Page 1 of 9 Impulse: The Premier Journal for Undergraduate Publications in the Neurosciences 2006 Endorphins, Exercise, and Addictions: A Review of Exercise Dependence Andrea Leuenberger1 1Lafayette College, Easton, PA 18042 Endorphins are endogenous opioids released from the pituitary gland that are believed to mediate analgesia, induce euphoria, and play a role in the reward system in the brain. It has been suggested that endorphins are responsible for creating the relaxed psychological state known as “runner’s high.” Studies examining the relationship between vigorous exercise and blood plasma endorphin levels have produced conflicting results. Some indicate a significant increase of endorphins during or after exercise while others do not. Inconsistent methods and experimental techniques have made it difficult to determine a relationship between exercise and endorphin elevations. Research has shown that opioidergic activity plays a role in addictions by mediating the development of reinforcing qualities of certain activities and substances. A newly- established condition known as exercise dependence defines exercise as an addiction, characterized by a compulsion to exercise excessively even when the consequences are harmful to an individual’s health, family relationships, and personal wealth (Griffiths, 1997; Hausenblas and Downs, 2002; Loumidis and Wells, 1998). Various surveys and questionnaires have been validated for determining the level of an individual’s dependence on and need for exercise. As researchers define a clear relationship between vigorous exercise and increased endorphin levels, causes of exercise dependence can be more concretely determined. Exercise dependence is not currently recognized by the DSM-IV, but its presence in certain human behaviors (similar to those of alcoholics and drug addicts) indicate that it should be precisely defined. Keywords: opioids; opioidergic activity; euphoria; runner’s high; genetics; reward system; compulsion Introduction Since their discovery in the mid-1970s, exercise induces an increase in endorphin the role of endorphins has been a widely studied release, procedural, definitional, and but enigmatic topic within the science of observational inconsistencies have prevented physiology. Although it has been three decades, consistently valid conclusions from being scientists are still searching for consistent drawn. The euphoric feelings generated by answers as to why the body produces endorphins endorphins, which may result from strenuous and how these peptides operate within the exercise, are believed to play a role in addiction. central nervous system. The name endorphin is While it is generally accepted that endorphins derived from two words, endogenous and induce euphoria, it is unclear whether exercise morphine, because these hormones act similar to causes an increase in endorphin levels. morphine (a natural opiate) within the natural Additionally, if exercise increases endorphin opioid system (McKim, 2003). Researchers levels, few studies have been performed to have found a correlation between vigorous measure whether this increase plays a role in exercise and elevated endorphin levels in blood exercise dependence. Individuals labeled as plasma (Goldfarb et al., 1987; Pierce et al., exercise-dependent show similar behaviors and 1993). While some evidence does suggest that Page 2 of 9 Endorphins, Exercise, and Addictions 2006 hormone levels to those with alcoholism and Opioid antagonists, including naloxone, drug addictions. naltrexone, and nalmefene, have all been shown Because findings of endorphin to block opioid receptors in both animal models elevations are so inconsistent, researchers and human studies (Dishman, 1985; Farrell, continually alter experimental strategies. 1985; O’Brien, 2004; Oswald and Wand, 2004). Unfortunately, this makes it difficult to Naloxone is the most commonly used opioid determine what, if any, strategies effectively antagonist in clinical studies as well as addiction measure endorphins and the physiological treatment (O’Brien, 2004). response to exercise. Based on the literature reviewed, it appears that endorphin activity may be highly variable from one individual to the Exercise May Increase Endorphin next, making this analysis even more complex Release (Goldfarb et al., 1987). Many researchers have not found significantly elevated endorphin levels Many studies have examined the after exercise, but many studies do, in fact, relationship between exercise and endorphin indicate a non-significant trend of this release, studying the role of these peptides in occurrence (Di Luigi et al, 2003; Goldfarb et al., exercise-induced euphoria as well as the 1998; Langenfeld et al., 1987). reduction of pain (Farrell, 1985; Goldfarb et al., 1987; Goldfarb et al., 1998 Langenfeld et al., 1987, Pierce et al., 1993). Endorphins are often Endorphins: Endogenous Opioids implicated in the euphoria known as “runner’s high,” the relaxed psychological state sometimes Endorphins are part of a general class of experienced during or after vigorous exercise hormones known as endogenous opioids, a such as running (Pierce et al., 1993). group which also includes enkephalins and Inconsistent evidence for a significant rise in dynorphins. The endorphin opioid consists of a endorphin release, however, makes it very specific 31-amino acid sequence, cleaved from a difficult to simply deduce that endorphins larger peptide known as proopiomelanocortin released due to exercise are the cause of (POMC) (Goldfarb et al., 1987; Harbach et al., euphoric feelings. In addition, Dishman (1985) 2000). Endorphins are released from the maintains that the so-called “runner’s high” has pituitary gland into the circulatory system. not been systematically nor thoroughly Neurons producing endorphins are located documented. mainly in the ventomedial arcuate nucleus, Similar to the euphoria data, results which projects to the hypothalamus and limbic from studies on pain reduction are also system (Oswald & Wand, 2004). Opioid conflicting due to inconsistent experimental peptides activate three different types of methods and results. In one study, subjects who receptors, mu (µ), kappa (_), and delta (_) ran 1.6 km at a self-selected pace took receptors, all of which act through a second significantly longer to report pain on their messenger (McKim, 2003; Zalewska-Kaszubska fingertip from a 1.2-kg weight. The analgesia, and Czarnecka, 2005). The affinity with which however, was reduced when a 2-mg dose of each opioid binds to the three different receptors naloxone was administered; a 10-mg dose of the can vary; endorphins primarily operate via the drug eliminated the analgesic effects altogether µ-opioid receptor (McKim, 2003). This receptor (Farrell, 1985). This indicates that the is known to mediate analgesic effects as well as endorphins released as a result of running could play a role in the reward system within the brain. be responsible for the reduced pain sensitivity. Evidence showing that endorphins can interfere However, this experiment has not been with the release of other neurotransmitters, replicated and follow-up studies have not including norepinephrine, dopamine, and examined this exact response. Non-replicated acetylcholine, have led to a belief that they work experiments, such as this one, and minimal data by modulating the presynaptic membranes of synapses other than their own (McKim, 2003). Page 3 of 9 Impulse: The Premier Journal for Undergraduate Publications in the Neurosciences 2006 make it difficult to confidently formulate a test, others late in the test, and some not at all. relationship between running and analgesia. While overall endorphin level increases did not Clinical research studies measuring prove significant during exercise and at varying endorphin levels before, during, and after intensities, investigators found a significant exercise are conflicting: some show significant elevation following the exercise period. increases where others do not. Additional However, the large amount of variability complications occur when researchers differ in between subjects may indicate different their definitions as to what constitutes acute, individual responses to different types of vigorous exercise. It still remains questionable exercise. as to what specific conditions, if any, induce While much data has been published endorphin release. It is possible that a specific about the relationship between endorphins and VO2max threshold must be met or maintained, a intensity of exercise, other researchers tested certain distance or length of time must be different forms of exercise – mostly the completed, or a specific form of exercise must difference between running and bicycling. be performed in order for the physiological Langenfeld et al. (1987) sought to determine response of endorphin release to occur. whether bicycling or running at 60% VO2max at a Farrell (1985) assessed the threshold by fixed time (1 hr) would significantly elevate looking at the effects of intensity and distance of endorphin levels and, if so, which form of running on endorphin-release in male subjects exercise was more effective. While a trend of by compiling results from multiple studies with increased endorphin levels was observed, varied time and distances of running. Analyses statistical analyses did not reveal significance. of these data indicated a trend of elevated One might question, however, if this is due to endorphin levels after exercise in all studies, the fact that an intensity