less weight: the people who design a molecule tend to run the experiments most likely to flatter it, and null results are published less often than positive ones.

The Stroke Experiments

Several vendor pages list stroke recovery as a benefit. The source is one 2019 mouse study. Mice had a stroke induced by blocking an artery. Thirty minutes later they received 0.03 micrograms per kilogram of mini-spadin into the abdomen, daily for a week, a tiny dose that activated TREK-1, the direction associated with brain protection. Then the dose rose a hundred-fold, to 3 micrograms per kilogram four days a week, to block the channel and act on mood. Treated mice lost less weight, kept more dopamine neurons, moved and learned better, and did not develop the depression-like behavior untreated stroke mice showed.

It is a clever design and a mouse study from the inventing lab, with a two-phase dosing scheme keyed to the hour of an induced stroke. Nothing in it says what a fixed daily dose does in a person who has not had a stroke, and it is no reason to use a compounded peptide after a stroke instead of emergency care.

What Nobody Has Measured

There is no published study of PE-22-28 in humans, by any route, at any dose. There is no human pharmacokinetic study, so nobody knows its half-life in a person, how much of a subcutaneous dose reaches the blood, or how much of that crosses into the brain. The 23-hour figure is from mice, which clear peptides differently. ClinicalTrials.gov lists no study of spadin or mini-spadin, and no toxicology has been published for the seven-amino-acid fragment.

Route is a second gap. The mouse experiments injected the peptide into a vein or the abdominal cavity, routes nobody uses at home. Neither the nasal sprays some sellers offer nor the subcutaneous injection US clinics use, PeRx included, has been studied. Long-term effects are unknown by every route, a gap our long-term safety guide Read nextAre Peptides Safe Long-Term? What the Data SaysMost safety questions about peptides assume the timeframe is one or two cycles. The harder question is what happens after a year, three years, or a decade. The honest answer is that peptides fall into three buckets: ones with multi-decade clinical data, ones with several years of safety record but limited long-term studies, and ones where the long-term picture is genuinely incomplete. Here is the bucket each peptide is in and what monitoring matters.Read article covers in general terms.

A third gap is metabolic, and it is the one finding from the lab that rarely reaches a sales page. TREK-1 channels also sit in the insulin-producing beta cells of the pancreas. In 2016 the group showed that blocking them with spadin depolarized those cells, potentiated insulin release in cell culture and isolated mouse islets, and raised glucose-stimulated insulin in living mice. The authors framed it as a possible diabetes therapy. For anyone on glucose-lowering medication or prone to low blood sugar, it is a reason for caution, and it is on our intake questionnaire for that reason.

Hivelin C, Beraud-Dufour S, Devader C, et al. "Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin." Journal of Diabetes Research. 2016;2016:3142175. View study

Finally, no study has tested PE-22-28 together with Pinealon and Selank Explore PeRxSemax/SelankCognitive Clarity & Calm FocusView peptide , the two peptides it shares a vial with at PeRx. The combination is a formulation decision built on non-overlapping mechanisms, not a tested protocol, and the blend guide Read nextPinealon, PE-22-28 & Selank Guide (2026)Three peptides, three layers of brain support. Pinealon restores sleep architecture through pineal gland regulation. PE-22-28 drives neurogenesis by blocking the TREK-1 potassium channel. Selank calms anxiety through GABA modulation without sedation or dependence. Together they rebuild, grow, and protect neural tissue from three independent angles.Read article says so.

PE-22-28 Dosing: Why There Is No Chart

Search for a PE-22-28 dosage and you will find confident microgram figures, nasal spray schedules and cycle lengths laid out in tables. None traces back to a dose-finding study, because none exists. The only tested doses are mouse doses: 3 micrograms per kilogram to block the channel, and a hundred times less to activate it. Scaling either to a person is guesswork, and the biphasic result means that getting the number wrong could, in principle, reverse the effect rather than weaken it.

PeRx does not prescribe PE-22-28 by itself, so there is no PeRx PE-22-28 dose to chart. What we can give you is the arithmetic of the blend it comes in.

Because all three peptides share one vial at one concentration, the PE-22-28 dose cannot rise without the other two rising with it. That suits people who want the combination and not anyone chasing a PE-22-28 number from a forum. Timing and cycle length are covered in the blend guide Read nextPinealon, PE-22-28 & Selank Guide (2026)Three peptides, three layers of brain support. Pinealon restores sleep architecture through pineal gland regulation. PE-22-28 drives neurogenesis by blocking the TREK-1 potassium channel. Selank calms anxiety through GABA modulation without sedation or dependence. Together they rebuild, grow, and protect neural tissue from three independent angles.Read article , and technique in how to inject peptides Read nextHow to Inject Peptides: Subcutaneous GuideA clear, practical walkthrough of subcutaneous peptide injections, from supply setup to sharps disposal. Written for patients new to self-injection with ready-to-use PeRx vials.Read article .

Why We Only Prescribe It Inside a Blend

A standalone PE-22-28 vial would ask you to pay for, and inject, a molecule whose entire record is mouse work from one laboratory. We were not comfortable building a product on that. Inside the blend, PE-22-28 is one of two speculative thirds, alongside Pinealon Read nextPinealon Peptide: What It Is, Evidence and DosingPinealon is three amino acids long, comes from one research institute in St. Petersburg, and is sold with a confidence its evidence does not support. Here is what the peptide actually is, why its name points at the wrong gland, what about twenty published studies do and do not show, why the dosing charts online disagree, and why we only prescribe it as one part of a three-peptide blend.Read article , next to Selank, which has a 62-patient clinical trial and a Russian prescription registration behind it. Read plainly, the case for the blend rests mostly on Selank for how you feel in the first weeks, with PE-22-28 as a mechanistically interesting addition nobody has tested in people.

If you want the combination, understanding that two of its three parts are early-stage, it is available after a provider reviews your intake. If what you want is calm focus with the best-supported peptide in the vial, Selank Read nextSelank Peptide: What It Is, What It Does & BenefitsYour immune system already makes a molecule that calms anxiety. Soviet scientists found it in the 1970s, reverse-engineered it, and created two peptides: one that quiets anxiety without sedation, and another that sharpens cognition through BDNF. Both have been prescription medications in Russia since 2009. Combined in a single injectable blend, Selank and Semax cover both sides of the equation: calm and sharp at the same time.Read article on its own is the cleaner choice, Semax vs Selank Read nextSemax vs Selank: Which One Do You Actually Need?Every page ranking for this question tells you to pick one: Semax for focus, Selank for calm. The split is useful and softer than the marketing admits. Here is what the single human head-to-head found, where the two run on the same machinery, where the FDA record splits them, and why a prescribing clinic puts both in one vial instead of making you choose.Read article sorts out which of the two fits, and our nootropic peptides overview Read nextNootropic Peptides for Brain Health (2026)Nootropic is a broad word that covers everything from a cup of coffee to a prescription molecule. This guide narrows it to the peptides people actually ask about for cognition, calm, and sleep. What the research supports, what it does not yet support, and how Semax, Selank, Pinealon, and DSIP differ from one another.Read article puts all of them side by side.

Pinealon/PE-22-28/Selank

PE-22-28 arrives as one ingredient of a single 5 mL vial, 2 mg/mL of each of the three peptides, made by a US 503A pharmacy and shipped cold with syringes and swabs in the box. The vial is ready to use with no reconstitution needed, so the dose you draw is the dose the prescription describes.

$299 for a one-month supply. You complete an online intake, a licensed provider reviews it, and checkout holds your card without charging it until a prescription is approved.

The only form in which PeRx prescribes PE-22-28.

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Side Effects and Who Gets Screened Out

With no human study, any side-effect list for PE-22-28 is theoretical, which is different from reassuring. What can be said comes from three places: the biology of the channel it blocks, the 2012 mouse screen of its parent compound, and what people on the blend report to us.

The channel biology raises three flags. TREK-1 knockout mice are more prone to seizures, so a blocker could in principle lower the seizure threshold; spadin did not in mice, but PE-22-28 itself was never put through that screen. Second, the insulin effect described above. Third, the peptide acts on serotonin circuits, so its interaction with SSRIs, SNRIs and MAO inhibitors is unknown, and in a vial that also contains Selank, psychiatric medication is the first thing our intake asks about.

What people on the blend report is modest: redness or a small bump at the injection site, vivid dreams in the first week or two, and an occasional mild headache. In a three-peptide vial none of that can be pinned on PE-22-28. We have no reports of seizures or low blood sugar, and we screen for both histories before a prescription is considered.

FDA and Anti-Doping Status

Put plainly, the FDA has never evaluated PE-22-28 for compounding, favorably or unfavorably. That leaves it in a regulatory gray zone with its status unsettled. The nearest reviewed comparison is Semax Read nextSemax Peptide: What It Is, Uses, and the EvidenceSemax is a seven-amino-acid peptide designed in Moscow, registered in Russia as nasal drops, and sold in the United States mostly by chemical suppliers. This guide covers what it is, what the studies in rats and in people actually show, what FDA reviewers concluded in 2026, who gets screened out, and why PeRx prescribes it only inside an injected blend with Selank.Read article : in May 2026 FDA staff set aside foreign-language papers without verified translations, noted the absence of human pharmacokinetic and animal toxicology data, and found insufficient evidence for the uses proposed. PE-22-28 has no human papers in any language, so the same review would have less to work with. We will update this section if that changes; our FDA panel write-up Read nextFDA Panel Backs 6 of 7 Peptides, Rejects DSIPThe FDA's Pharmacy Compounding Advisory Committee finished its two-day meeting on July 24, 2026. By the end, it had voted to recommend six of the seven peptides on the agenda for the 503A compounding list, including BPC-157, TB-500, MOTS-C, Semax, and Epitalon, and against just one, Emideltide (DSIP). Every vote went against the FDA's own scientists. Here is the full tally, what it changes, and what it does not.Read article covers the peptides that were voted on.

Anti-doping is a separate question. PE-22-28 is not named on the 2026 World Anti-Doping Agency Prohibited List, but the S0 catch-all class prohibits at all times any substance with no current approval by a governmental health authority for human therapeutic use, and PE-22-28 fits that description exactly. Tested athletes should treat it as prohibited; anti-doping laboratories can test for peptides whether or not they are named. Peptide therapy for athletes Read nextPeptide Therapy for Athletes: WADA Rules & UseAthletes were among the earliest adopters of peptide therapy, and for good reason. Faster recovery between training sessions, accelerated injury repair, and improved body composition are directly relevant to athletic performance. But there are rules, and understanding the competitive landscape matters as much as the pharmacology.Read article goes through the wider picture, and do peptides show up on a drug test Read nextDo Peptides Show Up on a Drug Test?The short answer for most people is no. Standard employment and DOT drug screens do not test for therapeutic peptides. Anti-doping testing in competitive sport is a separate system with dedicated peptide detection, and that is where the answer changes. Here is the honest, clinic-side breakdown of who is tested, for what, and what it means if you are prescribed peptides.Read article covers which tests look for what.

PE-22-28: Common Questions