A synthetic heptapeptide (7 amino acids) derived from Spadin, a naturally occurring antidepressant peptide. PE-22-28 is a shorter, more stable analog that retains the antidepressant and anxiolytic properties of Spadin. Works by blocking TREK-1 potassium channels in the brain.

Is PE-22-28 FDA approved?

No, PE-22-28 is not FDA approved. Current status: Preclinical - Animal studies only

What are the side effects of PE-22-28?

Reported side effects of PE-22-28 include: Limited safety data (preclinical only), Potential headache, Nasal irritation (intranasal use), Theoretical effects on cardiac TREK-1 channels, Unknown long-term effects, Not approved for human use.

What is the typical dosing for PE-22-28?

Doses from preclinical research. Common doses observed in research: 100-300 mcg intranasal, 100-500 mcg subcutaneous. Duration: Research protocols vary, often 2-4 weeks. Administration: Intranasal or subcutaneous injection.

Cognitive

PE-22-28

Also known as: PE22-28, Spadin Analog, TREK-1 Inhibitor Peptide

Preclinical

Popular For

Depression, anxiety, mood support, mental health

Key Facts: PE-22-28

Category: Cognitive
FDA Status: Not FDA Approved
Clinical Status: Preclinical - Animal studies only
Administration: Intranasal or subcutaneous injection
Typical Dose: 100-300 mcg intranasal or subcutaneous
Frequency: Once daily
Evidence Level: Animal Studies
Duration: Research protocols vary, often 2-4 weeks

Also Known As

PE22-28, Spadin Analog, TREK-1 Inhibitor Peptide

Mechanism of Action

PE-22-28 selectively blocks TREK-1 (TWIK-related potassium channel 1), a two-pore domain potassium channel highly expressed in the brain. TREK-1 inhibition increases neuronal excitability and enhances serotonergic and noradrenergic neurotransmission. This mechanism is distinct from traditional SSRIs and produces rapid-onset antidepressant effects in preclinical studies.

Research Summary

Animal studies demonstrate significant antidepressant and anxiolytic effects within days of administration (faster than traditional SSRIs which take weeks). PE-22-28 shows improved stability compared to full Spadin while maintaining efficacy. Research indicates potential for treatment-resistant depression. No human clinical trials conducted yet.

Clinical Status:Preclinical - Animal studies only

Trial Progress:Preclinical

Pre

III

FDA

Dosing Information

Animal Studies·Preclinical animal research only, no human trials

Note: Animal study doses may not translate directly to humans.

Typical DosingⓘDoses commonly used by people in practice, based on community reports and anecdotal experience.

Community experience

Common Dose

100-300 mcg intranasal or subcutaneous

Range

100-500 mcg per dose

Frequency

Once daily

Novel antidepressant peptide with rapid onset in animal studies. Works via TREK-1 channel inhibition, different from SSRIs. May be beneficial for treatment-resistant depression based on mechanism. Very limited human experience.

Research DosingⓘDoses from published scientific studies and clinical trials. May include human or animal research.

Scientific studies

Doses from preclinical research

Doses from Studies

100-300 mcg

Preclinical Research - Animal studies on TREK-1 inhibition ↗

Duration

Research protocols vary, often 2-4 weeks

Administration

Intranasal or subcutaneous injection

Timing & Administration

Best Time to Take

Morning

Once daily in research protocols

Food Recommendation

With or without food

Why This Timing?

May have activating effects. Morning dosing aligns with natural cortisol rhythm and avoids potential sleep interference.

Possible Side Effects

Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.

●Limited safety data (preclinical only)
●Potential headache
●Nasal irritation (intranasal use)
●Theoretical effects on cardiac TREK-1 channels
●Unknown long-term effects
●Not approved for human use

References

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