Potent TREK-1 blockade
PE-22-28 was designed to inhibit the two-pore potassium channel TREK-1, a target linked experimentally with mood pathways.
Explore the research →TREK-1 & MOOD-PATHWAY RESEARCH
PE-22-28
An early-stage brain research peptide attracting interest around mood, neurogenesis and cognitive health. Evidence is currently preclinical.
TREK-1 inhibitionMood-pathway researchNeurogenesis
A focused preclinical signal with no human treatment evidencePE-22-28 has a clear molecular target and encouraging mouse-model findings. No controlled human trial has established antidepressant benefit, pharmacokinetics, a dose or long-term safety.
FOLLOW THE FULL PICTUREFrom interest to evidence, quality and the numbers.
Why has PE-22-28 attracted research interest?
PE-22-28 attracts interest because it approaches mood through a different biological pathway from conventional serotonin-based antidepressants. Animal research linking that pathway with mood and new brain-cell growth has made it an intriguing early-stage compound in the cognition and mental-health space.
Antidepressant-like behaviour
Mouse behavioural tests produced the principal benefit signal associated with PE-22-28.
Explore the research →Neurogenesis signal
Short treatment was associated with markers of hippocampal neurogenesis in mice.
Explore the research →Longer experimental action
The shortened analogue was created to improve stability and activity compared with parent spadin.
Explore the research →THE SCIENCE BIT
A different route into mood-related biology.
PE-22-28 is a shortened spadin analogue studied for inhibition of TREK-1, a potassium channel involved in the electrical behaviour of cells. A channel is a pore, rather than a hormone receptor.
Mouse experiments report antidepressant-like behaviour and neurogenesis-related signals. Those findings make it a research lead; they do not establish an antidepressant treatment for people.
See the studies & trials →- TREK-1
- Potassium-channel target
- Electrical behaviour
- Channel activity influences cells
- Neurogenesis
- Experimental follow-up signal
How this connects to the research
A preclinical channel-based mechanism, without established human efficacy.
Read a primary source ↗FROM MOLECULE TO TISSUE
Where PE-22-28 connects with the body
These are the tissues and biological systems behind the interest in PE-22-28.
- Neuron membranes
- Potassium-channel activity.
- Hippocampal models
- Cell-generation research.
- Brain networks
- Preclinical mood studies.
The research behind the interest
Potent TREK-1 blockade
PE-22-28 was designed to inhibit the two-pore potassium channel TREK-1, a target linked experimentally with mood pathways.
The 2017 study reported an in-vitro IC50 of 0.12 nM and selectivity for TREK-1, but target potency does not predict a safe or effective human dose.
Strong mechanistic evidenceExplore the studies →Antidepressant-like behaviour
Mouse behavioural tests produced the principal benefit signal associated with PE-22-28.
Reduced immobility in forced-swim testing is an experimental screening outcome, not evidence that depression improves in people.
Animal evidence onlyExplore the studies →Neurogenesis signal
Short treatment was associated with markers of hippocampal neurogenesis in mice.
The finding supports biological follow-up, but cell-generation markers cannot establish improved mood, cognition or resilience in humans.
Preclinical evidenceExplore the studies →Longer experimental action
The shortened analogue was created to improve stability and activity compared with parent spadin.
Mouse data suggested activity lasting about 23 hours versus roughly seven hours for spadin; human exposure and half-life are unknown.
Comparative animal evidenceExplore the studies →Studies & trials
Studies & trials
Original publication · PubMed · trial registry where availableShortened spadin analogues: TREK-1 inhibition, stability and antidepressant activity ↗
Transfected cells, neuronal preparations and mouse behavioural models
PE-22-28 showed sub-nanomolar TREK-1 inhibition and selectivity in the experimental systems used.
The analogue produced antidepressant-like behavioural and neurogenesis signals in mice with longer reported action than spadin; no people were treated.
Spadin establishes the sortilin–TREK-1 research concept ↗
Cell systems, brain slices and mouse models
The parent peptide spadin bound to and inhibited TREK-1 and produced antidepressant-like effects in mice.
This study explains the design rationale for PE-22-28 but does not test PE-22-28 itself or establish a human treatment.
Human clinical-trial status ↗
No registered interventional human programme identified
The evidence base remains preclinical rather than a dose-finding or efficacy programme in people.
A registry search is useful for status, but absence of a record does not itself prove that no exposure has ever occurred.
Evidence snapshot
Evidence snapshot
Separate dimensions, not one overall score◎
Human evidenceEarly
1/5 evidence depth
No administered-human PE-22-28 study was identified.
✓
Clinical efficacyEarly
1/5 evidence depth
Antidepressant or cognitive efficacy has not been tested in a controlled human trial.
◇
Safety evidenceEarly
1/5 evidence depth
Human pharmacokinetics, psychiatric adverse effects, interactions and long-term safety are unknown.
⌁
Preclinical evidenceStrong
4/5 evidence depth
Direct cell and mouse work supports TREK-1 blockade, behavioural and neurogenesis hypotheses.
HOW TO READ THESE SCORESStrong preclinical evidence · early human evidence
These are editorial evidence-depth ratings on a 1–5 scale, not a statistical result or a single scientific formula. They summarise how much relevant evidence is present in each separate category and how mature that evidence is.
Human evidenceHow much direct research in people is available and how developed it is.
Clinical efficacyWhether human studies demonstrate meaningful outcomes for the claims being discussed.
Safety evidenceHow much human safety, tolerability and longer-term follow-up information is available.
Preclinical evidenceThe depth of laboratory and animal research supporting biological plausibility.
EVIDENCE LANDSCAPEPE-22-28Mechanism → measured response → clinical outcome
No administered-human trial identified
Direct TREK-1, behaviour and neurogenesis work
Human exposure, psychiatric outcomes and long-term safety
Keep route, study setting and outcome together
A measured biological response can be valuable evidence without establishing a self-administered protocol or a durable treatment benefit.
From promising signals to human evidencePreclinical research can reveal promising biological signals. Human studies show how far those signals have translated into real-world outcomes.
What people are exploring
COMMUNITY · USE CASES & EXPERIENCE
What people want to change with PE-22-28
PE-22-28 is discussed around mood, motivation, cognitive flexibility and rapid-onset effects. The strongest available paper supports TREK-1 biology in mice, while every practical human outcome remains anecdotal.
Explore the everyday goalsConceptual scientific illustration
THE PRACTICAL ATTRACTION
The goals behind the interest
What the desired change means in daily life, and what makes an experience useful to understand.
Mood, motivation and getting started
Interest focuses on low drive, emotional heaviness and difficulty initiating tasks. The TREK-1 research story attracts attention, but the treatment-benefit evidence is primarily preclinical.
- What makes a report informative
- Meaningful daily function and mood over time.
- What can muddy the picture
- Changes in depression-like animal behaviour cannot establish an antidepressant effect in people.
A rapid subjective shift
Some interest centres on whether a change might be felt quickly. An immediate sensation and a sustained improvement in wellbeing are different outcomes and should be described separately.
- What makes a report informative
- Whether a perceived change persists and improves functioning.
- What can muddy the picture
- Expectancy and normal mood variation can create strong short-term impressions.
Cognitive flexibility and clarity
People may connect mood research with clearer thinking or easier problem-solving. These broader cognitive hopes require their own evidence rather than being assumed from the channel mechanism.
- What makes a report informative
- Task performance alongside mood and alertness.
- What can muddy the picture
- Neuroplasticity language does not prove a measurable cognitive benefit.
PUT THE EXPERIENCE IN CONTEXT
How the goals compare with the research
Open an area to distinguish human findings from laboratory explanations.
Mood and motivation
People are drawn to a mechanism that differs from familiar monoamine-focused antidepressants.
Human findings & limits
No controlled human PE-22-28 mood study was identified.
Laboratory & animal context
Mouse screening tests showed antidepressant-like behaviour after PE-22-28.
What this means: A coherent animal signal, not evidence of an antidepressant effect in people.
Faster perceived onset
Short-latency reports are often linked to the rapid preclinical spadin story.
Human findings & limits
No human onset, exposure or dose-response study exists.
Laboratory & animal context
The parent and analogue programmes reported rapid behavioural signals in mice.
What this means: Timing from animal tests cannot validate a same-day human effect.
Neuroplasticity and clarity
Users extend the hippocampal neurogenesis result toward learning and flexible thinking.
Human findings & limits
No cognitive or neuroimaging endpoint has been tested in people.
Laboratory & animal context
Hippocampal neurogenesis markers increased after short treatment in mice.
What this means: An interesting biological signal whose practical cognitive meaning is unknown.
Simple intranasal cycles
Low-microgram nasal routines are repeated because they sound conservative and convenient.
Human findings & limits
No study validates nasal absorption, spray delivery, cycling or maintenance.
Laboratory & animal context
The main paper used experimental animal administration and cannot provide a retail nasal conversion.
What this means: A recognizable community pattern with no clinical calibration.
Research sources and further reading
Dose & duration
DOSE & DURATION
Research protocols · community patterns · calculator toolsSee the numbers in their proper context
See the amount, how often it was used and how long each study ran. Published human research and community descriptions each carry their own source label, so you can see where the numbers came from.
Source matters. The figures below show authorised, human-research or community-described protocols in their original context — not a personalised recommendation.
ONE ANECDOTAL COMMUNITY EXAMPLE
ANECDOTAL · UNVALIDATEDA cautious nasal example with no human calibration
This visual reflects a recurring community pattern. There is no human dose-finding study from which to derive a validated amount, route or schedule.
1Days 1–3
100 mcg · once dailyAnecdotal intranasal starting amount
2Days 4–7
100–200 mcg / dayOptional community-described step
3Weeks 2–4
Up to 300 mcg / dayUpper end of recurring descriptions
4After review
Stop or pauseNo validated cycle or break interval
What people commonly discuss100–300 mcg intranasally once daily for roughly four to eight weeks, sometimes followed by a two-to-four-week pause.
What remains unvalidatedHuman absorption, spray accuracy, dose-response, psychiatric efficacy, escalation and cycling have not been established.
ROUTE & DELIVERYIntranasal convenience is not evidence of brain exposure
Delivered micrograms depend on concentration and pump volume. The original PE-22-28 study cannot provide a human nasal conversion.
PROFESSIONAL SOURCE CONTEXT
No human dosing study availableThe source shows what has actually been studied. It does not validate the community example above or turn it into guidance.
No human PE-22-28 dose, pharmacokinetic profile, route comparison or treatment duration has been established.
No structured human dosing protocol has been added for this compound. That should not be interpreted as evidence for a community dosing schedule.
COMMUNITY DISCUSSION
Anecdotal / unvalidated · no human dose-finding trialWhat people commonly discuss
STARTING APPROACHES
Community protocol summaries often describe 100 mcg intranasally once daily as a cautious starting amount.
DURATION / CYCLES
Brief four-to-eight-week courses are discussed more often than indefinite use.
MAINTENANCE DISCUSSION
Some descriptions insert a two-to-four-week break, but no evidence-based washout or repeat-cycle interval exists.
Community patterns are anecdotal and unvalidated unless a linked human study independently supports the same approach.
CALCULATOR TOOLS
Work with the numbers
Convert amounts, concentration, liquid volume and vial requirements. These tools do the arithmetic; they do not select a dose.
NEED HELP READING THE NUMBERS?Source labels, routes and dose termsOpen guide +
HOW WE LABEL NUMBERSKnow where a dose came from before you compare it.
Authorised labelHuman trialCommunity-describedBEFORE THE NUMBERS: CHECK THE PRODUCT
Understand peptide testing →A dose only means something if the vial contains what the label says.
Purity, identity, quantity, sterility and endotoxin testing answer different questions. Learn how to read a COA and why a high purity percentage is not the same as confirming the amount in the vial.
READ THIS PAGE IN THREE STEPS
Understand the study before the number
A dose only makes sense alongside the population, route, frequency and duration. Start with where the number came from, then look at how it was delivered and how long the study actually ran.
1Source
Was it an authorised label, a human trial or a community-described pattern?
2Route & frequency
How was it given, and how often? The same number by a different route may not mean the same exposure.
3Duration
Was this one dose, a short trial or long-term treatment? A study window is not automatically a recommended cycle.
ROUTES EXPLAINED
Plain-English guideWhat do the injection types mean?
Route means how a compound was delivered. It affects absorption and can completely change how a study should be interpreted.
SubQ / SCSubcutaneous
An injection into the fatty layer just under the skin.
Common in peptide and metabolic-drug studies. It usually aims for systemic absorption rather than treating only the spot injected.IMIntramuscular
An injection into muscle tissue.
Muscle can absorb a medicine differently from fat. An IM amount should not be assumed to be equivalent to a SubQ amount.IVIntravenous
Delivered directly into a vein.
This gives immediate bloodstream exposure and is commonly used in supervised research or clinical settings. It is not interchangeable with a home injection route.INIntranasal
Delivered through the nose rather than by injection.
The amount delivered depends on formulation and device. A spray count alone does not tell you the dose unless concentration and spray volume are known.Other routes you may see:Oral = swallowed.Topical = applied to skin or another surface.Implant = a formulation placed under the skin by a trained professional.
CALENDAR SETUP
Eight-week editorial example
Community example · not clinically validatedThis is a subcutaneous community description. The peptide is preclinical; it cannot be treated as equivalent to intranasal descriptions or as an established human antidepressant regimen.
Form and route: Injection under the skin, as described in the example
| Calendar stage | Amount each time |
|---|---|
| Weeks 1–2 | 50 mcg |
| Weeks 3–4 | 100 mcg |
| Weeks 5–8 | 100 mcg |
Frequency: Every day · 1 entry per scheduled day.
The optional higher-dose extensions in the editorial description are omitted. This copy ends at eight weeks.
PLAIN-ENGLISH GLOSSARYWhat do the dose terms mean?Open glossary +
mgmilligram
One thousand micrograms (mcg).
mcg / μgmicrogram
One thousandth of a milligram.
mcg/kgweight-based dose
The amount is calculated for each kilogram of body weight.
IUinternational unit
A measure of biological activity used for some medicines; it cannot be converted to mg without compound-specific information.
Routehow it was given
For example SubQ, IM, IV, intranasal, oral or topical.
Frequencyhow often
For example once daily, twice weekly or every seven days.
Titrationplanned step-up or step-down
A protocol changes the amount over time rather than using one fixed amount throughout.
Half-lifehow quickly levels fall
The time taken for the amount of a compound in the body to reduce by roughly half. It can influence study timing but does not by itself define a schedule.
Cyclea defined period of use
Usually means an on-period followed by a stop or review. Many community 'cycles' have not been clinically validated.
Maintenancea continuing phase
A longer-term amount or interval used after an initial phase when a study or authorised treatment actually defines one.
Reconstitutionturning powder into solution
Adding a specified liquid to a freeze-dried vial so a concentration can be calculated.
U-100 unitssyringe volume markings
100 units equals 1 mL on a U-100 insulin syringe. The markings show volume, not peptide mass.
Often combined with
OFTEN COMBINED WITH
Community rationale · component roles · evidence boundaryWhy people explore pairings with PE-22-28
See the thinking behind community-named stacks, the different role each component is proposed to play, and how much of that idea has actually been tested as a combination.
Potential first, evidence in context. Pairings are usually explored because their research stories appear complementary. That makes them interesting to study, but does not yet prove extra benefit or safety.
CURRENT COMPOUNDPE-22-28
→
OFTEN EXPLORED WITHPE-22-28 + clinical mental-health care
PE-22-28 + Assessment, psychotherapy and/or prescribed treatment
→
OFTEN EXPLORED WITHPE-22-28 + Selank
PE-22-28 + Selank
→
OFTEN EXPLORED WITHPE-22-28 + Semax
PE-22-28 + Semax
Combination-specific human research is the strongest evidence for what a pairing adds. Evidence for either ingredient alone should not be silently transferred to the combination.
PPE-22-28 IS USUALLY DISCUSSED AROUNDTREK-1 blockade with preclinical mood and neurogenesis signals
＋PE-22-28 has a focused mouse-model story but no human psychiatric efficacy or safety programme.
PTHE PAIRED APPROACH MAY ADDEstablished mental-health care or another experimental nootropic
Clinical assessment and treatment address diagnosed symptoms; Selank or Semax add untested neuroactive uncertainty rather than proven synergy.
＋
OFTEN EXPLORED WITH
Explore →＋PE-22-28 + clinical mental-health care
PE-22-28 + Assessment, psychotherapy and/or prescribed treatmentWHY IT IS EXPLOREDPeople exploring mood effects may be trying to address symptoms that deserve a proper diagnosis and an evidence-based plan.
No study shows PE-22-28 improves standard care; it must not delay urgent help or replace established treatment.OFTEN EXPLORED WITH
Explore →＋PE-22-28 + Selank
PE-22-28 + SelankWHY IT IS EXPLOREDCommunity discussion pairs a TREK-1 mood hypothesis with a calmer-focus peptide narrative.
No human combination study establishes efficacy, interaction safety or dosing.OFTEN EXPLORED WITH
Explore →PE-22-28 + Semax
PE-22-28 + SemaxWHY IT IS EXPLOREDThe pairing is framed as mood-pathway plus neuroplasticity support.
Separate preclinical mechanisms do not establish cognitive or mood synergy, and overlapping CNS effects add uncertainty.01Protect urgent care
Suicidal thinking, severe agitation or mania-like change needs prompt professional help.
02Do not stack mechanisms
TREK-1 and neuroplasticity narratives are not combination evidence.
03Change one variable
Mood, sleep and cognition are hard to interpret when several CNS-active products start together.
Safety context
SAFETY & UNCERTAINTY
A neuroactive research peptide needs a mental-health safety boundary
01ENCOURAGING CONTEXTThe target and sequence are unusually specific
PE-22-28 has direct TREK-1 potency, selectivity and comparative preclinical data rather than only a broad nootropic narrative.
02THE IMPORTANT BOUNDARYMouse antidepressant tests are not human depression treatment
No participant-level mood outcome, pharmacokinetic study or clinical safety programme has been reported.
03WHAT REMAINS UNKNOWNNeuropsychiatric and long-term effects
Activation, sleep disruption, mania-like effects, suicidality, medication interactions, tolerance and repeated-course safety are uncharacterised.
What the current evidence saysNo human safety or interaction profile exists. New agitation, insomnia, impulsivity, mania-like symptoms, severe anxiety or suicidal thinking requires prompt clinical assessment; suicidal intent or immediate danger requires emergency help. Product identity and nasal delivery accuracy add separate risks.
01 · OBSERVEDPublished safety findings
The summary above reflects the human or preclinical evidence currently represented on this profile.
02 · UNCERTAINGaps still matter
Limited follow-up, small studies or absent controlled trials can leave uncommon and longer-term risks unresolved.
03 · CONTEXTProduct and regulatory status
Route, product identity, quality and regulatory status can materially change the safety context; see the linked status sources below.
Depression and major mood change require appropriate care; abrupt psychiatric-medication changes can be harmful.
Suicidal intent, severe agitation, impulsive risk-taking or mania-like symptoms need urgent professional or emergency support.
No validated human nasal exposure exists, while pump delivery, purity and contamination create separate risks.
Sources & current status
READ FURTHER
Sources & current status
Follow the professional sources used across this profile, then see how the compound is currently described in regulatory and research terms.
KEY RESEARCH RECORD
9 sourcesSources used on this profile
Original preclinical researchShortened spadin analogues: TREK-1 inhibition, stability and antidepressant activityFree full paper ↗Original publicationShortened spadin analogues: TREK-1 inhibition, stability and antidepressant activityJournal / DOI ↗Bibliographic recordShortened spadin analogues: TREK-1 inhibition, stability and antidepressant activityPubMed ↗Original preclinical researchSpadin establishes the sortilin–TREK-1 research conceptFree full paper ↗Original publicationSpadin establishes the sortilin–TREK-1 research conceptJournal / DOI ↗Bibliographic recordSpadin establishes the sortilin–TREK-1 research conceptPubMed ↗Trial registryHuman clinical-trial statusClinicalTrials.gov search ↗Professional sourceUnited KingdomMHRA products database ↗Professional sourceUnited StatesFDA Drugs@FDA database ↗
CURRENT STATUS
How to interpret its position today
No UK-authorised medicine is represented on this profile
PE-22-28 is presented as a research compound. The MHRA products database should be checked for any future change in authorised status.
MHRA products database ↗No FDA-approved therapeutic product identified
Regulatory evaluation of a substance for compounding is separate from approval of a drug for safety and efficacy.
FDA Drugs@FDA database ↗Profile reviewed against its linked source record on 20 September 2026. See how evidence is assessed.