Days 1–3
The source reports subtle subjective changes; this is anecdotal, not measured.
Protocol / Research Dosing Guide
PE-22-28 Dosage Guide: Reported Figures, Reconstitution and Evidence Limits
An evidence-organized PE-22-28 reference that reports the circulating research conventions and flags the internal contradictions in them.
Last reviewed September 16, 202615 minute readResearch information only
Level 2 — Preclinical evidence onlyNo human trial or dose-finding studyNot FDA approved
PE-22-28 Quick Start
PE-22-28 is a shortened analogue of spadin, a peptide derived from the sortilin propeptide, studied in rodent models as a TREK-1 channel blocker with antidepressant-like effects. Every figure that circulates for it is a research convention extrapolated from animal work and community sources. The supplied source itself is internally inconsistent about both the amount and the receptor mechanism, which is a reason to treat its numbers as reported rather than established.
Why researchers care
Depression, anxiety and neuroplasticity research
Class
Synthetic spadin-derived peptide studied as a TREK-1 potassium channel blocker in preclinical antidepressant research
Route reported
Intranasal or subcutaneous in reported conventions
Cycle length
4–8 weeks as a reported convention
Regulatory status
Not FDA approved; no peer-reviewed human dose-finding trial
Loading supplier information
PE-22-28 Dosing Protocol and Schedule
The supplied source reports intranasal use of 500 mcg to 1 mg per nostril, one to two times daily, and subcutaneous use of 250 mcg as a conservative start and 500 mcg as a standard, once daily in the morning, over four to eight weeks. Elsewhere on the same page it states a 50 mcg subcutaneous standard, so the figures do not agree with each other.
| Phase or study | Amount | Frequency / evidence |
|---|---|---|
| Subcutaneous conservative start | 250 mcg once daily, 1–2 weeks then reassess | Reported convention |
| Subcutaneous standard | 500 mcg once daily, 4–8 weeks | Reported convention |
| Intranasal standard | 500 mcg – 1 mg per nostril, 1–2 times daily | Reported convention |
| Conflicting figure on the same source | 50 mcg subcutaneous once daily | Reported, contradicts the above |
| Cycle length | 4–8 weeks | Reported convention |
| Rest period | Not established | Not established |
These are not validated doses. The source contradicts itself by a factor of ten between its dosing table and its FAQ, and no peer-reviewed human dose-finding trial exists to resolve the difference.
PE-22-28 Supplies Needed
Neutral research-material planning only. This does not establish an appropriate amount or route.
Research planning item
Exact labeled research vial
Research planning item
Bacteriostatic water, commonly 2 mL for a 5 mg vial
Research planning item
A larger mixing syringe for the water draw
Research planning item
U-100 insulin syringes for subcutaneous arithmetic
Research planning item
A nasal atomizer if researching the intranasal format
Research planning item
Alcohol prep swabs and a sharps container
Research planning item
Refrigeration for the prepared vial
PE-22-28 Reconstitution Calculator
Vial-format concentration math
Concentration
2.5 mg/mL
Draw volume
0.2 mL
U-100 units
20
Mathematical draws
10
Arithmetic only. The entered amount is not a recommendation and does not establish suitability.
Best Time to Take PE-22-28: Morning or Night?
Morning or evening?
Morning is the reported convention, with late-day use associated anecdotally with difficulty sleeping.
Once or twice daily?
One to two times daily appears in the reported conventions.
With food?
Not applicable to the intranasal or subcutaneous formats.
Missed amount?
No validated procedure exists.
PE-22-28 Route Comparison
| Format | What is reported | Evidence limit |
|---|---|---|
| Intranasal | Described as the most common route for central targeting | No human absorption or exposure data |
| Subcutaneous | 250–500 mcg once daily in reported conventions | No human pharmacokinetic study |
| Oral | Not described as viable | No exposure data |
| Route conversion | Not established | The intranasal and subcutaneous figures are not interchangeable |
Routes and amounts are not interchangeable unless a verified study explicitly establishes a conversion.
PE-22-28 Half-Life and Dosing Frequency
| Measure | Finding | Evidence limit |
|---|---|---|
| Human half-life | Not established | No human pharmacokinetic study |
| Animal half-life | Not established as a published figure in the sources reviewed | Do not infer frequency |
| Frequency | Once or twice daily is a convention | Not pharmacokinetically derived |
| Repeat-cycle interval | Not established | No human data |
PE-22-28 Dosage Chart
| Route | Amount | Frequency | Source | Human validation |
|---|---|---|---|---|
| Subcutaneous | 250 mcg | Once daily, conservative start | Reported convention | No |
| Subcutaneous | 500 mcg | Once daily | Reported convention | No |
| Intranasal | 500 mcg – 1 mg per nostril | One to two times daily | Reported convention | No |
| Conflicting source figure | 50 mcg subcutaneous | Once daily | Reported, contradicts the table above | No |
Published study values describe those studies. Community-reported values are not validated dosing recommendations.
PE-22-28 Reconstitution Guide
Concentration: 2.5 mg/mL
| Entered amount | Volume | U-100 units |
|---|---|---|
| 0.5 mg | 0.2 mL | 20 units |
| 1 mg | 0.4 mL | 40 units |
| 1.5 mg | 0.6 mL | 60 units |
- 1.Confirm the labeled vial quantity, commonly 5 mg.
- 2.Clean the stopper with an alcohol swab.
- 3.Draw 2 mL of bacteriostatic water into a mixing syringe.
- 4.Inject it slowly down the vial wall to avoid foaming.
- 5.Swirl gently; never shake.
- 6.Allow about five minutes for full dissolution. 5 mg in 2 mL gives 2,500 mcg/mL.
- 7.At that concentration 250 mcg is 0.10 mL (10 units) and 500 mcg is 0.20 mL (20 units).
- 8.Label with the concentration and preparation date, then refrigerate at 2–8 °C and do not freeze the prepared solution.
Reconstitution does not establish identity, purity, sterility, stability, or an appropriate amount.
How PE-22-28 Works
Origin
PE-22-28 is a shortened analogue of spadin, itself derived from the sortilin propeptide.
PE-22-28 Human Trials and FDA Status
Current status · verified September 16, 2026
Not FDA approved; no peer-reviewed human dose-finding trial
- No peer-reviewed human clinical trial or dose-finding study of PE-22-28 was identified.
- The evidence base is preclinical rodent and in-vitro work on spadin and its shortened analogues.
- The supplied source assigns an evidence grade of C, preclinical data, and states there is no validated human dose.
- Claims of extreme potency relative to BDNF and of HGF/c-Met activity appear in the source without a cited primary study and should not be treated as established.
Who Should Avoid PE-22-28?
This is an evidence-gap and precaution list, not an approved prescribing label.
Pregnancy or breastfeeding
No safety data
Children or adolescents
No established protocol
A history of cancer
Listed as a precaution in the source on theoretical growth-signaling grounds
Psychiatric conditions or concurrent psychiatric medicines
No interaction data and no human evidence for an antidepressant effect
Anyone relying on the source's dosing figures
They contradict each other by a factor of ten
Long-term use
No human safety data
PE-22-28 Side Effects, Risks and Safety
Injection-site irritationReported
Important limitation: Mild, generic to the route.
Vivid dreamsCommonly reported anecdotally
Important limitation: No controlled incidence data.
Mild headache in the first daysReported
Important limitation: Anecdotal.
Difficulty sleeping with late-day useReported
Important limitation: The basis for the morning convention.
Dosing-error riskElevated
Important limitation: Small volumes and contradictory source figures increase the chance of error.
Human safety profileUnknown
Important limitation: No human clinical trial data.
PE-22-28 Timeline and Monitoring
Weeks 1–4
Reported subjective cognitive and mood changes with no controlled data behind them.
Weeks 4–8
The end of the reported convention block and a review point.
Monitoring
No validated monitoring schedule exists. The source suggests baseline and week-four basic, liver and kidney panels as a precaution given the absent safety data.
PE-22-28 Benefits and Results: What the Evidence Shows
| Claim | Evidence level | What research shows | Important limitation |
|---|---|---|---|
| Antidepressant-like effects | Animal research | Spadin and analogue rodent models | No human evidence |
| Neuroplasticity and neurogenesis | Animal research | Rodent model findings | No human evidence |
| Cognitive enhancement | Not established | Reported subjectively | No study supports this |
| Hair or cosmetic effects | Not applicable | The source explicitly states it is a CNS compound | Common misattribution |
PE-22-28 Storage and Handling
Sealed vial
Keep cool and dark per the product label.
Prepared vial
Refrigerate at 2–8 °C; the source reports a 30-day window, which is handling guidance rather than a verified stability study.
Freezing
The source advises against freezing the prepared solution.
Appearance
Cloudiness, discoloration or particles require qualified product review.
PE-22-28 Troubleshooting
The source gives two different doses
It does. The dosing table says 250–500 mcg and the FAQ says 50 mcg. Neither is validated; treat both as reported figures.
Draw is too small to measure
Use a larger water volume so the target lands on visible syringe marks.
Difficulty sleeping
Associated with later-day administration in anecdotal reports.
Intranasal and subcutaneous figures conflict
They are different routes with no established conversion.
Cloudy solution
Do not assume it is usable; seek qualified product guidance.
Expecting a validated protocol
None exists.
PE-22-28 Comparisons
| Compound | Class or mechanism | Evidence | FDA status |
|---|---|---|---|
| PE-22-28 | Spadin-derived TREK-1 blocker in preclinical research | Preclinical only | Not approved |
| Spadin | The parent sortilin-propeptide-derived peptide | Rodent antidepressant research | Not approved |
| P21 | CNTF-derived tetrapeptide acting via a BDNF cascade | Rodent studies only | Not approved |
| Semax | ACTH(4–7) analogue | Preclinical and limited clinical literature | Not FDA approved |
PE-22-28 Frequently Asked Questions
What is PE-22-28?
A synthetic shortened analogue of spadin, studied in preclinical antidepressant research as a TREK-1 potassium channel blocker.
Is it FDA approved?
No, and no peer-reviewed human dose-finding trial exists.
What amounts are reported?
250–500 mcg subcutaneously once daily, or 500 mcg to 1 mg per nostril intranasally, with a conflicting 50 mcg figure on the same source.
Why do the figures conflict?
The source's dosing table and FAQ disagree by a factor of ten. Without a human study there is nothing to resolve the difference.
What is the mechanism?
The published spadin literature describes TREK-1 blockade. The TrkB and HGF/c-Met descriptions in the supplied source are not supported by that literature.
What is its half-life?
Not established.
How is a 5 mg vial prepared?
Commonly with 2 mL of bacteriostatic water for 2,500 mcg/mL, making 500 mcg a 0.20 mL or 20-unit draw.
Is it a hair-loss peptide?
No. It is a central nervous system research compound and is frequently confused with unrelated cosmetic peptides.
What side effects are reported?
Anecdotally, injection-site irritation, vivid dreams, mild headache and sleep disruption with late-day use.
What does the calculator do?
Concentration and volume arithmetic only.
Sources and Research
Coverage source
1. PE-22-28 protocol coverage source
Reported dosing conventions, reconstitution math and timeline; internally inconsistent on amount and mechanism, and not primary evidence.
Open direct sourceAnimal research
2. Mazella et al., Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design
Foundational preclinical work on the parent peptide and TREK-1 blockade.
Open direct sourceAnimal research
3. Veyssiere et al., Retroinverso analogs of spadin display increased antidepressant effects
Rodent work on shortened and modified spadin analogues, the family PE-22-28 belongs to.
Open direct sourceAnimal research
4. Djillani et al., Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity
Direct preclinical characterization of the shortened analogue series including PE 22-28.
Open direct sourceMissing information flagged for review
- Any human trial, pharmacokinetics or toxicology: Not established
- A non-contradictory reported dose: Not established
- Confirmed receptor mechanism as described by the coverage source: Not established
- Half-life: Not established
- Validated cycle and rest period: Not established
- Compound-specific stability study and long-term safety: Not established