This article reviews studies evaluating the relationship between endorphins and major depressive disorder. Individuals with depression were found to have lower levels of beta-endorphins. The results were limited by methodological differences. Alternatives to antidepressants that potentially increased beta-endorphin levels were examined. This included exercise, acupuncture and electroconvulsive therapy. Each of these modalities has been shown to increase beta-endorphin levels although the results were inconclusive. Further research is needed to better define the relationship between these modalities and endorphin levels. Introduction Animal and human research studies illustrate the contribution of central opioid systems in major depressive disorder (MDD). The most common endogenous opioid has been found to be beta-endorphin (Hegadoren, 2009). Low levels of plasma beta-endorphin lead to depressive symptoms. Many individuals with major depressive disorder do not fully respond to traditional antidepressant medications. Effective alternatives to medications, including exercise, electroconvulsive therapy, and acupuncture, help relieve depressive symptoms by increasing plasma levels of beta-endorphins. Background Opioid neuropeptides were first discovered in 1974 by two individual groups of researchers. John Hughes and Hans Kosterlitz were studying the brain of a pig and found a small amino acid molecule, enkephalin (Hughes, 1975). Shortly thereafter, Rabi Simantov and Solomon Snyder discovered endporphins in the calf brain, short for endogenous morphine. Beta-endorphin is a 31 amino acid C-terminal fragment molecule that is produced in the pituitary gland and arcuate nucleus of the hypothalamus. It is found throughout the body, including... middle of paper ......service utilization and social morbidity associated with depressive symptoms in the community. JAMA 1992; 267 (11): 1478-83 Li, CH Proc Natl. It happens. Sci. Public Health Reports (Interagency Team at NIMH and NIDA Studies on How Acupuncture Works.) (1974-), vol. 95, no. 5 (September - October 1980), pp. 503-504Wilson, Ronald W. and Elmassian Bonnie J., The American Journal of Nursing, vol. 81, no. 4 (April 1981), pp. 722-725 Terman, M, Terman JS, Quitkin FM, et al. Light therapy for seasonal affective disorder: a review of effectiveness. Neuropsychopharmacology 1989; 2(1):1-2Unutzer J, Patrick DL, Simon G, et al. Depressive symptoms and cost of health services in HMO patients aged 65 years and older: a 4-year prospective study. JAMA 1997; 277 (20):1618-2Prince, Raymond, Ethos, vol. 10, no. 4, issue dedicated to shamans and endorphins (winter, 1982), pp. 303-316