Nootropic · 10mg × 10 vials
it's a peptide that unblocks the brain's mood pathway by closing a leak channel, and in animal work it acts as fast as ketamine without the dissociation.
PE 22-28 is a 7-amino-acid synthetic peptide derived from the propeptide of sortilin (positions 22-28 of the parent PE sequence), engineered by Mazella, Borsotto and colleagues at the Institut de Pharmacologie Moleculaire et Cellulaire as a shorter, more stable, more potent analog of spadin. It works by selectively inhibiting TREK-1 (TWIK-related potassium channel 1), a two-pore-domain K+ channel that, when overactive, dampens serotonergic neurotransmission in the dorsal raphe and prefrontal cortex. TREK-1 knockout mice are depression-resistant and show enhanced serotonin signaling, which is the genetic validation behind the whole drug class. By blocking TREK-1, PE 22-28 lifts the brake on serotonergic firing and downstream BDNF expression, producing rapid antidepressant-like effects in mice within 4 days (vs 3-4 weeks for fluoxetine) along with measurable hippocampal neurogenesis. In plain language: it's a peptide that unblocks the brain's mood pathway by closing a leak channel, and in animal work it acts as fast as ketamine without the dissociation. PE 22-28 is about 300-500x more potent at TREK-1 than spadin (IC50 ~0.12 nM vs 40-60 nM) with action duration extended from ~7 hours to ~23 hours.
Typical dose ranges by experience level - educational reference. Message us and we tailor it to you.
10 mg vial reconstituted to 5 mg/ml means 100 mcg = 0.02 ml = 2 IU on a U-100 syringe. Drip into one nostril (alternate nostrils daily). Beginners almost always report a smoother baseline mood and slightly more motivation within the first 2 weeks; the effect is subtle, not euphoric. Pair with consistent sleep and morning light, don't expect it to overcome lifestyle factors.
This is where most depression-targeted use lands. Stacking with Semax (700 mcg intranasal AM, separate dose 30 min apart) or Selank (300 mcg intranasal AM) is common and additive without receptor overlap. Subjective effect at this band is described as a "ceiling lift" on baseline mood, not stimulation. Sleep typically improves rather than worsens.
Advanced protocols often pair PE 22-28 with DSIP (sleep) or Selank (anxiolytic) for a mood + sleep + anxiety stack. Users with stubborn mood baseline (post-SSRI taper, post-burnout) sometimes report needing the full 500 mcg to feel the effect clearly. Off-cycles are mandatory at this dose to prevent TREK-1 receptor adaptation; community reports suggest the effect can blunt after 8+ continuous weeks.
Straight talk - what people actually report, and what the studies measured.
Peer-reviewed studies and clinical guidelines - tap any to read the source.
](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601071/) - founding paper, IC50 0.12 nM, FST immobility reduction, 4-day neurogenesis signal
Read study ↗PubMedShortened Spadin Analogs, PubMed 28955242same paper, PubMed entry, Mazella/Borsotto group
Read study ↗PubMedDjillani et al, Fighting against depression with TREK-1 blockers: Past and future, ScienceDirect 2018review on TREK-1 antidepressant strategy, spadin lineage, future directions
Read study ↗Physician commentaryDr. Elizabeth Yurth, Boulder Longevity Institute - PE 22-28 clinical protocol (400 mcg intranasal AM)](https://www.paragonsportsmedicine.com/peptides/pe-22-28) - first physician-published dosing protocol for human use
Read study ↗Physician commentaryJay Campbell, PE-22-28: The Antidepressant Peptidewidely-cited community-physician writeup on positioning vs SSRIs and ketamine
Read study ↗Physician commentaryRevolution Health & Wellness on PE-22-28 for mood, memory, neuroprotectionfunctional medicine clinic protocol context
Read study ↗Aggregated sentiment from public forums & socials - real-world reports, not individual endorsements.
Nasal irritation, dryness, mild congestion: most common, intranasal route - usually resolves with saline rinse and alternating nostrils
Mild headache: reported by a minority of users in first 3-5 days, usually resolves with continued dosing
Mild dizziness or lightheadedness: occasionally reported, especially at 400+ mcg, usually transient
Transient mood fluctuations: a small subset of users report an initial 2-3 day "blunting" before the effect kicks in
Sleep changes in early use: usually positive (deeper sleep) but a few users report vivid dreams or lighter sleep at higher doses
Injection site reactions (SubQ route): mild redness or soreness, less common than intranasal
Route: intranasal (community standard, leverages nose-to-brain transport) or SubQ
Storage: refrigerated, 14-21 days reconstituted; freeze the vial if not using within 3 weeks. Light sensitive, keep in original carton or wrap vial in foil.
Notes: Intranasal is preferred in community use because the peptide bypasses first-pass metabolism and the blood-brain barrier via the olfactory/trigeminal pathway. Use saline rinse before dosing for better mucosal absorption. Alternate nostrils to avoid drying. Morning dosing is standard (the literature mood effect mirrors a "wake-up lift" rather than sedation). PE 22-28 is fragile, do not shake the vial, swirl gently to mix. Plasma half-life is short (minutes) but central action persists ~21-23 hours, so once-daily dosing is sufficient.