Neuropeptide Y (NPY)
Evidence: CCognitive / Neuro
Evidence Snapshot
What this grade covers
Human administration data include controlled physiology studies and small randomized psychiatric trials. Therapeutic efficacy remains preliminary and unreplicated.
Regulatory Context
Neuropeptide Y (NPY) is an endogenous human neuropeptide studied in research and small controlled human trials; it is not an FDA-approved drug. No subject-specific FDA regulatory action has been identified in the current source set, and the absence of FDA approval does not itself indicate that NPY is unsafe.
Research Takeaway
Mature Neuropeptide Y is a distinct product of the human pro-NPY precursor, which also gives rise to the separate C-flanking peptide CPON.
Evidence boundary: CPON, PYY, and pancreatic polypeptide are not aliases or interchangeable evidence sources for NPY.
See all 6 evidence claims →Quick Summary
Neuropeptide Y (NPY) is a mature 36-amino-acid human neuropeptide produced from the pro-NPY precursor, distinct from the co-produced peptide CPON as well as from the related family peptides PYY and pancreatic polypeptide. Controlled human studies have administered NPY intranasally and intravenously, producing measurable vascular, adrenergic, and systemic effects, and small randomized trials have reported short-term symptom signals in PTSD and major depressive disorder. These early clinical signals are preliminary - one trial's primary endpoint was not met - and do not establish NPY as an effective treatment.
Mechanism & Research Overview
Human NPY administration influences vascular tone (splanchnic and renal vasoconstriction) and potentiates alpha-1-adrenergic pressor responses, demonstrating systemic autonomic/vascular signaling. Small randomized trials in PTSD and major depressive disorder found short-term symptom signals after intranasal NPY, though the MDD trial's prespecified 48-hour primary endpoint was not significant, and the PTSD trial was a small single-ascending-dose design - these findings are preliminary and require replication before any therapeutic conclusion is drawn.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Mature Neuropeptide Y is a distinct product of the human pro-NPY precursor, which also gives rise to the separate C-flanking peptide CPON.
Does not establish
Evidence boundary: CPON, PYY, and pancreatic polypeptide are not aliases or interchangeable evidence sources for NPY.
Sources: NPY - Pro-neuropeptide Y - Homo sapiens (Human)
Supported
Exact NPY has been administered to humans by intranasal and intravenous routes in controlled research, producing measurable systemic and vascular effects.
Does not establish
Evidence boundary: These studies establish human pharmacology, not broad therapeutic benefit.
Sources: Intranasal administration of neuropeptide Y in man: systemic absorption and functional effects; Splanchnic and renal vasoconstriction during neuropeptide Y infusion in healthy humans; Human neuropeptide Y potentiates alpha1-adrenergic blood pressure responses in vivo
Supported
Small randomized clinical studies have reported short-term symptom signals after intranasal NPY in PTSD and major depressive disorder.
Does not establish
Evidence boundary: The PTSD study was small and dose-ranging; the MDD study did not meet its prespecified 48-hour primary endpoint. These findings are preliminary and do not establish NPY as an effective treatment for PTSD or depression.
Sources: A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder; A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder
Supported
Human NPY administration can influence vascular tone and adrenergic pressor responses.
Does not establish
Evidence boundary: Vascular pharmacology does not establish psychiatric or metabolic treatment efficacy.
Sources: Splanchnic and renal vasoconstriction during neuropeptide Y infusion in healthy humans; Human neuropeptide Y potentiates alpha1-adrenergic blood pressure responses in vivo
Supported
Controlled human studies demonstrate that NPY can have systemic physiological effects, so route, dose, and cardiovascular context materially affect interpretation of tolerability data.
Does not establish
Evidence boundary: Small research studies cannot establish chronic-use safety.
Sources: Intranasal administration of neuropeptide Y in man: systemic absorption and functional effects; Splanchnic and renal vasoconstriction during neuropeptide Y infusion in healthy humans; Human neuropeptide Y potentiates alpha1-adrenergic blood pressure responses in vivo; A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder
Supported
No specific regulatory conclusion is frozen beyond neutral investigational status until an official source is supplied.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
NPY has produced measurable splanchnic/renal vasoconstriction and potentiated adrenergic pressor responses in controlled human studies.Safety Consideration
Small randomized trials in PTSD and major depressive disorder reported short-term symptom changes, but the MDD trial's primary endpoint was not met and neither trial establishes efficacy.Safety Consideration
All available human evidence comes from small, single- or short-dose experimental studies; long-term safety has not been established.
Research Areas Being Studied
Research areas discussed on this page reflect the Cognitive / Neuro category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder (2020):
- A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder (2018):
- Human neuropeptide Y potentiates alpha1-adrenergic blood pressure responses in vivo (1998):
- Intranasal administration of neuropeptide Y in man: systemic absorption and functional effects (1996):
- Splanchnic and renal vasoconstriction during neuropeptide Y infusion in healthy humans (1992):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder | 2020 | 30 MDD patients; randomized double-blind NPY 6.8 mg vs placebo added to stable antidepressant therapy | NPY showed greater MADRS improvement than placebo at 5 and 24 hours, but the prespecified 48-hour primary endpoint was not significant. | ||
| A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder | 2018 | 26 participants with PTSD; randomized double-blind crossover single ascending intranasal NPY doses vs placebo | The study evaluated tolerability and acute anxiolytic effects after trauma-script provocation across NPY doses. | ||
| Human neuropeptide Y potentiates alpha1-adrenergic blood pressure responses in vivo | 1998 | 12 healthy volunteers; single-blind crossover human NPY plus phenylephrine | Subpressor human NPY potentiated alpha1-adrenergic pressor responses, demonstrating systemic vascular interaction in vivo. | ||
| Intranasal administration of neuropeptide Y in man: systemic absorption and functional effects | 1996 | 7 healthy volunteers; double-blind randomized controlled intranasal NPY dose study | Intranasal NPY was systemically absorbed and produced measurable functional effects in healthy humans. | ||
| Splanchnic and renal vasoconstriction during neuropeptide Y infusion in healthy humans | 1992 | 6 healthy subjects; intravenous escalating NPY infusion | NPY produced splanchnic and renal vasoconstrictor effects in humans. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| NPY - Pro-neuropeptide Y - Homo sapiens (Human) | Homo sapiens curated identity record | Human pro-NPY precursor, cleaved into mature NPY and CPON. | No source link available |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published and official research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-08-24.
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