Endorphins (contracted from "endogenous morphine"[note 1]) are endogenous opioid neuropeptides and peptide hormones in humans and other animals. They are produced by the central nervous system and the pituitary gland. The term "endorphins" implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean "a morphine-like substance originating from within the body". The class of endorphins includes three compounds – α-endorphin, β-endorphin, and γ-endorphin – which preferentially bind to μ-opioid receptors. The principal function of endorphins is to inhibit the transmission of pain signals; they may also produce a feeling of euphoria very similar to that produced by other opioids.
Opioid neuropeptides were first discovered in 1974 by two independent groups of investigators:
- John Hughes and Hans Kosterlitz of Scotland isolated – from the brain of a pig – what some called "enkephalins" (from the Greek εγκέφαλος, cerebrum).
- Around the same time, in a calf brain, Rabi Simantov and Solomon H. Snyder of the United States found what Eric Simon (who independently discovered opioid receptors in vertebral brains) later termed "endorphin" by an abbreviation of "endogenous morphine", meaning "morphine produced naturally in the body". Studies have demonstrated that human and diverse animal tissues are capable of producing morphine, which is not a peptide.
Endorphins are naturally produced in response to pain, but their production can also be triggered by various human activities. Vigorous aerobic exercise can stimulate the release of β-endorphin, a potent μ-opioid receptor agonist, in the human brain, which contributes to a phenomenon known as a "runner's high". Laughter may also stimulate endorphin production; a 2011 study showed that attendees at a comedy club showed increased resistance to pain.
Endorphins are suspected to play a role in depersonalization disorder. The opioid antagonists naloxone and naltrexone have both been proven to be successful in treating depersonalization. Quoting a 2001 study involving the drug naloxone, "in  of 14 patients, depersonalization symptoms disappeared entirely, and  patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization."[non-primary source needed]
From the words ἔνδον / Greek: éndon meaning "within" (endogenous, ἐνδογενής / Greek: endogenes, "proceeding from within") and morphine, from Morpheus (Ancient Greek: Μορφεύς, translit. Morpheús), the god of dreams in the Greek mythology, thus 'endo(genous) (mo)rphine’.
- Stefano GB, Ptáček R, Kuželová H, Kream RM (2012). "Endogenous morphine: up-to-date review 2011" (PDF). Folia Biol. (Praha). 58 (2): 49–56. PMID 22578954.
Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. ... The apparently serendipitous finding of an opiate alkaloid-sensitive, opioid peptide-insensitive, µ3 opiate receptor subtype expressed by invertebrate immunocytes, human blood monocytes, macrophage cell lines, and human blood granulocytes provided compelling validating evidence for an autonomous role of endogenous morphine as a biologically important cellular signalling molecule (Stefano et al., 1993; Cruciani et al., 1994; Stefano and Scharrer, 1994; Makman et al., 1995). ... Human white blood cells have the ability to make and release morphine
- "μ receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. 15 March 2017. Retrieved 28 December 2017.
Comments: β-Endorphin is the highest potency endogenous ligand ... Morphine occurs endogenously .
- Goldstein A, Lowery PJ (September 1975). "Effect of the opiate antagonist naloxone on body temperature in rats". Life Sciences. 17 (6): 927–31. doi:10.1016/0024-3205(75)90445-2. PMID 1195988.
- Li Y, Lefever MR, Muthu D, Bidlack JM, Bilsky EJ, Polt R (February 2012). "Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins". Future Medicinal Chemistry. 4 (2): 205–226. doi:10.4155/fmc.11.195. PMC . PMID 22300099.
- "Is there a link between exercise and happiness?". Retrieved 18 September 2014.
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 7: Neuropeptides". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 183, 192. ISBN 9780071481274.
Different patterns of tissue-specific cleavage is another step by which a diversity of signaling peptides can be generated. Posttranslational processing can be illustrated by the cleavage and modification of proopiomelanocortin (POMC), the precursor of several peptides with distinct biological actions, including adrenocorticotropic hormone (ACTH), α-melanocytestimulating hormone (α-MSH; also called melanocortin), and β-endorphin.
- "Role of endorphins discovered". PBS Online: A Science Odyssey: People and Discoveries. Public Broadcasting System. 1 January 1998. Retrieved 15 October 2008.
- Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR (December 1975). "Identification of two related pentapeptides from the brain with potent opiate agonist activity". Nature. 258 (5536): 577–80. doi:10.1038/258577a0. PMID 1207728.
- Simantov R, Snyder SH (July 1976). "Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor". Proceedings of the National Academy of Sciences of the United States of America. 73 (7): 2515–9. doi:10.1073/pnas.73.7.2515. PMC . PMID 1065904.
- Poeaknapo C, Schmidt J, Brandsch M, Dräger B, Zenk MH (September 2004). "Endogenous formation of morphine in human cells". Proceedings of the National Academy of Sciences of the United States of America. 101 (39): 14091–6. doi:10.1073/pnas.0405430101. PMC . PMID 15383669.
- Kream RM, Stefano GB (October 2006). "De novo biosynthesis of morphine in animal cells: an evidence-based model". Medical Science Monitor. 12 (10): RA207–19. PMID 17006413.
- Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR (November 2008). "The runner's high: opioidergic mechanisms in the human brain". Cerebral Cortex. 18 (11): 2523–31. doi:10.1093/cercor/bhn013. PMID 18296435.
- Kolata, Gina (2008-03-27). "Yes, Running Can Make You High". The New York Times. ISSN 0362-4331. Retrieved 2016-05-26.
- Dunbar RI, Baron R, Frangou A, Pearce E, van Leeuwen EJ, Stow J, Partridge G, MacDonald I, Barra V, van Vugt M (March 2012). "Social laughter is correlated with an elevated pain threshold". Proceedings: Biological Sciences. 279 (1731): 1161–7. doi:10.1098/rspb.2011.1373. PMC . PMID 21920973.
- Nuller YL, Morozova MG, Kushnir ON, Hamper N (June 2001). "Effect of naloxone therapy on depersonalization: a pilot study". Journal of Psychopharmacology. 15 (2): 93–5. doi:10.1177/026988110101500205. PMID 11448093.
- Simeon D, Knutelska M (June 2005). "An open trial of naltrexone in the treatment of depersonalization disorder". Journal of Clinical Psychopharmacology. 25 (3): 267–270. PMID 15876908.