Educational reference only. Not medical advice. Consult a healthcare provider before starting any protocol.
PE-22-28
PE-22-28 (Spadin Analog, Sortilin Propeptide Fragment 22-28)
What it is
A synthetic heptapeptide (sequence: GVSWGLR) derived from amino acid positions 22-28 of the propeptide (PE) released during post-translational maturation of sortilin. PE-22-28 is a shortened analog of Spadin (PE 12-28) that retains full TREK-1 potassium channel inhibitory activity at approximately 333-500x greater potency. Discovered by the Mazella/Borsotto/Heurteaux group at CNRS/Université Côte d'Azur (France) as the shortest active degradation fragment of Spadin in mouse serum. All published research originates from this single laboratory group, and no human clinical data exists. Studied exclusively in rodent models and in vitro systems for antidepressant-like effects and, more recently, stroke neuroprotection.
Community-reported ranges
Dose values in mcg. Community-reported ranges sourced from biohacking forums and peptide vendor protocols. Animal study doses (3-4 μg/kg IP in mice) are not directly translatable to human dosing. No clinical dosing data exists. Not dosing guidance.
Reported dose range
50–400 mcg
Estimated half-life
Unknown (functional duration 14-23 hours in rodents)
Source: No formal PK study. Functional half-life estimated from duration of antidepressant behavioral effects in mice (Djillani et al., 2017). Standard PK parameters (Cmax, Tmax, clearance, bioavailability) have not been published for any species.
Reported cycle length
8–16 weeks on
4 weeks off
Route
intranasal, subcutaneous
Common vial sizes
8mg, 10mg, 20mg
Reported timing
AM
Reported frequency
Once daily
Frequently discussed alongside
Based on community forum discussions. Not a recommendation to combine compounds.
Selank
Both discussed in community forums for anxiolytic and mood-related peptide protocols
Semax
Discussed together as intranasal neuropeptides in nootropic communities
Cerebrolysin
Both studied for stroke recovery — PE-22-28 showed neuroprotective effects in preclinical stroke models
Noopept
Discussed alongside in neurogenesis and cognitive enhancement contexts
Published research
Published peer-reviewed research on PE-22-28 consists of two primary papers from a single French laboratory (CNRS/IPMC). Djillani et al. (2017) demonstrated antidepressant-like effects in mice across three behavioral paradigms at IC50 of 0.12 nM against TREK-1 — approximately 500x more potent than parent compound Spadin. Four-day treatment nearly doubled hippocampal neurogenesis (BrdU+ cells) and doubled PSD-95 expression. Pietri et al. (2019) showed PE-22-28 exhibited biphasic dose-dependent action: low doses activated TREK-1 (neuroprotective) while higher doses inhibited it (antidepressant), and was reported as superior to escitalopram in preventing post-stroke depression in mice. No independent replication exists. No human clinical trials have been conducted or registered.
Reported side effects
From community self-reports. Not from controlled studies.
No formal human safety data exists. Animal studies report no cardiac effects (no hERG channel inhibition), no increased seizure susceptibility, and no significant behavioral abnormalities. Community users have reported lethargy and sedation at higher doses (>600-800 mcg intranasal), irritability, and occasional sleep disruption. These reports are anecdotal and unverified.
Regulatory status
FDA (United States)
Not approved. No regulatory submission in any jurisdiction. Sold exclusively as a research chemical.
Health Canada
Not authorized as a therapeutic product. No DIN assigned. Not reviewed for safety or efficacy.
WADA (Competitive Athletes)
Not specifically named on the WADA Prohibited List. Likely falls under S0 (Non-Approved Substances) as it holds no governmental regulatory approval for human therapeutic use anywhere in the world.
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