What Is PE-22-28? The Fast-Acting Mood Peptide Explained

PE-22-28 works by blocking TREK-1, a potassium channel found in brain cells that helps control how easily neurons fire.

• TREK-1 and mood: mice bred without TREK-1 are resistant to depression-like behavior, which made the channel a drug target.
• Serotonin neurons: blocking TREK-1 increases the firing of serotonin-producing neurons.
• Neurogenesis: in mice, spadin and its analogs increased the formation of new neurons in the hippocampus, a marker linked to antidepressant response.

Spadin (2010). In mouse models of depression, spadin produced antidepressant-like effects after four days of treatment, compared with three to four weeks for fluoxetine, and increased new neuron formation.

PE-22-28 (2017). Djillani and colleagues tested shortened spadin analogs. PE-22-28 blocked TREK-1 more potently, lasted longer and produced antidepressant-like effects in mice, including after oral or intraperitoneal dosing in some tests. The researchers did not observe the heart or seizure side effects that some other TREK-1 drugs cause in mice.

Human data. There are no human trials of PE-22-28 or spadin. Reports of better mood or focus come from online anecdotes.

There is no human safety data. TREK-1 channels also exist in the heart, blood vessels and other tissues, and they help protect neurons during seizures and low oxygen. Blocking them in people could have effects that mouse studies did not reveal. Anyone with depression should work with a doctor rather than rely on an untested research chemical.

No. PE-22-28 is not FDA-approved, has never been tested in human trials and is not on the 503A Bulks List for compounding. In the U.S. it is sold only as a research chemical labeled “not for human consumption.”

PE-22-28 vs Selank. Both are discussed for mood, but Selank has clinical use in Russia for anxiety, while PE-22-28 has only mouse data.

PE-22-28 vs SSRIs. The appeal of TREK-1 blockers is speed: days instead of weeks in mice. Whether that holds in people is unknown.

Products sold as PE-22-28 by research suppliers are laboratory chemicals, not medicines. They are not made under drug manufacturing rules, so quality varies a lot between vendors. If you are evaluating a PE-22-28 supplier for lab research, these are the checks that matter:

• Batch-specific COA: the certificate should match the lot number on your vial, not a generic sample.
• Independent lab: testing should come from a named third-party lab, ideally with a way to verify the report online.
• Identity, not just purity: HPLC purity alone does not confirm the right molecule; look for mass spectrometry (MS) identity confirmation.
• Endotoxin and sterility results: these matter for any injectable research material.
• Correct fill amount: the measured content should be close to the labeled milligrams.

Our Trusted Sources page lists vendors we track, with current community codes. Our guide to reading a certificate of analysis explains each line of a COA.

• PE-22-28 is a 7-amino-acid analog of spadin that blocks the TREK-1 potassium channel.
• In mice it produced antidepressant-like effects within four days.
• It has never been tested in humans.
• TREK-1 exists in the heart and other tissues, so effects in people are unknown.
• It is not FDA-approved and is sold only as a research chemical.

What is PE-22-28?

PE-22-28 is a 7-amino-acid peptide derived from spadin that blocks the TREK-1 potassium channel. It showed antidepressant-like effects in mice.

Does PE-22-28 work for depression?

It has only been tested in mice, where it worked within days. There are no human trials.

Is PE-22-28 FDA-approved?

No. It has never been tested in humans and is sold only as a research chemical.

What is spadin?

Spadin is a 17-amino-acid fragment of the protein sortilin that blocks TREK-1. PE-22-28 is a shorter, more stable version of it.

Is PE-22-28 safe?

There is no human safety data. TREK-1 also exists in the heart and blood vessels, so blocking it could have unknown effects.

• Mazella et al. (2010), PLoS Biology – Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design
• Djillani et al. (2017), Frontiers in Pharmacology – Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity
• Heurteaux et al. (2006), Nature Neuroscience – Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype