Monday, 17.05.2021

Peter R. Martin: Historical Vocabulary of Addiction




       According to the current electronic version of OED, the noun nicotine was formed within English by derivation from the nouns nicotian and nicotiana and the suffix -in.  The noun nicotian, now only rarely used, is a borrowing from French nicotiane defined in OED as: “The tobacco plant, Nicotiana tabacum; any plant of the genus Nicotiana. Also: tobacco.”  Of note, the tobacco plant is named after Jean Nicot de Villemain (1530–1600), French ambassador in Lisbon (1558–60) and lexicographer, who introduced tobacco into France in 1560.  Some, at that time, proposed smoking for health, possibly protection from the plague.  The name Nicot was thus combined with the suffix -ian, meaning “of or belonging to,” representing a Latin suffix -iānus, i.e., an original or connecting vowel -i-, with suffix -ānus.  The noun nicotiana is a borrowing from Latin, a version of which has spread to Italian and Spanish, which is employed to designate the genus and related species of tobacco.  The noun nicotine is defined in OED as: “A toxic, colourless or yellowish, oily liquid alkaloid which is the chief active constituent of tobacco, acting as a stimulant in small doses, but in larger amounts blocking the actions of autonomic nerve and skeletal muscle cells; 3-(1-methyl-2-pyrrolidinyl)pyridine, C10H14N2.”  

       The noun nicotian was the first used in the English language in the translation of The Three Books (Monardes 1577): “This Hearbe is called Nicotiane, of the name of hym that gaue the firste intelligence thereof into this Realme.”  An example of the first use of the noun nicotiana in English appears in Maison Rustique; or, The Countrie Farme translated by Richard Surflet (c. 1560–1606), a British physician, surgeon and translator (Estienne, Liebault and Surflet 1600): “This herbe is called Nicotiana of the name of an ambassadour which brought the first knowledge of it into this realme.”  It was not until much later that the noun nicotine was first used in technical English.  An example is found in the text of A System of Chemistry (1817), written by the Scottish chemist and mineralogist, Thomas Thomson (1773–1852), whose writings contributed to the early spread of Dalton's atomic theory: “Of nicotin. This substance exists in the leaves of the nicotiana latifolia, or tobacco, and gives that plant its peculiar properties.”  The noun is also found in literature as in the novel Of Human Bondage by William Somerset Maugham (1874–1965), an English playwright and novelist, who qualified as a physican but gave up medicine due to his literary success (1915): “She had long, beautiful hands, with fingers deeply stained by nicotine.” 

       The importance of nicotine with respect to addiction is that it is the major psychoactive substituent in tobacco.  The noun tobacco is altered from Spanish tabaco, according to OED, “the name in the Carib of Haiti of the Y-shaped tube or pipe through which the Indians inhaled the smoke; but [others claim it is] applied to a roll of dried leaves which was kindled at the end and used by the Indians like a rude cigar… the name had been taken by the Spaniards as that of the herb or its leaf, in which sense it passed from Spanish into the other European languages…The original forms tabacotabacco, were retained in English to the 18th century, but gradually driven out by tobacco.” 

       The OED definition of the noun tobacco is: “The leaves of the tobacco-plant (Any one of various species of Nicotiana (N.O. [natural order of plants] Solanaceæ), especially N. Tabacum, a native of tropical America…) dried and variously prepared, forming a narcotic and sedative substance widely used for smoking, also for chewing, or in the form of snuff and to a slight extent in medicine.”  An example of its first use in the English language is in The Description of England by William Harrison (1535–1593), an English historian and topographer (1877): “In these daies [1573] the taking-in of the smoke of the Indian herbe called Tabaco, by an instrument formed like a litle ladell, wherby it passeth from the mouth into the hed & stomach, is gretlie taken-vp & vsed in England.” The noun snuff is probably derived, according to OED, from “Dutch and Flemish snuf or snuif (West Frisian snuf ) in the same sense, apparently an abbreviation of snuiftabak” and is defined as: “A preparation of powdered tobacco for inhaling through the nostrils (in the southern United States, usually taken orally).” An example of its first use in English is from the The London Gazette (Anonymous 1683): “James Norcock, Snuffmaker and Perfumer, ...sells all sorts of Snuffs, Spanish and Italian.”

       The uncertain role of tobacco in the medicine of the day is described in an editorial entitled “Remarks on the History and Use of Tobacco(Medicus 1810):

       “The powers and the properties of the vegetable narcotics, either to destroy or to save, have been enough distinguished, to make those who wish for the improvement of medical science, lament that our knowledge of them is still so indeterminate, that it may be said to approximate to ignorance. Some of the properties of some of these substances, may have been tolerably explained; but of others, so little is ascertained, that they still remain, as to their influence upon the animal functions, in a state of great obscurity…

       “It has been the fate of the NICOTIANA TABACUM to have credulous and hyperbolical friends; enemies prejudiced, malignant, and unjust.  With the one party it was the great Panacea (Everard 1587), the curer of every evil, the soother of every care. –With the other, it was a debaser of the human mind, enervated the body, and was fit only to be used by diabolical spirits in Pandaemonium.  Both its friends and enemies were found in every rank of society, from the King to the peasant.  Poets, priests, physicians, and moralists, were, by turns, its panegyrists and its defamers.

       “A writer of the period when Tobacco was at the acme of its influence, has brought together, into one paragraph, all its virtues and its vices, in a manner peculiar to himself. "Tobacco, divine, rare, superexcelient Tobacco, which goes far beyond all their panaceas, potable gold, and philosophers stones, a sovereign remedy to all diseases. A good vomit, I confesse, a virtuous herb, if it be well qualified, opportunely taken, and medicinally used; but, as it is commonly abused by most men, which take it as tinkers do ale, it is a plague, a mischief, a violent purger of goods, lands, health; hellish, devilish and damned Tobacco, the ruine and overthrowe of body and soul."  With this curious summary of honest Burtons, I must conclude these miscellaneous Remarks on a Plant, whose dominion over mankind has been, for a period, most extensive.”

       Based on this quotation, the notion of abuse/addiction in much the same vein as occurs with alcohol (“as tinkers do ale”) seems to have been accepted for at least two centuries.  While tobacco was considered to play a role in medicine at one point, recognition of diverse toxicities began to accumulate as discussed in the editorial, “Pathogeneses of Tobacco and Nicotine.—Neuroses Produced by Tobacco” (Anonymous 1873).  Eventually, the negatives associated with tobacco outweighed the positives.  Horatio Curtis Wood, Jr. (1841–1920), an American physician and biologist, stated in his influential text A Treatise on Therapeutics: Comprising Materia Medica and Toxicology (1874): “Tobacco ...has almost passed out of sight as a therapeutic agent.”

       The major psychoactive agent of tobacco continued to be of tremendous scientific interest.  Nicotine was originally isolated from the tobacco plant (Posselt and Reimann 1828) by two German scientists, a physician Wilhelm Heinrich Posselt (1806–1877) and a chemist Karl Ludwig Reimann (1804–1872); the empirical chemical formula was described (1843) by a Belgian physicist and chemist, Louis-Henri-Frédéric Melsens (1814–1886); the structure of nicotine was discovered (1893) by a German chemist, Adolf Pinner  (1842–1909); and nicotine was first synthesized (Pictet and Rotschy 1904) by a Swiss chemist, Amé Pictet (1857–1937).  

       The early era of studies on the pharmacology of nicotine and its role in cholinergic neurotransmission (Dixon and Hoyle 1929) are summarized in a lecture (1935) delivered to the Royal Society of Medicine entitled “Pharmacology of Nerve Endings” by Sir Henry Dale (1875–1968).  Dale was an eminent English pharmacologist and physiologist who, for his study of acetylcholine as agent in chemical neurotransmission, shared the 1936 Nobel Prize in Physiology or Medicine. 

       Over the years, it was demonstrated that nicotine acts as a receptor agonist at nicotinic acetylcholine receptors (NAChRs) that are linked to ion channels and are found predominantly in the central and peripheral nervous system and muscle.  Most important with respect to addiction, the mechanisms of action of nicotine in the central nervous system are very similar to the stimulant amphetamine which has high proclivity for self-administration and abuse liability (Izquierdo and Izquierdo 1971):

       “Both these drugs have several well known central effects in common: (a) cortical and hippocampal EEG alerting; (b) increased performance and retention of conditioned responses; (c) central catecholamine depletion or increased turnover; (d) increased hippocampal RNA concentration, probably secondary to the EEG effect.  Effects (a), (b), and (c) are shared, in general, by a number of amphetamine analogs... Amphetamine and nicotine increase self-stimulation rates.  The former is less effective when electrodes are in the posterior hypothalamus than when they are in the septum, anteromedial hypothalamus, or midbrain tegmentum.”

       Nicotine facilitates acquisition of a variety of learned tasks due to central not peripheral actions of the drug and these facilititating effects of nicotine on learning are based on adrenergic mechanisms (McGaugh 1973).  Additionally, nicotine acts on reward circuits of the brain by activating NAChRs in the ventral tegmental area to cause dopamine release in neurons that project to the nucleus accumbens which may contribute to nicotine use disorder and also the high prevalence of co-occurrence of other alcohol/drug use disorders with smoking cigarettes (Hyman, Malenka and Nestler 2006).  Finally, nicotine affects the set point around which body weight is regulated and nicotine suppresses hunger and cessation of smoking increases appetite and caloric intake (Perkins 1992; Romero, Daniels, Gipson and Sanabria 2018).

       It was reasoned that the percentage of nicotine in various kinds of tobacco was probably relevant to smoking behavior if nicotine was the key ingredient in tobacco (Anonymous 1909):

       “[I]t would appear to be true as a general proposition that the more nicotine there is in a cigar or any other form in which tobacco is smoked, the more the smoker is likely to take into the system. It is, therefore, of some importance to know the relative amounts of nicotine contained in different kinds of tobaccos. Further, if the results of such an inquiry show that the percentage of nicotine rises and falls pari passu with the character of the tobacco as ‘strong’ or ‘mild’ when judged by a smoker, collateral evidence will be afforded of the correctness of the view that the effects of smoking are principally due to the nicotine.”  

       Of note, there are those who have proposed that nicotine content is not as important for all with the “cigarette habit” (Finnegan, Larson and Haag 1945).  However, nicotine content can now be regulated by industrial processes (Connolly, Alpert, Wayne and Koh  2007), thus complicating estimates of the level of use in the population and simultaneously estimating nicotine use disorder based only on cigarettes smoked. 

       Tobacco use can result in nicotine use disorder which, in turn, is frequently associated with co-occurring alcohol and drug use disorders as well as mood, anxiety and personality disorders (Grant, Hasin, Chou et al. 2004; Martin, Weinberg and Bealer 2007).  Tobacco use also has enormous healthcare costs in the United States, recently estimated at almost $200 billion per year (Ekpu and Brown 2015).  Tobacco use is the leading cause of preventable morbidity and mortality among adults worldwide, e.g.,  tobacco use is associate with 1 in 5 deaths per year in the United States (United States Surgeon General 2014).  The major health consequences associated with tobacco use, substantively due to pyrolysis products formed on smoking of tobacco products, include coronary heart disease; stroke; chronic obstructive pulmonary disease; lung and other cancers; and increased risk of pre-term delivery and low birth weight, among many other conditions.  Despite the availability of many delivery platforms, like cigars, snuff, or dipping/chewing tobacco, the major instrument for self-administering nicotine remains cigarette smoking.  An electronic form of nicotine delivery, called “vaping” in the vernacular, was initially considered safer than cigarettes.  Accordingly, vaping began to be used for smoking cessation and its prevalence rapidly increased, especially in the young who often initiated nicotine use with vaping instead of cigarettes.  Now it promises to have its own set of even more severe medical complications (Lerner, Sundar, Yao et al. 2015; Palazzolo 2013). 

       The most recently available rates of smoking reflect the distinction between nicotine use as typically quantified (numbers of cigarettes, cigars, snuffing, etc.) and whether a consumer actually meets diagnostic  criteria (DSM-IV) for nicotine use disorder (Fagerström 1978; Grant, Shmulewitz and Compton  2020).  Representative U.S. data on 12-month prevalences of nicotine use, nicotine dependence and nicotine dependence among users were determined during the periods 2001-2002 and 2012-2013.  Recent declines in nicotine use were found, presumably due to population-level public health interventions.  However, there were significant increases in prevalence of severely dependent users during this time-frame.  These are the individuals who are less likely to quit, require the majority of healthcare expenditures and may need other than currently available public health prevention efforts (e.g., increased price, elimination of advertising, protections against secondhand smoke) that have demonstrated benefical effects in less severe users.  Instead, these severely dependent individuals may profit from evidence-based addiction treatment interventions based on a pharmacopsychosocial model (Martin, Weinberg and Bealer 2007; Fisher, Pauly, Froeliger and Turner 2020).

       As the health consequences of smoking cigarettes became recognized (Larson, Haag and Silvette 1968), scientific interest arose concerning the differences between those who do and those who do not smoke (Heath 1958).  Initially, the focus was on descriptive features that may serve as risk factors for developing nicotine use disorder, such as taste perception (Krut, Perrin and Bronte-Stewart 1961), among others.  In subsequent decades, research expanded to include genetic and neurobiologic characteristics of those at particular risk for nicotine use disorder and its complications.  In particular, focus has been on co-occurring psychiatric disorders, especially depression (Moriguchi, Inagaki, Yi et al. 2020) and severe mental disorders (Wei, Wang, Wei et al. 2020) that are demonstrated to be significantly associated with nicotine use disorder (Bierut 2020).   The goal has been implementation of precision medicine approaches in treatment of nicotine use disorders employing antidepressants, nicotine replacement approaches and the partial agonist of α4β2NAChR, varenicline (Frank, Cinciripini, Deweese et al. 2020).  The ultimate goal in treatment of nicotine use disorders would be identification and reversal of plastic changes associated with learning and addiction (Jin, Tucker and Drenan 2020).



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February 4, 2021