PE-22-28: research
An experimental mood peptide studied in mice, with no human trials found.
Also called: PE 22-28, PE22-28, Mini-spadin, GVSWGLR.
Nootropic peptides · Shortened spadin analogue; experimental TREK-1 potassium-channel modulator · Evidence: Animal studies only.
Three PE-22-28 or mini-spadin papers studied mice or cells. Two studies of the longer peptide spadin give background; no human dosing study or registered trial was found.
Studies
- PE-22-28 in mice and cells. animal, Male C57BL/6J mice aged 7-9 weeks; engineered human-channel cells and cultured mouse neurons.. PE-22-28 changed mouse behavior and cell-growth markers; human benefit remains untested. (source)
- Mini-spadin after experimental stroke. animal, Mice after middle cerebral artery occlusion; sham-operated controls.. Mini-spadin affected recovery and mood-like behavior in stroke-injured mice. (source)
- Mini-spadin in insulin-making cells. in-vitro, Rat INS-1E pancreatic beta-cell cultures.. Mini-spadin protected cultured insulin-making cells; this is not evidence for diabetes treatment in people. (source)
- Parent spadin discovery. animal, Mice, rodent brain tissue and engineered cells; parent spadin, not PE-22-28.. Parent spadin linked TREK-1 inhibition to antidepressant-like effects in mice. (source)
- Parent spadin: assay-dependent effects. in-vitro, Frog eggs expressing mouse TREK-1 or TREK-2; parent spadin only.. Parent spadin effects depended on channel activation and experimental conditions. (source)
PE-22-28 dosage
Typical reported dose: 400 mcg once a day
- 400 mcg daily injection: 400 mcg once daily once daily, under the skin. Reported by users, rare report. Studied in: Adults posting personal use reports online; diagnosis and product identity unverified. (source)
- 200 mcg, 8 weeks on and 2 off: 200 mcg once daily once daily on treatment weeks, under the skin. Reported by users, rare report. Studied in: Adults posting personal use reports online; diagnosis and product identity unverified. (source)
- 300-600 mcg nasal report: Started at 300 mcg/day; later 600 mcg/day daily; distribution through the day not stated, nasal spray. Reported by users, rare report. Studied in: Adults posting personal use reports online; diagnosis and product identity unverified. (source)
- 400-1000 mcg on use days: 400-1000 mcg/day when used variable; some days skipped, nasal spray. Reported by users, rare report. Studied in: Adults posting personal use reports online; diagnosis and product identity unverified. (source)
- 160 mcg nasal blend, weekdays: 160 mcg PE-22-28 total per use day two sprays total daily, 5 days/week, nasal spray. Reported by users, rare report. Studied in: Adults posting personal use reports online; diagnosis and product identity unverified. (source)
- 800 mcg split-dose report: 400 mcg, then 400 mcg 6 hours later; one reported day two doses in one day, 6 hours apart, under the skin. Reported by users, rare report. Studied in: Adults posting personal use reports online; diagnosis and product identity unverified. (source)
These are doses reported in labels, trials or user reports, not a personal plan. Check the source behind each one.
PE-22-28 side effects and risks
Reported side effects
- Tiredness or excess sleep: User reports include tiredness after 400 mcg twice in a day; no reliable rate., moderate. Avoid driving if drowsy; seek review if symptoms persist. (source)
- Irritability, restless sleep or overstimulation: One 300 mcg injection report and one 200 400 mcg/day nasal report; no reliable rate., moderate. Stop PE-22-28 and seek review for persistent or worsening symptoms. (source)
- Nausea and poor concentration with phenelzine: One self report after 800 mcg intranasally; serotonin syndrome was not clinically confirmed., moderate. Stop the unapproved peptide and seek assessment; do not self-adjust prescribed antidepressants. (source)
- Worse mood or no improvement: A commenter reported feeling worse after about 3 weeks of 500 mcg injections. Frequency is unknown., moderate. Seek mental-health review; use urgent care for suicidal thoughts or inability to stay safe. (source)
- Allergy or infection from an unregulated product: General peptide product risks; PE 22 28 specific rates are unknown., serious. Seek immediate care for breathing problems; prompt care for spreading redness or fever. (source)
Stop and get help if
- Suicidal thoughts, a suicide plan, or inability to stay safe: Get urgent crisis help. In the US call 988; call 911 for immediate danger. Elsewhere use local emergency services.
- Confusion or agitation with fever, sweating, tremor or muscle jerks: Seek emergency care, especially with antidepressants or MAO inhibitors. PE-22-28-related serotonin toxicity is unproven.
- Trouble breathing, throat or tongue swelling, or collapse: Stop exposure and call emergency services now. Use prescribed emergency adrenaline if available.
- Spreading hot, painful redness or fever after an injection: Stop injections and seek prompt medical assessment for possible infection.
Who should avoid it
- pregnant: Precaution: fetal and pregnancy safety have not been studied in humans.
- breastfeeding: Precaution: transfer into milk and effects on a nursing infant are unknown.
- tryingToConceive: Precaution: human fertility and reproductive safety data are absent.
- under18: Precaution: no pediatric dosing or developmental safety evidence was found.
- depressionOrSuicidalThoughts: No human antidepressant trial supports replacing established care. New suicidal thoughts need urgent assessment.
- psychiatricCondition: Mood worsening and overstimulation appear in user reports. Psychiatric effects and drug interactions are unstudied.
- heartCondition: Precaution: TREK-1 has heart functions. A negative cell hERG test does not establish cardiac safety in people.
- seizureDisorder: Precaution: TREK-1 affects brain excitability. Human seizure risk is unknown.
- kidneyDisease: Precaution: human clearance and dose adjustment in kidney disease are unknown.
- liverDisease: Precaution: human metabolism and dose adjustment in liver disease are unknown.
- testedAthlete: The 2026 S0 rule covers unapproved pharmacological substances at all times.
- other: Avoid re-exposure after a serious allergic reaction to the product or its ingredients.
Interactions
- MAO inhibitors: No interaction trial. One phenelzine user reported nausea and poor concentration during PE-22-28 escalation; toxicity was not confirmed.
- SSRIs, SNRIs and other serotonin-active drugs: Possible additive brain effects are untested. Parent spadin increases serotonin-neuron firing in mice; a different mechanism does not prove compatibility.
- Insulin and sulfonylureas: Theoretical interaction: mini-spadin affects insulin-making cells in vitro. Human blood-sugar effects and low-sugar risk are unknown.
- Other brain-active peptides: Combinations are reported online without interaction or safety trials. Duplicate spadin analogues may also have different identities.
Product quality risks
- No peer-reviewed market-testing study of PE-22-28 products was found.
- General peptide warnings describe wrong amounts, unknown ingredients, microbes and endotoxin. PE-22-28-specific rates are unknown.
- A study of three online semaglutide samples found 28.56%-38.69% excess content and endotoxin in one. These are not PE-22-28 measurements.
How PE-22-28 works
TREK-1 is a channel that helps control how easily nerve cells fire. PE-22-28 can block it in lab tests. A mouse study also found channel activation at low doses, so its action is not simply more dose, more blockade. Human brain effects are unknown.
- TREK-1 / KCNK2: Blocks activated potassium currents in lab cells; low concentrations also activated resting currents in a later study.
- Brain-cell growth and connections: Mouse studies found more cell-division markers and connection-related proteins. This does not prove better human memory.
Half-life: Human half-life is unknown. The quoted 14-23 hours describes behavioral effects of modified analogues in mice, not PE-22-28 blood clearance.
Gaps: No human trial, dose-finding study, pharmacokinetic study or published dosing case report was found. No human dose has been studied. There is no human maximum to enter as studiedMax. The three direct papers share the originating research network; independent replication of PE-22-28 was not found. No reproductive, pregnancy, breastfeeding, pediatric or long-term human safety data was found. No validated nasal absorption, injection absorption, stability or sterile formulation data was found. Human adverse-event rates and interactions are unknown; forum reports cannot measure frequency or prove cause. Human studies of natural sortilin-propeptide blood levels did not administer PE-22-28. They are not dosing or efficacy trials. No dose-bearing peer-reviewed clinician protocol was found. A clinician review mentions the peptide without a dose. Microdose reports include 0.18-0.24 mg every few days, but the reporter did not confirm the route. Legal search results do not establish every national or local possession/import rule.
Related to PE-22-28
- Semax: A Russian nasal peptide with limited human evidence for brain and nerve effects.
- Selank: A Russian nasal anxiety peptide with uncertain long-term benefit and safety.
- Dihexa: An experimental memory compound with disputed animal research and no established human dose.
- P21: An experimental memory peptide with animal research and no established human dose or safety profile.
- Cerebrolysin: An injectable pig brain mixture with mixed stroke, brain-injury and dementia evidence.
Sources
- 21 CFR 216.23 — Bulk drug substances that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act., Office of the Federal Register · eCFR · 2026
- 503B Bulk Drug Substances List, FDA · FDA · 2026
- Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act, FDA · FDA · 2026
- Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act, FDA · FDA · 2026
- Cellulitis, NHS · NHS · 2026
- Medicines, European Medicines Agency · European Medicines Agency · 2026
- The 2026 Prohibited List, World Anti-Doping Agency · WADA · 2026
- Think twice before injecting peptides bought online: unauthorized products can seriously harm you, Health Canada · Health Canada · 2026
- Understanding your responsibilities when importing, compounding and supplying unapproved peptide products, Therapeutic Goods Administration · Therapeutic Goods Administration · 2026
- Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act, FDA · FDA · 2025
- Supply unlicensed medicinal products (specials), MHRA · 2025
- Anaphylaxis, NHS · NHS · 2023
- Drugs@FDA: FDA-Approved Drugs, US Food and Drug Administration
- Frequently Asked Questions About Suicide, National Institute of Mental Health
- Multifactor Quality and Safety Analysis of Semaglutide Products Sold by Online Sellers Without a Prescription: Market Surveillance, Content Analysis, and Product Purchase Evaluation Study., Ashraf AR et al. · Journal of medical Internet research · 2024
Sources checked: 2026-10-18.
Information only, not medical advice. Peptifacts does not sell anything and does not link to sellers.