Tuesday, 18.05.2021

Peter R. Martin: Historical Vocabulary of Addiction




       According to the current electronic version of the Oxford English Dictionary (OED), the noun cocaine was formed within English by combination of the noun coca and the suffix -ine (“used unsystematically in forming names of extractive principles and chemical derivatives of various kinds”).  The noun coca from Spanish corresponds to cuca (Peruvian) and is defined in OED as: “The name in Bolivia of Erythroxylon coca, a shrub six or eight feet high; hence, applied to its dried leaves, which have been employed from time immemorial, with powdered lime, as a masticatory, appeaser of hunger, and stimulant of the nervous system.”  The definition of the noun cocaine is: “An important alkaloid obtained from the leaves and young twigs of the coca plant, valuable as a local anæsthesiant, and also used as a stimulant.”

       The noun coca was used in the English language before cocaine as exemplified (1616) in a book by John Bullokar (1574–1627), an English physician and lexicographer: “Coca, an hearbe of India, the leaues whereof being bruised and mixt with the powder of Cockles or Oysters in their shelles burnt the Indians [so-called because Christopher Columbus never clearly renounced his belief that he had reached the Far East and named the indigenous peoples he encountered “indios”] use in little balles to carry in their mouthes to preserue them from famine and great dryth.”

       For at least a thousand years, from the pre-Inca period, the Andean peoples of Peru, Bolivia, Ecuador, Colombia, northern Argentina and Chile chewed or brewed tea from the leaves of Erythroxylon coca, a plant that contains nutrients as well as the powerful stimulating alkaloid cocaine (Blejer-Prieto 1965).  There is archeological evidence of the remains of coca leaves in ancient Peruvian mummies and early pottery found in the region depicts humans with bulged cheeks, presumably chewing coca leaves (Gay, Inaba, Sheppard et al. 1975).  The coca plant was chewed by indigenous people to maintain their energy to work harder, longer, and with less food in brutally strenuous conditions at high altitudes as noted by Samuel Purchas (1577–1626), an English geographical editor and clergyman and Richard Hakluyt (1553–1616) a writer active in colonization of the New World (Purchas and Hakluyt 1625): “An herbe... Coca, which they carrie continually in their mouthes.”  The Spanish initially ignored native claims that the coca leaf gave them strength and energy, and forbade its use for religious reasons.  After discovering the great demand for coca, the Spaniards taxed the value of these crops.  In addition, the coca leaf was used among the indigenous Andean people for various medicinal purposes such as reducing inflammation and treatment of infections.  There is also evidence that a mixture of coca leaves and saliva were used as an anesthetic for trephanation. 

       The properties and unusual effects of the coca leaf became known in Europe with Spanish exploration of the New World (Mortimer 1901).  Amerigo Vespucci (1454–1512),  a Florentine merchant, explorer, and navigator after whom the New World was named, is said to have been the first European to discover the coca plant (Vespucci and Medici 1503).  The first European publication on coca was by Nicolás Monardes (1493–1588), a Seville physician and botanist who described the aboriginal practice of chewing a mixture of tobacco and coca leaves to induce: “great contentment…When they wished to make themselves drunk and out of judgment they chewed a mixture of tobacco and coca leaves which make them go as they were out of their wittes (Monardes 1569).”  In 1753, Joseph de Jussieu (1704–1779), a French botanist and explorer, was the first to classify the coca plant according to its botanical name Erythroxylon coca (Blejer-Prieto 1965).

       The cocaine alkaloid was first isolated from the plant by the German chemist Friedrich Gaedcke (1828–1890), who named it “erythroxyline” (Gaedcke 1855).  The German chemist Albert Niemann (1834–1861) isolated and called the alkaloid “cocaine,” derived from “coca” (Niemann 1860).  The German chemist Carl Schorlemmer (1834–1892) described the relationship between coca and its derivative cocaine in his text A manual of the chemistry of the carbon compounds, or, Organic chemistry (1874): “Cocaine (C17H21NO4) is the active principle of the coca-leaves.”  Richard Willstätter (1872–1942), the German who was awarded the 1915 Nobel Prize for Chemistry for studies of the structure of plant pigments, first synthesized and elucidated the structure of the cocaine molecule (Willstätter and Ettlinger 1903).  

       Vassily von Anrep (1852-1927), a professor of forensic medicine and a Russian statesman, had a major early influence in development of cocaine as a local anesthetic by describing its pharmacology through detailed studies in different species.  The contribution of von Anrep tends to be forgotten among other notables as Koller, Freud and Halstead who published in either German or English instead of Russian and were practicing clinicians (Yentis and Vlassakov 1999).  Von Anrep was the first to inject cocaine subcutaneously into humans (himself) and report the anesthetic effect produced (von Anrep 1880; Liljestrand 1967): “It had been my intention after the animal experiments also to make experiments on  man.  Other  engagements have hitherto  prevented  this  and  the  animal  experiments  do  not  permit  any  practical  conclusions. In spite of this, I would like to recommend cocaine as a local anesthetic as well as for melancholics.”  The introduction of the syringe and hypodermic needle (Rynd 1845) and von Anrep’s preliminary observations presented an opportunity to extend attempts to produce local surgical  anesthesia with cocaine, the logical extension to prior experiments conducted with agents as morphine, chloroform, water, and hypertonic salt solutions. 

       Sigmund Freud (1856-1939) was inspired to examine the stimulating effects of cocaine on mood and energy after reading the paper, “The Physiological Effect and the Importance of Cocaine” (Bernfeld 1953) by Theodor Aschenbrandt, a German army physician, who administered cocaine to Bavarian Army soldiers in 1883 during their maneuvers.  Aschenbrandt reported that the drug reduced fatigue and enhanced the soldiers’ endurance during drills, including such phrases as: “. . .increase of all mental powers. . . increase of the capacity to endure strain. . . suppression of hunger.”  As a result, Freud began studying the effects of cocaine in a different manner than surgeons would subsequently, primarily focusing on the effects of the drug on the emotional realm, using himself and others he knew and loved as his subjects (Freud 1884; Bernfeld 1953; Yentis and Vlassakov 1999).   He describes his findings in Über Coca, a paper promoting cocaine as a treatment of everything from depression to morphine addiction (Freud 1884):

       “. . . exhilaration and lasting euphoria, which in no way differs from the normal euphoria of the healthy person… You perceive an increase of self-control, possess more vitality and capacity for work…  In other words, you are simply normal; and it is soon difficult to believe that one is under the influence of any drug… Long-lasting, intensive mental or physical labor is performed without fatigue… You are able – on demand – to eat well and without disgust, but you have the clear impression that the meal was not required… This effect of hardening you against work… is enjoyed without any of the unpleasant aftermaths which accompany exhilaration through alcoholic means.  Absolutely no craving for further use of cocaine appears after the first, or repeated, taking of the drug; rather you feel a certain unmotivated aversion to it.”

       The last sentence now seems apocryphal in the context of current understanding of addiction (Martin, Weinberg and Bealer 2007). 

       The  introduction  of  cocaine  as a local  anesthetic was in ophthalmology by Carl Koller  (1857–1944),  a young physician in Vienna,  whose  interest  dates to the spring of 1884 when his friend and colleague Freud invited  him  to collaborate on studies of the effect of cocaine on muscular strength and fatigue using the hand dynamometer (Liljestrand 1967).  Work on cocaine quickly progressed to pioneering studies that involved giving the drug to others for putatively therapeutic effects.  A friend of Freud and Koller, the eminent physiologist Ernst von Fleischl-Marxow (1846–1891) had an amputation of his thumb and subsequent unbearable pains at the site.  Fleischl-Marxow started to use and became addicted to morphine and heroin.  His friends were convinced that cocaine would be useful as a treatment for Fleischl-Marxow’s morphine addiction.  The result was that he proceeded to fall even deeper into the abyss of addiction and eventually relapsed and began using morphine again until his premature death at the age of 45 (Liljestrand 1967).  A rival psychiatrist Friedrich Albrecht Erlenmeyer (1849–1926) described cocaine as the “third (presumably after morphine and alcohol) scourge of mankind” as sad outcomes occurred in many others (Goldberg 1984). 

       The well-known American surgeon William Stewart Halsted (1852-1922), one of the four founding professors of Johns Hopkins Hospital, accomplished pioneering surgical research with cocaine soon after he discovered the work of Koller.  Within two years, Halsted performed nearly 2,000 operations using cocaine as a local anesthetic, having established the principle of nerve block anesthesia (Olch 1975).  In the process of experimenting on himself, Halsted became addicted.  On one occasion, according to myth, as Halsted was attempting to demonstrate an operation to colleagues, his tremor was so severe that he could not continue the procedure and was forced to leave the operating room in disgrace (Goldberg 1984).  Despite needing periodic admissions to the Butler Hospital in Providence, Rhode Island, for withdrawal therapy, Halsted had a distinguished career in academic surgery, implementing creative and innovative surgical procedures and training subsequent leaders of the field (Bett 1952; Blalock 1952).  Fortunately, William H. Welch (1850–1934), the first dean of the Johns Hopkins Medical School, was able to take Halsted into his Baltimore house and thereby allowed him to continue to contribute to American surgery.  Halsted turned to daily morphine use in a futile attempt to “cure” his cocaine addiction as he had ready, unrestricted access to inexpensive, high-grade morphine in the surgical operating room (Martin and Finlayson 2012).  The historical lessons from the lives of Fleischl-Marxow and Halsted emphatically convey the simplistic and fallacious conceptualizations of addiction historically, namely that the disorder was caused by the drug alone, not the person who self-administers the drug and their circumstances (Martin, Weinberg and Bealer 2007).

       A quotation from the British and Colonial Druggist (Anonymous 1886) encapsulates the significance of cocaine in modern surgery: “The valuable alkaloid cocaine, whose properties as a local anæsthetic have created almost a revolution in ophthalmic and other branches of surgery.” However, the debate about whether cocaine was otherwise beneficial or harmful has continued, exemplified by the following discussion (Bosworth 1895): 

       “…. I only venture to ask the question, Is there a cocaine habit, and, if there is, how dangerous a habit is it and how great a slavery? …I have used it indiscriminately and on a very large number of cases… I have made a pretty large and thorough investigation of the action of cocaine, by way of experiment on myself…  I have failed to see anything in the action of cocaine which produced that peculiar craving which is necessary to constitute the habit.  There are certain things which are characteristic of enslaving drugs.  One is universal… that it creates a tolerance.  Opium, hashish, and arsenic, as is well known, create such a tolerance that, as the habit increases on one, increased doses become necessary to procure the desired effect. …more noticeable in cocaine… is that its use creates a susceptibility – the more one takes cocaine the less cocaine it requires to produce the desired effect.  Another characteristic action of an enslaving drug is that its intoxicating effects are followed by a reaction.  This is not characteristic of cocaine, although I should say that in my own experience, after experimenting with it for some months, I found that the stimulating effects which it first produced were followed by a sense of depression afterward, but only after I had experimented for quite a while.  Another feature of an enslaving drug is that it creates a craving, an appetite which cannot be resisted. This, I think, is not a characteristic of cocaine…  A still further feature in regard to cocaine… is that if one does acquire a liking for the drug the continued use of it will serve to overcome the appetite… the pleasurable stimulation decreases in amount, and sooner or later the time comes when the use of the drug ceases to be a pleasure – I mean by this the use of the drug in large amount… The prolonged use of small quantities of cocaine may, perhaps, not produce this effect…  Among my own patients I know of a number of instances where it has been used in moderation through periods of five, eight, and even ten years, without producing unpleasant effects and without creating a habit.  …many persons addicted to morphinism took up the use of cocaine with the hope for relief.  …my experience would suggest that the combination of opium and cocaine creates a far more dangerous habit than opium alone, and I am disposed to think that many so-called cases of cocaine habit are the result of a combination of the two drugs. 

       Whether its use hypodermically is attended with any additional changes, I cannot say.”

       Thus, despite clear behavioral toxicity from cocaine in some who conducted scientific experiments with the alkaloid, few believed that cocaine truly represented a serious risk to mental health and research turned to the pharmacology of cocaine to understand its efficacy in surgical anesthesia.  

       Langley and Dickinson (1890) showed that cocaine directly applied reduces the irritability of nerve fibers and Dixon (1904) proposed its selective effects: “Cocaine locally applied to nerve fibres picks out and paralyses some fibres before others; sensory before motor, vagal fibres conducting upwards, before those conducting downwards, vaso-constrictor fibres before vaso-dilator, broncho-constrictor before broncho-dilator.”  Cocaine was found to affect electrochemical conduction between neural cells (Dale 1935) and specifically altered effects of adrenaline  (Burn and Tainter 1931).   

       Concern about behavioral consequences of cocaine use did not cease; both acute and chronic toxicity were reported, including hallucinations (Anonymous 1889), addiction (Anonymous 1925) and “its demoralizing effects” (Bose 1902).  The mixed emotions concerning this drug were conveyed in the 1977 lyrics made famous by Eric Clapton who thought he had kicked a serious heroin habit and was heavily using cocaine and alcohol with the attitude that he could manage his addiction and quit at any time – he just didn't want to – so he could sing objectively about a drug that was consuming him, before the associated dangers were eventually recognized:

       “If you want to hang out/ You've got to take her out/ Cocaine/ If you want to get down/ Down on the ground/ Cocaine/ She don't lie/ She don't lie/ She don't lie/ Cocaine// If you got bad news/ You want to kick the blues/ Cocaine/ When your day is done/ And you wanna ride on/ Cocaine/ She don't lie/ She don't lie/ She don't lie/ Cocaine” (Cale 1977)

       Even the authorative pharmacology textbook of its time asserted (Jaffe 1970): “Cocaine abuse is now uncommon in Western countries, although the chewing of coca leaves is still common among Peruvian Indians of the Andes.” 

       In the early 1980s, the romance concerning this “sophisticated” drug vanished in a “snowstorm” of white powder overwhelmeding the western world (Byck 1987).  The American Psychiatric Association had not listed cocaine dependence in the third edition of their Diagnostic and Statistical Manual of Mental Disorders (APA 1980) because it was believed that neither tolerance nor withdrawal was characteristic of its use.  With the rapid increase in prevalence of pathological use of cocaine in the 1980s and striking association with other psychiatric disorders, it became apparent that this decision was sadly mistaken (Gawin and Kleber 1986; Grant 1995).  

       Research on cocaine changed precipitiously from its original focus on anesthetic properties to the neuroscience of cocaine-induced euphoria, the powerful rewarding effects of self-administration, influence on learning and physical and behavioral toxicity (Drake and Scott 2018).  It was demonstrated that presynaptic neuronal reuptake of dopamine by the specific dopamine transporter correlated with the reinforcing effects determined by self-administration of the drug (Ritz, Lamb, Goldberg and Kuhar 1987; Kilty, Lorang and Amara  1991).  Cocaine became central to neuroscience research during the “Decade of the Brain (1990 to 1999),” so designated as part of an effort of the National Institute of Mental Health to enhance the public awareness of brain research, which culminated in recognizing addiction as a brain disease (Leshner 1997).  The impetus for investigating the brain effects of cocaine have continued as a particularly destructive member of the stimulant class of drugs (Cassidy, Carpenter, Konova et al. 2020).



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March 25, 2021