Tuesday, 18.05.2021

Peter R. Martin: Historical Vocabulary of Addiction

 

Exercise

 

        According to the current electronic version of the Oxford English Dictionary (OED), the noun exercise is from the Middle English, derived from the Old French exercice and the Provençal exercici, exercise.  These originate from the Latin noun exercitium, transformed from the verb exercēre, which means “to keep at work, busy, employ, practise, train.”  The etymology of exercēre, according to OED, “is obscure… often regarded as having meant primarily ‘to drive forth (tillage beasts),’ and hence ‘to employ, set to work.’”  The verb exercēre is a combination of the Latin prefix ex- and the verb arcēre which means “to shut up, restrain.”  An example of the first use of exercise in the English language is from c1340 in the Psalter of Richard Rolle (circa 1300–1349), an English hermit, mystic and religious writer, also known as Richard Rolle of Hampole or de Hampole (Everett 1922): “I rase fra ded til lyf, fra ydelnes til excercise in godis seruys.”  The definition of exercise in this quotation is: “The action of employing in its appropriate activity (an organ, a faculty, or power), of giving practical effect to (a right), of exerting (influence or authority); the state or condition of being in active operation.”

        Of the many definitions of exercise, the one that seems most relevant to addiction is: “Exertion of the muscles, limbs, and bodily powers, regarded with reference to its effect on the subject; especially such exertion undertaken with a view to the maintenance or improvement of health.”  This sense of the word was first used c1386 in Nun's Priest's Tale a part of Canterbury Tales by Geoffrey Chaucer, the English poet and author widely considered the greatest English poet of the Middle Ages (Chaucer 2013): “Attempre dyete was al hir phisik, And exercise and hertes suffisaunce.”  Later quotations support the role of exercise in health and a balanced life.  Francis Bacon (1561–1626), the English philosopher and statesman who served as Attorney General and as Lord Chancellor of England and was highly influential in the scientific revolution, expressed in his Sylva sylvarum (Bacon and Rawley 1626): “Use not Exercise and a Spare Diet..if much Exercise, then a Plentifull Diet.”  This quote accurately expresses the fundamental principle of nutrition, specifically, calories must be consumed via food to sustain exercise.  John Dryden (1631–1700), the English poet, literary critic, translator and playwright who was appointed England's first Poet Laureate in 1668 and dominated the literary life of Restoration England, wrote in his Fables Ancient and Modern (Dryden 1774): “The Wise, for Cure, on Exercise depend.”   Dryden herein referred to the role of exercise in prevention and healing of disease.  Samuel Johnson (1709–1784), an English writer who made lasting contributions to English literature as a poet, playwright, essayist, moralist, literary critic, biographer, editor and lexicographer in 1779, wrote in The letters of Samuel Johnson (1992): “Exercise is labour used only while it produces pleasure.”  Johnson’s quotation points to a paradoxical aspect of exercise – even though it can cause the physical exhaustion of labor, nevertheless, it may be rewarding to some.  

        Exercise has been considered desirable throughout history, as physical exertion, despite exhaustion, can lead to a balanced and healthy life and can also provide joy.  Hence, physicians deemed it appropriate to prescribe exercise for various medical indications.  Sir Arthur Brooke Faulkner (1769–1845), an English physician who served with the army in Spain, Holland, Sicily and Malta and was knighted in 1815 for his service, recommended exercise for dyspepsia and attributed the beneficial effects to effects on the integument of the body (1806): 

        “…I have been enabled, by experiments repeatedly and cautiously instituted, to ascertain that a few minutes only of exercise, conducted so as to induce perspiration, have enabled a dyspeptic person to digest a quantity of food which a whole day of his accustomed sluggish exercise was inefficient for.  It was necessary, however, to employ the exercise just before eating.  I hold it, therefore, as a circumstance of indispensable consequence in the treatment of dyspepsia that exercise be employed to the extent of promoting a free and copious perspiration; and I conceive that the less violent the exertions are for this purpose, the effects will be the more happy and permanent.  It should be an object of the first consequence, in the treatment of this disease, to derive to the skin in these cases where dryness of the cuticle opposes this derivation.  In such cases, those means which have been termed indirect are the only ones upon which any perfect confidence can be placed. The exhibition of medicines, and the regulations of diet, in such cases, ought to be regarded only as auxiliary and co-operative.

        “It has long been observed, that there subsists a very remarkable sympathy between the stomach and surface of the body.  There is scarcely an aphorism in medicine more hackneyed.  It seems, therefore, extraordinary that it should not be more attended to in the treatment of the disease I have been considering.  Since it is our great object to effect a change in the functions of depraved digestion, when the cure of dyspepsia is undertaken, one obvious method of effecting this, according to the principle I have alluded to, is to produce a change in the surface.  But this does not seem to be accomplished by exercise, except by inducing its perspiring condition.”

        To truly appreciate the wisdom of Faulkner’s recommendation, it should be emphasized that, in his time, dyspepsia signified a great many disorders, a number of which are now viewed as having significant psychiatric underpinnings.  Moreover, many conditions that result in dyspepsia, in common parlance termed indigestion, are actually due to overindulgance in food and drink, evocative of what today are considered addictive disorders.  Robert Kinglake (1765–1842), an English physician known as a medical writer, emphasized the broad clinical swath of this diagnosis and that such conditions are particularly difficult to treat (1802):

        “The experienced medical practitioner will admit that a large majority of chronic diseases, and not a small proportion of those of an acute description, owe their origin to indigestion; nor will it be denied by the most intelligent of the profession, that the difficulties in the way of restoring the stomach to a due performance of its digestive function, are such as often to baffle the most approved modes of treatment.”

        These early 19th century quotations describe the beneficial effect of regular, perspiration-inducing exercise in medical management of a range of chronic conditions, understood as dyspepsia, but also including mental disorders and over-indulgence in food and drink.    

        Very much research was needed before the intuitive prescription of exercise for the very wide range of disorders implied by “dyspepsia” could be scientifically supported.  Exercise was reported to activate the cardiopulmonary system along with intense muscle contractions (Smith 1859).  That substantial energy expenditures occurred without detectable increase of body temperature was first recognized by the English physician known for his invention of the clinical thermometer, Sir Thomas Clifford Allbutt (1836–1925), upon carefully monitoring his own body temperature during a strenous ascent of Mont Blanc.  The lack of a significant elevation of body temperature despite energy combustion from exercise, has been shown to be due to hypothalamic activation of heat dissipation mechanisms, among them perspiration, to maintain body temperature in the optimal range (Lomax and Schönbaum 1979).  That combustion of foodstuffs are required for muscular contractions and elements of the body are catabolized in the process was suggested by the 1877 report of increased urinary nitrogen output by Austin Flint II (1836–1915), an American physician who carried out extensive experimental investigations in human physiology, including establishing the glycogenic function of the liver.  If exercise is sufficiently strenuous, it activates the sympathetic-adrenal system, much as the physiological response to threat, termed in 1920 as “fight or flight” by Walter Cannon (1871–1945), a leading American physiologist of the first part of the 20th century.  Controlled and limited episodes as occur during exercise do not activate the pathological stress response, initially described in 1937 by Hans Selye (1907–1982), the pioneering Hungarian-Canadian endocrinologist.  Rather, exercise triggers a complex molecular series of changes in acute inflammatory markers (e.g., interleukin-6) and metabolic pathways (e.g., glycolysis and fatty acid oxidation) and remains a pillar of cardiovascular, immune and cognitive health (Contrepois, Wu, Moneghetti et al. 2020).

        Exercise has, accordingly, been prescribed for the treatment of obesity with the goal of increased catabolism over food intake (Chlouverakis 1975).  Pharmacologic strategies to reduce appetite, predominantly involving stimulants, have been implemented to circumvent exercise and diet changes necessary for weight reduction.  However, use of stimulants have significant abuse liability and addiction potential (Craddock 1976) and such anorexigens have shown no significant advantages over behavioral approaches which include exercise (Öst and Götestam 1976).  Obesity has become an ever-mounting clinical challenge in recent decades.  Large proportions of the population are affected (Ogden, Carroll, Curtin et al. 2006) and obesity-associated comorbidities reduce the life expectancy of severely obese persons by an estimated 5–20 years (Fontaine, Redden, Wang et al. 2003), mirroring another devastating disorder in which lifestyle interventions were the predominant treatment strategy – addiction.  Clinical descriptions of over-eating in obesity share many of the characteristics of addictive disorders (Martin, Weinberg and Bealer 2007) and the neurobiology of brain reward circuitry that are activated by drugs of abuse overlay those that mediate food motivated behaviors (Volkow and Wise 2005). 

        The paradigm shift of viewing obesity as over-eating and its conceptualization as a behavioral addiction (Holden 2001), opened the door to treatment of drug use disorders with exercise interventions.   Accumulating research has demonstrated that exercise is a potentially useful adjunct to treatment of drug or behavioral addiction.  Aerobic exercise produces a host of positive psychological effects, including increased self-esteem and well-being, enhanced mood and stress reduction (Norris, Carroll and Cochrane 1990).  Human and animal studies have reported that exercise produces interoceptive changes that can resemble those produced by addictive drugs, including subjective ratings of joy, pleasure and euphoria that are attributable to activation of the endogenous opioid system (Janal, Colt, Clark and Glusman 1984) as well as increased central dopamine concentrations (Heyes, Garnett and Coates 1988).  Given that many addictive drugs produce their reinforcing effects by increasing dopamine neurotransmission in mesolimbic and mesocortical pathways, chronic exercise may produce functional changes in these pathways, leaving an organism less susceptible to drug reward (Goeders and Smith 1983). 

        Chronic exposure to drugs of abuse as occurs in addiction causes specific regions of the brain to become responsive to drug cues, especially when a person is attempting to discontinue addictive drug use  (Martin 2020).  For example, during nicotine abstinence, the presence of cigarette images has been shown by functional magnetic resonance (fMRI) to increase activation in both the mesolimbic (nucleus accumbens, amygdala and hippocampus) and the mesocortical (prefrontal cortex, orbitofrontal cortex (OFC) and anterior cingulate) dopamine circuits, in anticipation of both the reinforcing effects and the incentive salience of the drug (Due, Huettel, Hall and Rubin 2002).  Specifically, the value of the drug and drug-related stimuli is enhanced at the expense of other reinforcers in the environment.  The changes in brain dopamine function are likely to result in decreased sensitivity to natural reinforcers since dopamine also mediates the reinforcing effects of natural reinforcers and on disruption of frontal cortical functions, such as inhibitory control and salience attribution (Volkow, Fowler and Wang 2003).  It seems reasonable that exercise, due to its own rewarding effects, can serve to compete with salience of drugs of abuse.

        The most compelling evidence that exercise could refocus brain activation and reduce drug cravings has come from research on nicotine addiction (Ussher, Taylor and Faulkner 2008).  When cigarettes are withheld, smokers show increased activation of the OFC when presented with cigarette-related cues, along with increased cravings.  Following exercise and exposure to the same cues, the previously activated areas of the frontal cortex become less activated. This suggests that following exercise, individuals find cigarette stimuli less salient and demonstrate less cravings and activation of OFC, supported by behavioral data that exercise reduces subjective desire to smoke and that cue-elicited cravings are attenuated. Taken together, these results demonstrate that exercise can reduce the motivational drive (via OFC activation) towards smoking even in the presence of smoking stimuli although other neurobiolobical mechanisms may be relevant, such as stress reduction, altered mood and enhanced well-being and motivation for health.  An exercise intervention was also associated with diminished salience and craving for cannabis cues and reduced use in individuals who previously experessed no intention to stop using cannabis (Buchowski, Meade, Charboneau et al. 2011; Charboneau, Dietrich, Park et al. 2013).  Additionally, benefits of exercise programs may extend to neuropsychiatric benefits and cognitive outcomes for subjects with co-occurring psychiatric diagnoses and drug use disorders (Ashdown-Franks, Firth, Carney et al. 2020)

        Epidemiological studies report that participation in activities that promote physical fitness is associated with a lower incidence of tobacco and substance use among adolescents (Field, Diego and Sanders 2001).  These findings support the use of exercise in both prevention and treatment of addiction.  Interestingly, over-eating has become the major cause of steatohepatitis, a disorder that was in the past a signal of alcohol use disorder (James and Day 1999), and exercise is a cornerstone of its treatment  (Linden, Sheldon, Meers et al. 2016).  Additionally, bariatric surgery, the most efficient means of treating severe obesity has been found to have a post-surgical risk of development of new-onset alcoholism, possibly “trading” addictions (Hsu, Benotti, Dwyer et al. 1998; Hagedorn, Encarnacion, Brat and Morton 2007).  The multiple inverse relationships between exercise and behavioral/alcohol/drug addictions suggest a potential evolutionary role of physical activity in maintenance of physical and emotional health that has been dislocated by our affluent society.  More important, these observations point to the importance of exercise to help recreate the level of activity that is required to maintain health and vitality (Warburton, Nicol and Bredin 2006) we appear to have lost in the “developed” world. 

 

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January 7, 2021