Neuropeptide Y
One of the brain's most abundant peptides, tested once as a nasal spray in depression
Neuropeptide Y is a 36-amino-acid peptide released alongside noradrenaline by sympathetic nerves and widely present in the brain, where it drives feeding and damps the stress response. It is not a medicine. A single randomised trial has given it to people as a nasal spray.
What is it?
Neuropeptide Y is co-released with noradrenaline from sympathetic nerve endings and is one of the most abundant peptides in the brain. It acts on a family of receptors, Y1 to Y5, and the enzyme DPP-4 trims the full peptide, NPY1-36, into NPY3-36, which acts on different receptors and opposes some of its effects.
It was found in the human heart in 1983, in dense nerve fibres around the atrioventricular node and the coronary vessels, which added a peptide arm to the cholinergic and adrenergic nerves already known there.
In people it behaves as a stress peptide. In soldiers under acute stress, NPY release ran with cortisol and noradrenaline, and higher NPY went with less psychological distress. The one treatment trial, a nasal spray in major depression, found a short-lived improvement that had faded by the study's own main time point.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
These are the studies in people, read from their PubMed abstracts: one randomised trial, one stress study, one exercise study and one anatomical study.
A nasal spray tested in depression
Thirty people with major depression already on an antidepressant were randomised to insufflate 6.8 mg of NPY (12 people) or placebo (18). Depression scores improved against placebo at 5 and 24 hours, but at 48 hours, the trial's own primary time point, the difference was not significant.
Stress release tracks cortisol
In 25 active-duty personnel measured before, during and 24 hours after intense military training, NPY release ran positively with cortisol and with noradrenaline, and psychological distress during the stress ran negatively with NPY.
Exercise, and a shorter half-life than thought
Six healthy men exercised at moderate and heavy intensity in a randomised crossover study with saxagliptin or placebo. NPY1-36 rose with exercise intensity and fell more slowly than noradrenaline; NPY3-36 rose during recovery. The authors report that NPY1-36's half-life is considerably shorter than immunoassays had established.
A nerve peptide in the human heart
Dense NPY-containing nerve fibres were found in human heart tissue, at 22.1 pmol/g in the atrioventricular node and 19.6 pmol/g around the coronary vessels, in close contact with muscle fibres.
Side Effects & Contraindications
Reported Side Effects
From the one trial that gave it to people.
Contraindications & Cautions
Not a medicine.
Legal Status
NPY is not a medicine anywhere.
Frequently Asked Questions
?What does neuropeptide Y do?
It is released with noradrenaline by sympathetic nerves and is abundant in the brain, where it drives feeding and damps the stress response. It acts on the Y1 to Y5 receptors.
?Has it been given to people?
Yes, in research. A randomised trial gave 6.8 mg as a nasal spray to people with depression; improvement at 5 and 24 hours had faded by the 48-hour primary endpoint.
?Is it a stress or resilience peptide?
In soldiers under acute stress, higher NPY release went with less psychological distress. That is an association measured during stress, not evidence that giving NPY builds resilience.
?How long does it last in blood?
The 2022 exercise study reports that NPY1-36's half-life is considerably shorter than earlier immunoassay work suggested, without giving a figure for it.
References
- [pubmed] Mathé AA, et al. "A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder." Int J Neuropsychopharmacol, 2020;23(12):783-790. PMID: 33009815.
- [pubmed] Morgan CA 3rd, et al. "Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report." Biol Psychiatry, 2002;52(2):136-42. PMID: 12114005.
- [pubmed] Eugster PJ, et al. "Kinetics of neuropeptide Y, catecholamines, and physiological responses during moderate and heavy intensity exercises." Neuropeptides, 2022;92:102232. PMID: 35180646.
- [pubmed] Gu J, et al. "Neuropeptide tyrosine (NPY)--a major cardiac neuropeptide." Lancet, 1983;1(8332):1008-10. PMID: 6133058.
- [pubmed] Tatemoto K, et al. "Neuropeptide Y--a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide." Nature, 1982;296(5858):659-60. PMID: 6896083.
Sources & Citations
Studies were read from their PubMed abstracts on October 1, 2026; the US status was checked in Drugs@FDA the same day.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.