PE-22-28 common uses, half-life, side effects and more

PE-22-28 is a seven amino acid fragment of a longer peptide called spadin. Spadin is itself a piece of a propeptide the body releases when the sortilin receptor matures. Researchers found PE-22-28 by tracing how spadin breaks apart in blood and keeping the smallest piece that still acted on the target. Interest in it comes from studies of depression-like behavior in mice. Nobody has ever given it to a person in a registered study. No regulator has approved it anywhere. Vials sold online are research-market material.

• Depression and low mood
• Anxiety and stress resilience
• Motivation and task initiation
• Stroke recovery in animal research
• Laboratory tool for studying the TREK-1 channel

Once daily in short blocks by community practice

No study has established a dose in a person. Studies in mice used about 3 micrograms per kilogram injected into the abdomen for four days to produce the depression findings. A dose one hundred times smaller opens the channel instead of closing it and was used after an induced stroke. The same paper needed roughly 300 times more by mouth than by injection for a comparable effect. How it is given changes the amount needed by a wide margin. Nobody has tested the under-the-skin or nasal routes that sellers describe. Sites selling it list anywhere from 50 micrograms to 1 milligram a day with no human data behind any of it.

• Published studies injected it into the abdomen of mice or gave it by mouth and neither is a route people use
• Nothing has been tested by the under-the-skin or nasal routes that sellers describe
• The peptide sold online is the plain seven amino acid sequence rather than the stabilized version behind most of the duration data
• The 10 milligram vial that dosing guides build their protocols around appears only on those sellers' own pages

Nobody has measured how long PE-22-28 lasts in the blood of any animal. The 21 to 23 hour figure that circulates is not a blood measurement. It is how long a behavioral effect lasted in mice, measured on two chemically altered versions of the peptide at roughly ten times the usual dose.

• No side effect has been recorded in a person because no person has been given it in a study
• Animal testing found no change in heart function, seizure threshold, pain sensitivity, or blood sugar
• That testing covered the parent peptide rather than this fragment and ran three weeks at most
• Studies of the fragment in mice report no adverse findings and were not designed to look for them

PE-22-28 acts on a potassium channel called TREK-1 that helps hold nerve cells at rest. Mice bred without that channel behave as though already on an antidepressant. The peptide's effect on the channel reverses with dose. Low doses open it and higher doses close it. An independent laboratory tested the parent peptide and found it does not close the channel at rest, does not close it once something else has opened it, and only blunts opening when applied first. Those authors describe it as binding the shut channel rather than blocking an open one. Nobody has shown in a living animal that the behavioral effects run through this channel.

Nobody has given PE-22-28 to a person in any registered study. That the parent peptide acts on TREK-1 is confirmed by many laboratories across several countries and in tissues the original group never touched. One of them bought the peptide commercially and found it works only under a narrow assay condition. That condition is the one the headline potency figure was measured under. The depression side is thinner. Independent tests of the behavior come from a small number of Chinese laboratories using one stress model. The founding claim that removing the channel makes mice depression-resistant has never been independently retested either way. A separate laboratory retested a different claim about the same knockout mice and could not reproduce it. All of the behavioral studies use rodent despair tests rather than a model of human depression.

• Nobody has taken PE-22-28 in a study and nothing is known about what it does in people
• The target channel sits in heart muscle where independent work links it to atrial fibrillation and ventricular arrhythmia
• Animal heart testing covered only a resting heart and not the stretched or diseased conditions where that channel matters most
• Blocking the channel in human lung blood vessel cells produced an electrical pattern resembling pulmonary hypertension
• Mice bred without the channel are more prone to seizures and the one drug study that tested this found no change
• Anti-doping rules do not name it and the catch-all clause covering unapproved substances reaches it