Overview
PE-22-28 is a cognitive-focused compound. Heptapeptide fragment derived from DSIP (Delta Sleep-Inducing Peptide).
With a half-life of ~24 minutes, PE-22-28 requires daily administration in most observed protocols. Administered via nasal and SubQ injection, it has a bioavailability of approximately 60% via its primary route.
Estimated half-life approximately 20–30 minutes. Supports nasal and subcutaneous administration routes. Limited published human pharmacokinetic data. One-compartment model.
Mechanism of Action
PE-22-28's pharmacological activity involves the following key pathways:
Neurotrophin Modulation
PE-22-28 interacts with central nervous system pathways involved in neuroplasticity and cognitive function.
CNS Penetration
PE-22-28 reaches the central nervous system via intranasal administration, bypassing the blood-brain barrier.
Dosing Protocols
The following protocols represent commonly observed dosing patterns. These are observational summaries, not recommendations.
Dose
100 mcg/day
Route
Intranasal
Frequency
2-3 times daily
Duration
4-12 weeks
Dose
500 mcg/day
Route
Intranasal
Frequency
2-3 times daily
Duration
4-12 weeks
Reconstitution Steps
PE-22-28 is supplied as a lyophilized (freeze-dried) powder and requires reconstitution before use. Common vial sizes: 5 mg, 10 mg.
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1
Gather Supplies
You will need your PE-22-28 lyophilized vial (typically 5 mg or 10 mg), bacteriostatic water for injection, an insulin syringe (100-unit), and alcohol swabs. Because doses are in the microgram range, precise reconstitution volume is important.
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2
Swab and Prepare
Wipe the rubber septum of both the PE-22-28 vial and the bacteriostatic water vial with a fresh alcohol swab. Allow both to air-dry for 10–15 seconds before inserting any needles.
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3
Draw Bacteriostatic Water
For a 10 mg vial, draw 3 mL of bacteriostatic water, yielding a concentration of approximately 3.33 mg/mL (3,330 mcg/mL). This concentration makes it practical to measure sub-100 mcg doses with a standard insulin syringe.
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4
Add Water to Vial
Angle the needle so water flows gently down the inside glass wall of the vial onto the powder. Avoid directing the stream forcefully onto the peptide cake to prevent foaming and degradation.
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5
Swirl Gently to Dissolve
Roll the vial slowly between your palms until the powder is fully dissolved and the solution appears clear. Do not shake. PE-22-28 is a small, water-soluble peptide and typically dissolves readily.
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6
Label and Refrigerate
Label with the date reconstituted and concentration. Store in the refrigerator at 2–8°C and use within 4 weeks. For intranasal use, draw the desired volume into a nasal atomiser device using the same syringe technique.
Quick Reconstitution Math
10 mg vial + 3 mL bac water = 3,330 mcg/mL. For a 100 mcg dose, draw approximately 3 units on a 100-unit insulin syringe. For a 200 mcg dose, draw approximately 6 units. Use the Milligram reconstitution calculator for custom vial sizes.
Lyophilized vials stable at 2–8°C for 2+ years. Reconstituted solution stable refrigerated at 2–8°C for up to 4 weeks. Keep away from light and do not freeze the reconstituted vial.
Frequently Asked Questions
What is PE-22-28 and how does it work?
PE-22-28, also called Mini-Spadin, is a synthetic 7-amino-acid peptide derived from the naturally occurring peptide Spadin. Its primary mechanism is selective inhibition of TREK-1 (KCNK2) two-pore domain potassium channels – blocking these channels depolarises neurons and increases excitability of serotonergic pathways, resulting in elevated monoamine neurotransmission. Research has also identified activity at TrkB receptors (the BDNF receptor), suggesting a parallel neuroplasticity-supporting effect. PE-22-28 is an optimised analog with approximately 300-fold greater potency than the parent Spadin molecule.
What is the half-life of PE-22-28 and how often should it be dosed?
PE-22-28 demonstrates a significantly improved duration of action compared to its parent compound Spadin. Published research reports an action duration of up to approximately 23 hours for PE-22-28 versus approximately 7 hours for Spadin, with in vivo half-life studies indicating multi-hour plasma stability. Once-daily dosing is the standard community approach based on this pharmacokinetic profile, with subcutaneous administration in the morning commonly reported.
How long does PE-22-28 take to show mood or cognitive effects?
In preclinical models, antidepressant-like effects and increases in hippocampal neurogenesis markers were observed within 4 days of administration – a notably faster timeline than conventional antidepressants. Community reports of mood stabilisation and reduced anxiety are typically noted within the first 1–2 weeks. Cognitive improvements such as enhanced focus and memory clarity are generally reported over 4–8 weeks of consistent use.
What are the commonly reported effects of PE-22-28?
The most frequently reported community observations include improved mood, reduced anxiety, enhanced mental clarity, and greater emotional resilience. Some users report improved memory formation and recall alongside the mood-related effects. These observations are consistent with the compound's dual mechanism across serotonergic pathways (via TREK-1 inhibition) and neuroplasticity pathways (via TrkB). All available human data is anecdotal – no published clinical trials in humans have been completed.
How is PE-22-28 administered – nasal or subcutaneous?
PE-22-28 is most commonly administered via subcutaneous injection or intranasal delivery. Subcutaneous injection is the primary route reported in research contexts, with typical doses of 100–300 mcg once daily. Intranasal administration is also observed in community protocols due to the ease of delivery and the peptide's small size supporting mucosal absorption, though bioavailability data for the nasal route specifically is limited. Research confirms activity across multiple administration routes including intravenous, subcutaneous, and oral.
How does PE-22-28 compare to Spadin?
PE-22-28 was designed specifically to improve on Spadin's limitations. It demonstrates approximately 300-fold greater TREK-1 inhibitory potency (IC50 ~0.12 nM versus ~40–60 nM for Spadin), a duration of action up to 23 hours compared to Spadin's ~7 hours, and significantly improved in vivo stability. These pharmacokinetic improvements were the primary motivation for developing the PE-22-28 analog and are why it is the preferred form used in subsequent research.