Overview
PE-22-28 is a synthetic 7-amino-acid peptide analogue of spadin designed as a rapid-acting, next-generation antidepressant and neurogenic compound.
What problem it targets: It targets treatment-resistant depression, acute depressive episodes, chronic stress-induced anhedonia, and sluggish neuroplastic response times.
What It Does
• Selectively blocks TREK-1 potassium channels: Inhibits the TREK-1 two-pore-domain potassium channel, a molecular target directly implicated in depressive pathology.
• Triggers rapid hippocampal neurogenesis: Induces the creation of new neurons and synapses in the hippocampus within 4 to 5 days, unlike standard SSRIs which take 4 to 6 weeks.
• Enhances serotonergic neurotransmission: Increases dorsal raphe nucleus 5-HT firing rates rapidly, lifting low mood and restoring reward processing.
• Realistic expectations: Preclinical studies show pronounced antidepressant-like responses within days. Investigated via intranasal or subcutaneous routes for rapid-onset cognitive and mood stabilization.
Reconstitution
| Vial size | BAC water / Solvent | Concentration |
|---|
| 5 mg | + 1 mL | 5 mg/mL |
| 10 mg | + 2 mL | 5 mg/mL |
Protocol
| Phase | Frequency | Dose | Units (2 mg/mL) | Notes |
|---|
| Weeks 1–4 | Daily | 250–500 mcg | 12.5–25u | SubQ or intranasal. Research-derived range; no validated human dose. |
| Off | 2–4 weeks | – | – | Cycle; neurogenic effects build over the on-period. Caution: entirely preclinical, no human trials, safety data, or approved dose. Doses are extrapolated from rodent studies (0.1–1 mg/kg). Included for completeness. Do not use in place of evaluated treatment for depression. By sex: Unisex experimental antidepressant peptide, animal data only, no sex-specific dosing. Avoid in pregnancy. |
Handling & Stacking
Injection site
SubQ abdomen, or intranasal. Rotate.
Storage
Freeze-dried: -4°F. Reconstituted: 36–46°F. Best used within 28 days, otherwise potency gradually fades over ~4 weeks (community estimate, no published data).
Side effects
Unknown in humans. Theoretically favorable (spadin lacks SSRI-type side effects in animals), but unverified.
What to expect
Unknown in humans. Animal data suggest rapid mood/neurogenesis effects, not demonstrated in people. Supply math 5mg → 2 vials | 10mg → 1 vial (4-wk @ 250 mcg/day, research-derived)
Pairs well with
Semax / Selank (mood + cognition); P21 (neurogenesis). All combinations unproven in humans
Avoid
Replacing prescribed antidepressant therapy. Bipolar disorder without supervision. Pregnancy
Safety & Patient Education
Contraindications
Pregnancy and lactation Use as a substitute for evaluated psychiatric care Hypersensitivity to the peptide
Warnings
No human safety, efficacy, or dosing data; entirely preclinical Mood disorders require proper evaluation, do not self-treat depression with a research peptide Bipolar/mania risk with any antidepressant mechanism, unknown here Quality varies, request a COA
Drug interactions
Other antidepressants / serotonergic agents: unknown combined effect Uncharacterized in humans
Labs
None established; psychiatric monitoring if used for mood
Stop criteria
Worsening mood, agitation, or any manic symptoms Any unexpected systemic reaction Suicidal thoughts, seek immediate care
Patient education
Promising mechanism but zero human data, treat as experimental Not a replacement for evaluated treatment of depression If you have a mood disorder, work with a clinician Seek immediate help for worsening mood or suicidal thoughts
References
PubMed · researchdosing · peptidedosages
