Propeptide of neurotensin receptor 3 · PE-22-28
Natural antidepressant peptide — rapid mood improvement.
FDA
Research Only
WADA
Not Listed
HALF-LIFE
~Hours
ROUTE
Intranasal or SubQ injection
SCHEDULE
Daily
In Plain English
Natural antidepressant peptide — rapid mood improvement.
Status & Legality
What do these mean?Depression
Mood stabilization
TREK-1 inhibition
Neuroplasticity
Spadin is a natural peptide antidepressant derived from the propeptide of the neurotensin receptor sortilin. It works by blocking TREK-1 potassium channels — the same mechanism targeted by conventional antidepressants — but acts within days rather than weeks. Animal models show equal efficacy to fluoxetine with faster onset and no sexual side effects.
Limited human data
Mild nasal irritation (intranasal)
Generally well tolerated in animal models
Expecting immediate antidepressant effects — while faster than SSRIs, Spadin's mood effects build over 1–2 weeks of consistent use
Using aggressive doses without established safety data — limited human research means starting conservatively (200 mcg) is warranted
Using as the sole treatment for moderate-severe depression without addressing underlying factors — peptides work best as part of a comprehensive approach
SSRIs and SNRIs — may have additive TREK-1 inhibitory effects; proceed cautiously and monitor for overstimulation
Benzodiazepines — generally safe to combine; different mechanisms for mood and anxiety
Other peptide nootropics (Semax, Selank) — generally safe to stack; additive mood and cognitive support
Spadin is the most mechanistically interesting antidepressant peptide — it targets TREK-1, the same ion channel pathway as SSRIs, but with faster onset (days vs weeks) and no sexual side effects in animal models. Human data is very limited. The most promising use case is augmenting existing protocols rather than standalone replacement of proven antidepressant treatments.
SELANK
Anti-anxiety nootropic — calm focus without sedation.
SEMAX
Neuroprotective ACTH analog — focus, memory, and BDNF.
DIHEXA
7× more potent than BDNF — the strongest nootropic peptide.
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Stats
Sources & Studies
Mazella J. et al., PLoS Biol, 2010