Peptides, small chains of amino acids, play a significant role in regulating your mood and are being studied as a promising area for novel treatments of depression. If an amino acid is a pearl, and the pearl necklace is a protein, a peptide is a modest cluster of the pearls, not 50 pearls or amino acids (that size is a protein).
Research using brain imaging techniques has helped identify how specific peptides influence emotional regulation and has even uncovered distinct biological subtypes of depression.
Supporting that there is not one cause or type of depression. We discuss this in exciting detail in our powerful book, Destroy Depression: Return to Joy ( Jan. 30, 2026)
We mention PE 22–28 as an antidepressant peptide with some research support in this book merely to raise the option.
OTHER SAMPLE MOOD AND DEPRESSION PEPTIDES
Peptides and Mood Regulation
Neuropeptides act as signaling molecules in the brain, influencing emotions, motivation, and the stress response.
- Hypocretin: Levels of this peptide were found to be greatly increased when subjects were happy and decreased when they were sad. Boosting hypocretin may help elevate mood and alertness. The absence of this peptide appears to cause most narcolepsy (Latorre). This is a very strong peptide that should be carefully pondered in the future, depending on your country.
- And Ten-Blanco summarizes rodent studies that are of uncertain application. While significant stress causes depression in rats and mice, it is only a contributing factor in humans, as our Destroy Depression text shows. So you see some promote a peptide and there is no harm reading about it.
- Melanin Concentrating Hormone (MCH): MCH is linked to sleep, with high levels during rest. Antagonism of MCH has shown antidepressant-like effects in some studies.
- Neuropeptide Y (NPY): NPY helps regulate anxiety and stress responses.
- Oxytocin: Known as a key factor in social bonding, trust, and empathy, oxytocin has anxiolytic (anti-anxiety) effects and can help with emotion regulation.
- GLP-1 (Glucagon-like peptide-1): This gut peptide is being explored as a potential treatment target for depression, as it may improve mood and cognitive decline associated with the condition. As we discuss in our book, 100 trillion gut bacteria are impacting the brain. And these treatments have vast actions including lowering inflammation in many pathways.
- Kupkova (referenced below) lists over 10 peptides with antidepressant action. It seems researchers do not have the same list.
Zhang (referenced below) is one of many with an interest in food-derived peptides by improving a pro-mood interaction between the brain and the 100 trillion bacteria in the gut that function like an organ. I have started an antibiotic peptide book to kill Bartonella, Lyme, their biofilms and other infections. In a month it is exploding in options to study. The same thing is happening with depression peptides.
Though getting immensely expensive research is hard on each one. Though often some exist. The INTERNATIONAL PEPTIDE SOCIETY has large research monographs von about 100 peptides.
Brain imaging, particularly functional MRI, PET scans, and SPECT scans may allow the detection of peptide brain effects–especially PET and SPECT.
Recent research has used advanced brain imaging and AI to identifysix distinct types of depression.
Peptide Therapy as an Emerging Frontier
Peptide therapy is promising, though largely off-label and not yet FDA-approved to treat depression. Common peptides used are Thymosin Alpha-1 and Selank for mood enhancement and anti-anxiety effects.
While generally considered safe, these medications can have an impact on mood, with some patients experiencing a boost in mood and others struggling with increased depression or irritability, which requires close care. There is no set dose for anyone.
Sample Sources
Peptide CME 40.5 hours CME Peptide Certification Two Conferences. George Washington Medical. (Misc. ideas in blog)
https://www.psychologytoday.com/us/blog/the-shameless-psychiatrist. Accessed December 28, 2025. (peptide options, etc.)
https://www.columbiapsychiatry.org/research/research-areas/ (Imaging topic)
https://med.stanford.edu/news/all-news/2024/06/depression-biotypes.html# (Six subtypes of depression)
Kupcova, I.; Danisovic, L.; Grgac, I.; Harsanyi, S. Anxiety and Depression: What Do We Know of Neuropeptides? Behav. Sci. 2022, 12, 262. https://doi.org/10.3390/ bs12080262 (Over 10 antidepressant peptides and not the same as in other articles).
Yan Zhang, Yujia Lu, Yuchen Zhao, Wei Wu, Na Zhang, Yuhao Zhang, Yu Fu, The potential of food-derived peptides in alleviating depressed mood: Function, evaluation and mechanism, Food Research International, Vol 211, 2025, 116520, https://doi.org/10.1016/j.foodres.2025.116520.
Latorre D, Kallweit U, Armentani E, Foglierini M, Mele F, Cassotta A, Jovic S, Jarrossay D, Mathis J, Zellini F, Becher B, Lanzavecchia A, Khatami R, Manconi M, Tafti M, Bassetti CL, Sallusto F. T cells in patients with narcolepsy target self-antigens of hypocretin neurons. Nature. 2018 Oct;562(7725):63-68. doi: 10.1038/s41586-018-0540-1. Epub 2018 Sep 19. PMID: 30232458.
Ten-Blanco M, Flores Á, Cristino L, Pereda-Pérez I, Berrendero F. Targeting the orexin/hypocretin system for the treatment of neuropsychiatric and neurodegenerative diseases: From animal to clinical studies. Front Neuroendocrinol. 2023 Apr;69:101066. doi: 10.1016/j.yfrne.2023.101066. Epub 2023 Apr 2. PMID: 37015302.