Chemical structure of alpha-Neoendorphin (α-Neoendorphin)
Endorphins (“endogenous morphine”) are endogenous opioid peptides that function as neurotransmitters.[1] They are produced by the pituitary gland and the hypothalamus in vertebrates during exercise,[2] excitement, pain, consumption of spicy food, love and orgasm,[3][4] and they resemble the opiates in their abilities to produce analgesia and a feeling of well-being. The term 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.”[5] The term “endorphin rush” has been adopted in popular speech to refer to feelings of exhilaration brought on by pain, danger, or other forms of stress,[2] supposedly due to the influence of endorphins. When a nerve impulse reaches the spinal cord, endorphins that prevent nerve cells from releasing more pain signals are released.



Opioid neuropeptides were first discovered in 1974 by two independent groups of investigators:
  • Around the same time, in the calf brain, Rabi Simantov and Solomon H. Snyder of the United States found[8] what Eric Simon (who independently discovered opioid receptors in the brain) later termed “endorphin” by an abbreviation of “endogenous morphine”, meaning “morphine produced naturally in the body”.[5] Importantly, recent studies have demonstrated that diverse animal and human tissues are in fact capable of producing morphine itself, which is not a peptide.[9][10]

Mechanism of action

Chemical structure of beta-endorphin
Beta-endorphin (β-Endorphin) is released into blood from the pituitary gland and into the spinal cord and brain from hypothalamic neurons. The β-endorphin that is released into the blood cannot enter the brain in large quantities because of the blood–brain barrier, so the physiological importance of the β-endorphin that can be measured in the blood is far from clear. β-Endorphin is a cleavage product of pro-opiomelanocortin (POMC), which is also the precursor hormone for adrenocorticotrophic hormone (ACTH). The behavioural effects of β-endorphin are exerted by its actions in the brain and spinal cord, and it is presumed that the hypothalamic neurons are the major source of β-endorphin at these sites. In situations where the level of ACTH is increased (e.g., Cushing’s Syndrome), the level of endorphins also increases slightly. β-Endorphin has the highest affinity for the μ1 opioid receptor, slightly lower affinity for the μ2 and δ opioid receptors, and low affinity for the κ1 opioid receptors. μ-Opioid receptors are the main receptor through which morphine acts. In the classical sense, μ opioid receptors are presynaptic, and inhibit neurotransmitter release; through this mechanism, they inhibit the release of the inhibitory neurotransmitter GABA, and disinhibit the dopamine pathways, causing more dopamine to be released. By hijacking this process, exogenous opioids cause inappropriate dopamine release, and lead to aberrant synaptic plasticity, which causes dependency. Opioid receptors have many other and more important roles in the brain and periphery however, modulating pain, cardiac, gastric and vascular function as well as possibly panic and satiation, and receptors are often found at postsynaptic locations as well as presynaptically.


Scientists sometimes debate whether specific activities release measurable levels of endorphins. Much of the current data comes from animal models which may not be relevant to humans. The studies that do involve humans often measure endorphin plasma levels, which do not necessarily correlate with levels in the central nervous system. Other studies use a blanket opioid antagonist (usually naloxone) to indirectly measure the release of endorphins by observing the changes that occur when any endorphin activity that might be present is blocked.

Runner's high

A publicized effect of endorphin production is the so-called “runner's high”, which is said to occur when strenuous exercise takes a person over a threshold that activates endorphin production. Endorphins are released during long, continuous workouts, when the level of intensity is between moderate and high, and breathing is difficult. This also corresponds with the time that muscles use up their stored glycogen. During a release of endorphins, the person may be exposed to bodily harm from strenuous bodily functions after going past his or her body's physical limit. This means that runners can keep running despite pain, continuously surpassing what they otherwise would consider to be their limit. Runner's high has also been known to create feelings of euphoria and happiness. Runner's high has been suggested to have evolutionary roots based on the theory that it helped with the survival of early humans. Runner's high allows humans to run for vast lengths without pain.[citation needed] Most early humans hunted and gathered for their food. This required them to cover long distances hunting down their prey or foraging for their food. This could have caused them to develop conditions such as shin splints and stress fractures in their shin and feet bones. Without runner's high to negate the pain caused by running on bones with these conditions, early humans theoretically would not have been able to repeatedly cover these vast distances in search of their food and thus would have starved. Current African tribes make use of runner's high when conducting persistence hunting (a method in which tribesman hunt an animal and track it for miles, eventually killing the animal due to its vulnerability brought on by exhaustion[11]). In 2008, researchers in Germany reported on the mechanisms that cause the runner's high. Using PET scans combined with recently available chemicals that reveal endorphins in the brain, they were able to compare runners’ brains before and after a run.[12] It is also suggested by many[who?] that endorphins are some of the many chemicals that contribute to runner's high; other candidates include epinephrine, serotonin, and dopamine. Previous research on the role of endorphins in producing runner's high questioned the mechanisms at work, their data possibly demonstrated that the “high” comes from completing a challenge rather than as a result of exertion.[13] Studies in the early 1980s cast doubt on the relationship between endorphins and the runner's high for several reasons:
  • The first was that when an antagonist (pharmacological agent that blocks the action for the substance under study) was infused (e.g., naloxone) or ingested (naltrexone) the same changes in mood state occurred as when the person exercised with no blocker.
  • A study in 2003 by the Georgia Institute of Technology found that runner's high might be caused by the release of another naturally produced chemical, anandamide.[14][15] The authors suggest that the body produces this chemical to deal with prolonged stress and pain from strenuous exercise, similar to the original theory involving endorphins. However, the release of anandamide was not reported with the cognitive effects of the runner's high; this suggests that anandamide release may not be significantly related to runner's high.[15]
  • A study at the University of Arizona, published in April 2012, argues implicitly that endocannabinoids are, most likely, the causative agent in runner's high, while also arguing this to be a result of the evolutionary advantage endocannabinoids provide to endurance-based cursorial species. This largely refers to quadruped mammals, but also to biped hominids, such as humans. The study shows that both humans and dogs show significantly increased endocannabinoid signaling following high intensity running, but not low-intensity walking. The study does not, however, ever address the potential contribution of endorphins to runner's high.[16] However, in other research that has focused on the blood–brain barrier, it has been shown that endorphin molecules are too large to pass freely, thus very unlikely to be the cause of the runner's high feeling of euphoria.[17]

Depersonalization disorder

Endorphins are known to play a role in depersonalization disorder. The opioid antagonists naloxone and naltrexone have both been proven to be successful in treating depersonalization.[18][19] To quote a 2001 naloxone study, “In three of 14 patients, depersonalization symptoms disappeared entirely and seven 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.”


In 2003, clinical researchers reported that profound relaxation in a float tank triggers the production of endorphins.[20] This explains the pain relief experienced during float sessions.[21]


In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins.[22][23] In another study, higher levels of endorphins were found in cerebrospinal fluid after patients underwent acupuncture.[24] In addition, naloxone appeared to block acupuncture’s pain-relieving effects.


A placental tissue of fetal origin — i.e., the syncytiotrophoblast — excretes beta-endorphins into the maternal blood system from the 3rd month of pregnancy. A recent study[25] proposes an adaptive background for this phenomenon. The authors argue that fetuses make their mothers endorphin-dependent then manipulate them to increase nutrient allocation to the placenta. Their hypothesis predicts that: (1) anatomic position of endorphin production should mirror its presumed role in foetal-maternal conflict; (2) endorphin levels should co-vary positively with nutrient carrying capacity of maternal blood system; (3) postpartum psychological symptoms (such as postpartum blues, depression, and psychosis) in humans are side-effects of this mechanism that can be interpreted as endorphin-deprivation symptoms; (4) shortly after parturition, placentophagy could play an adaptive role in decreasing the negative side-effects of foetal manipulation; (5) later, breast-feeding-induced endorphin excretion of the maternal pituitary saves the mother from further deprivation symptoms. These predictions appear to be supported by empirical data.[25]


From the Greek: word endo ενδο meaning “within” (endogenous, Greek: ενδογενής, “proceeding from within”) and morphine, from Morpheus, Greek: Μορφέας, the god of sleep in the Greek mythology, thus ‘endo(genous) (mo)rphine’.


  1. ^ Oswald Steward: Functional neuroscience (2000), page 116. Preview at: Google books.
  2. ^ a b “The Reality of the “Runner's High””. UPMC Sports Medicine. University of Pittsburgh Schools of the Health Sciences. http://sarahcannonresearch.co.uk/your-health/index.dot?id=13764&lang=English&db=hlt&ebscoType=healthindex&widgetTitle=EBSCO%20Health%20Library%20Index. Retrieved 2008-10-15.
  3. ^ “‘Sexercise' yourself into shape”. Health. BBC News. 2006-02-11. http://news.bbc.co.uk/2/hi/4703166.stm. Retrieved 2008-10-15.
  4. ^ “Get more than zeds in bed -“. Mind & body magazine – NHS Direct. UK National Health Service. Archived from the original on 2008-06-18. http://web.archive.org/web/20080618193933/http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=2504. Retrieved 2008-10-15.
  5. ^ a b 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.
  6. ^ “Role of endorphins discovered”. PBS Online: A Science Odyssey: People and Discoveries. Public Broadcasting System. 1998-01-01. http://www.pbs.org/wgbh/aso/databank/entries/dh75en.html. Retrieved 2008-10-15.
  7. ^ Hughes J, Smith T, Kosterlitz H, Fothergill L, Morgan B, Morris H (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.
  8. ^ Simantov R, Snyder S (1976). “Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor”. Proc Natl Acad Sci USA 73 (7): 2515–9. doi:10.1073/pnas.73.7.2515. PMC 430630. PMID 1065904. http:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC430630/.
  9. ^ 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 521124. PMID 15383669. http:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC521124/.
  10. ^ Kream RM, Stefano GB (October 2006). “De novo biosynthesis of morphine in animal cells: an evidence-based model”. Medical science monitor : international medical journal of experimental and clinical research 12 (10): RA207–19. PMID 17006413. http://www.medscimonit.com/fulltxt.php?ICID=459203.
  11. ^ http://www.youtube.com/watch?v=826HMLoiE_o
  12. ^ Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR (February 2008). “The Runner's High: Opioidergic Mechanisms in the Human Brain”. Cerebral cortex (New York, N.Y. : 1991) 18 (11): 2523–31. doi:10.1093/cercor/bhn013. PMID 18296435.
  13. ^ Hinton E, Taylor S (1986). “Does placebo response mediate runner's high?”. Percept Mot Skills 62 (3): 789–90. PMID 3725516.
  14. ^ “Study links marijuana buzz to ‘runner's high'”. CNN.com. 2004-01-11. http://edition.cnn.com/2004/HEALTH/01/11/marijuana.exercise.reut/. Retrieved 2008-10-15.
  15. ^ a b Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A (December 2003). “Exercise activates the endocannabinoid system”. NeuroReport 14 (17): 2209–11. doi:10.1097/01.wnr.0000097048.56589.47. PMID 14625449.
  16. ^ Raichlen, David A.; et al. (April 15, 2012). “Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’”. Journal of Experimental Biology (215): 1331–1336. doi:10.1242/jeb.063677. http://jeb.biologists.org/content/215/8/1331.abstract.
  17. ^ Burfoot, Amby (June 1, 2004). “Runner’s high”. Runner's World. http://www.runnersworld.com/article/0,7120,s6-243-297–1102-0,00.html.
  18. ^ Nuller YL, Morozova MG, Kushnir ON, Hamper N (June 2001). “Effect of naloxone therapy on depersonalization: a pilot study”. J. Psychopharmacol. (Oxford) 15 (2): 93–5. doi:10.1177/026988110101500205. PMID 11448093. http://jop.sagepub.com/cgi/pmidlookup?view=long&pmid=11448093.
  19. ^ Simeon, Daphne. “An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder”. Journal of Clinical Psychopharmacology. http://journals.lww.com/psychopharmacology/Abstract/2005/06000/An_Open_Trial_of_Naltrexone_in_the_Treatment_of.13.aspx. Retrieved 2011-10-13.
  20. ^ Anette Kjellgren, 2003, The experience of floatation REST (restricted Environmental stimulation technique), subjective stress and pain, Goteborg University Sweden,
  21. ^ Kjellgren A, Sundequist U et al.. “Effects of flotation-REST on muscle tension pain”. Pain Research and Management 6 (4): 181–9.
  22. ^ Johnson C (1999-06-04). “Acupuncture works on endorphins”. News in Science, ABC Science Online. Australian Broadcasting Corporation. . Retrieved 2008-10-15.
  23. ^ Napadow V, Ahn A, Longhurst J, Lao L, Stener-Victorin E, Harris R, Langevin HM (September 2008). “The status and future of acupuncture clinical research”. Journal of alternative and complementary medicine 14 (7): 861–9. doi:10.1089/acm.2008.SAR-3. PMID 18803495.
  24. ^ Clement-Jones V, McLoughlin L, Tomlin S, Besser G, Rees L, Wen H (1980). “Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain”. Lancet 2 (8201): 946–9. doi:10.1016/S0140-6736(80)92106-6. PMID 6107591.
  25. ^ a b Apari P, Rózsa L (2006). “Deal in the womb: fetal opiates, parent-offspring conflict, and the future of midwifery”. Medical Hypotheses 67 (5): 1189–1194. doi:10.1016/j.mehy.2006.03.053. PMID 16893611. http://www.zoologia.hu/list/apari_rozsa.pdf.

External links

This article uses material from the Wikipedia article Endorphins, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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    In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins.[22][23] In another study, higher levels of endorphins were found in cerebrospinal fluid after patients underwent acupuncture.[24] In addition, naloxone appeared to block acupuncture’s pain-relieving effects.

  5. Several researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins.[22][23] In another study, higher levels of endorphins were found in body!

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