An Anatomy of Addiction

by Howard Markel

  IN A MATTER OF TIME, thanks to more and larger self-injections of morphine, Fleischl-Marxow watched his life sink with the force of a lead bucket dropped into a lake. His was an addiction that was becoming increasingly common and was often provoked, if not caused, by physicians. Most of these medical doctors were well-intentioned and merely hoped to alleviate pain without a wide menu of therapies to do so. When it came to the effective control of severe pain, from antiquity through the nineteenth century, the options were limited to the highly habit-forming opium and, later, morphine and its pharmacological relatives.

  Opium was the first global pharmaceutical agent in the history of medicine. It is a sticky, bitter brown sap produced by the poppy (Papaver somniferum), a red wildflower that flourishes in Turkey, Afghanistan, China, India, and the Middle East. The plant may have originated along the western Mediterranean near southern France and Italy. By the Roman era, however, it had been transplanted in Egypt, and its use as a pain medication soon spread from the Middle East to Asia and Europe. Although highly valued by physicians of the Middle Ages, opium fell out of favor, its use in Europe declining precipitously during the Renaissance and the Inquisition. Beginning in the early sixteenth century, however, the seafaring Portuguese reaped great fortunes by importing opium from India. Britain’s expanding imperial influence in India during the seventeenth and eighteenth centuries, its growing wariness of and competition with nearby China, and a burgeoning opium trade ushered in the infamous Opium Wars of the nineteenth century. During the mid-1800s, opium was, once again, the doctor’s drug of choice for treating all forms of severe pain.

  For example, in 1860, the Harvard Medical School professor and literary superstar Oliver Wendell Holmes Sr. described the dangerous purgatives, emetics, and other industrial-strength agents then widely in use in the United States: “If the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind—and all the worse for the fishes.” The only agents Dr. Holmes exempted from this water dump were opium, “which the Creator himself seems to prescribe,” wine, “which is a food, and the vapors [ether] which produce the miracle of anesthesia.” Holmes was hardly alone in ascribing to opium a divine conception.

  Even more potent and convenient to use was morphine, the active alkaloid compound chemically derived from opium or poppy sap. A German pharmacist named Friedrich Wilhelm Adam Sertürner was the first to isolate the alkaloid, in 1803; he called it “morphium” after Morpheus, the Greek god of dreams. The drug was produced and mass-marketed beginning in the 1820s. Morphine’s popularity and profitability eventually inspired pharmaceutical manufacturers to introduce synthetic versions of the drug, beginning with codeine, in 1830, and, in 1898, heroin. Especially in the decades after the development of the hypodermic needle and syringe in 1853, there was an explosion of doctors freely prescribing and patients readily taking it. Many of the latter, unfortunately, became addicts.

  A superb example of the physician-created morphine addict of this era was presented in Eugene O’Neill’s Long Day’s Journey into Night. The playwright’s mother, Mary Ellen, first encountered opiate narcotics after a difficult pregnancy and the delivery of Eugene in 1888. Mrs. O’Neill fell into a serious postpartum depression, and within months her well-intentioned doctor had inadvertently transformed the grieving woman into a full-blown addict. In O’Neill’s play, Mary Tyrone, the character based on his mother, suffers relapse after relapse, no matter how hard she tries to abstain, much to the consternation, disappointment, and disgust of her husband and two sons.

  Interestingly, morphine addicts who self-injected the drug or sipped bottles of laudanum considered their habit to be more legitimate and less problematic than those who smoked opium in dens of iniquity. Regardless of the mode of administration, however, physicians at the close of the nineteenth century grew increasingly concerned about the cases of “opium invalidism” or “morphinism” that they were creating on an ever-increasing basis.

  ALTHOUGH MORPHINE CAN BE TAKEN orally or rectally, most avid addicts soon abandon these routes. This is because the drug is poorly absorbed by the gut and rarely produces the type of euphoric experience addicts crave. Some people will sniff it or smoke it in an opium pipe or cigarette. But the best way to consume the drug is to inject it into one’s veins using a hypodermic syringe. “Shooting up” gives these psychoactive molecules free rein in the bloodstream, so that more of the dose is quickly available to the brain, where the action is. Once a dose crosses the blood-brain barrier, it interacts predominantly with mu neuroreceptors, the same receptors that interact with the naturally occurring painkillers avid athletes know as endorphins. Opiates reinforce their power by inducing the increased release of dopamine, one of the central neurotransmitters the brain uses to interpret pleasure. Such chemical manipulations bring on a rapid relief from physical and even psychic pain—an indifference to it, really—even though the recipient is often awake and conscious. As the late comedian and heroin addict Lenny Bruce once said about his frequent drug-induced swoons, “I’ll die young but it’s like kissing God.”

  The so-called rush of morphine, opium, and heroin begins shortly after its injection. One of the first signs is the rapid constriction of the pupils. As those black dots dominating the eyes grow smaller and smaller, practically to pinpoints, one is less able to accommodate light and visual cues. So, too, does the outlook of an individual transform from an outward glance into an inward and transfixed stare. Warm sensations in the stomach progress to erotic stirrings and tingling in the genitals; the feeling has been described as better than the most extraordinary of sexual orgasms. Once the sensual fireworks subside, however, a stage even more highly coveted by addicts emerges, a first-class, high-speed ticket to temporary oblivion. Time appears to come to a halt and the junkie can pose as still as an accomplished yoga practitioner: silently sitting or lying on the floor, hugging his knees, or crouched in a fetal position. For the next few hours, the opiate-dominated mind is embraced in a silky, dreamy envelope of comfort that promises escape from the hardships, stresses, and trials of daily life.

  There are, of course, many negative side effects to opiate agents. Taken in excess, they constipate by retarding the movement of the gastrointestinal tract; for some people, these drugs can induce outright nausea and vomiting. At too high a dose, or overdose, morphine and its relatives profoundly depress the impulse to breathe by lulling the brain’s respiratory center into total complacence. Normally, this neurological center closely monitors levels of oxygen and carbon dioxide in the blood and, in response, sends messages to the lungs to breathe faster and deeper or slow and shallow, depending on what chemical mix it discerns. Under the influence of opiates, however, the brain’s oxygen receptors simply take a holiday. The subjective experience of the addict, as he delays taking each succeeding breath for just a bit longer than the last, is an intoxicating game of anticipation. As the level of carbon dioxide in his blood rises, he tumbles into an ecstatic but deadly bliss called narcosis. Such physiological perversion, incidentally, is one of the major reasons why the coda to so many opiate overdoses is death by respiratory failure.

  Long-term abuse of morphine and its pharmacological relatives essentially resets the rheostats of the brain. And because its frequent use leads to a rapidly increasing tolerance—meaning you need more and more drug to achieve the same desired results—a profound physical dependence rears its ugly head whenever the addicted body perceives that it is not getting enough of the stuff it craves. Ramped-up versions of restlessness, irritability and depression, anxiety, panting, cramping, insomnia, explosive diarrhea, intense aches and pains: these are the symptoms of withdrawal that most morphine and heroin addicts avoid like the plague and that every young physician learns to diagnose the moment a withdrawing patient enters an emergency room.

  AS HE SEARCHED FOR a medicinal agent to rid Fleischl-Marxow of his morphine addiction, Freud hit upon the idea of trying cocaine. One of the earliest records of thi
s therapeutic misadventure is documented in a letter Sigmund wrote to his Martha on April 21, 1884. That evening, he was assigned to cover the main hospital’s patient reception desk on what must have been a slow night. Instead of being swamped with composing the long and careful case histories that accompanied the admission of patients, the devoted Sigmund described his latest findings about cocaine’s alleged therapeutic powers:

  I am also toying with a project and a hope which I will tell you about; perhaps nothing will come of this either. It is a therapeutic experiment. I have been reading about cocaine, the effective ingredient of coca leaves, which some Indian tribes chew in order to make themselves resistant to privation and fatigue. A German has tested this stuff on soldiers and reported that it has really rendered them strong and capable of endurance. I have now ordered some of it and for obvious reasons am going to try it out on cases of heart disease, then on nervous exhaustion particularly in the awful condition following withdrawal of morphine (as in the case of Dr. Fleischl). There may be any number of other people experimenting on it already; perhaps it won’t work. But I am certainly going to try it and, as you know, if one tries something often enough and goes on wanting it, one day it may succeed. We need no more than one stroke of luck of this kind to consider setting up house. But, my little woman, do not be too convinced that it will come off this time. As you know, an explorer’s temperament requires two basic qualities: optimism in attempt, criticism in work.

  Elsewhere in this letter Freud demonstrates mastery of the extant medical literature, in English, French, and German, on the subject of cocaine. For example, he refers to the same article by Italian neurologist Paolo Mantegazza that so fascinated Angelo Mariani, the coca-wine king; it reported how cocaine enhanced strength and sexual potency among the Peruvian Indians who chewed coca leaves well into old age. He also describes a well-regarded 1883 medical report written by the German physician Theodor Aschenbrandt, suggesting that cocaine be prescribed for soldiers to improve their performance on the battlefield.

  Sigmund Freud at the time of writing Über Coca, 1884. (photo credit 4.4)

  Even more intriguing to Freud were a series of clinical papers published in George Parke’s house organ, the Therapeutic Gazette. In 1878, an American physician named W. H. Bentley described successfully treating a patient addicted to the “opium habit” with coca. Two years later, in 1880, Bentley reported his success in treating both opium and alcohol abusers with cocaine. With the twenty-twenty vision of historical hindsight, it is easy to shake one’s head at such a harebrained theory. Substituting one addictive drug for another was a common medical means of treating substance abuse in the late nineteenth century and, in fact, remains so to this day. It is impossible to give an accurate number of how many morphine addicts were unwittingly turned into cocaine addicts by well-intentioned physicians during this era; similarly, alcoholics were often prescribed morphine to the point of addiction and, later, cocaine and even nicotine to help them kick their drinking habits. At the dawn of doctors’ recognition of addiction as a disease, what all these games of medical musical chairs most reliably did was to create “new and improved” addicts.

  THE GREAT MICROBIOLOGIST Louis Pasteur declared that when it came to conducting scientific research, “chance favors only the mind that is prepared.” History shows that desperation can be a stimulant to such inspired activities as well. Sigmund Freud first encountered cocaine when his medical-career blues were playing cacophonous riffs in his head. Everything he worked for or aspired to seemed so tentative, so out of reach. Like Moses, the biblical figure who fascinated him throughout his life, Sigmund must have felt as if confined to Mount Nebo. He could see the Promised Land, which for him was a professorial appointment at the Vienna Medical School, but it looked as if he would never get there. In late May 1884, he reported to Martha about a meeting with his former teacher Hermann Nothnagel; the tête-à-tête was hardly encouraging. Writing about the conversation as if it were a one-act play, Sigmund recorded several of the internal medicine professor’s deflating observations, none more cutting than the comment “You know how hard it is to get along in Vienna, how hard our colleagues work from morning to night and still barely eke out a living.” Nothnagel also made a far from appealing offer: “I could give you some recommendations to Buenos Aires, where a former assistant of mine has a practice; or to Madrid, where I have any number of connections.”

  The surgeon general’s catalog entry on cocaine, 1883. Freud consulted this volume when beginning to write Über Coca. (photo credit 4.5)

  Sigmund quickly dismissed this depressing conversation because he was so busy looking after Fleischl-Marxow. On the nights he sat at his friend’s bedside, “every note of the profoundest despair was sounded.” As he worriedly wrote Martha: “I admire and love him with an intellectual passion, if you will allow such a phrase. His destruction will move me as the destruction of a sacred and famous temple would have affected an ancient Greek.”

  In May 1884, Freud explained to Fleischl-Marxow his idea about trying cocaine as a means to break the surgeon free from morphine. Fleischl-Marxow eagerly consented and embarked on a path that made him, quite possibly, the first morphine addict in Europe to be treated with this new therapeutic. The initial results were nothing short of miraculous. During the first three weeks of the “cocaine therapy,” Fleishel-Marxow’s morphine intake drastically fell to minute doses.

  Sadly, his condition soon plummeted. One night several weeks later, Freud; Sigmund Exner, Brücke’s other assistant; the neurologist Heinrich Obersteiner; and Fleischl-Marxow’s physician, Joseph Breuer, visited Fleischl-Marxow’s apartment only to find the door locked. The four men eventually procured a master key from the landlord. Once inside, they discovered their beloved colleague writhing on the floor, unwashed, naked, and delirious from pain. After the administration of large injections of morphine, Fleischl-Marxow finally collapsed into a narcotic-induced sleep. A few days later, the surgeon Theodor Billroth attempted an electrical stimulation of the stump, with disastrous results.

  By now, Fleischl-Marxow was consuming more than a gram of pure cocaine a day, along with enormous amounts of morphine. Addicts who mix opiates and cocaine enthusiastically endorse this combination because it produces a far more stunning high than either agent can produce alone. Following an injection of the ecstasy-producing morphine, Fleischl-Marxow added a chaser of cocaine to inspire a rush of electric-like waves of pleasure throughout his body. In the time span of less than three months, Fleischl-Marxow spent 1,800 marks (more than $3,300 in 2010) on cocaine hydrochloride, a sum that was a hundred times greater than Sigmund’s outlay of cash for cocaine during the same period. This does not even account for the money Fleischl-Marxow was regularly spending on his multiple daily fixes of morphine.

  Money for drugs aside, there was a higher price to pay. Eventually, Fleischl-Marxow’s copious substance abuse brought on severe fainting spells, convulsions, insomnia, hallucinations, and increasingly odd behaviors. As his addiction raged, his brain demanded more doses of the very drugs that were killing him. What followed were many more crisis-filled nights when Sigmund was urgently called to Fleischl-Marxow’s flat to nurse his drug-addled friend, only to repeat the whole horrible affair again the next evening. On June 4, 1885, Sigmund discovered Fleischl-Marxow in a state of “delirium tremens with white snakes creeping over his skin”—a result of cocaine intoxication and psychosis. Freud recalled it as “the most frightful night he had ever spent.” Although Sigmund predicted that his friend would live only another six months, it took six years before this “Greek temple” of a man was dead. A guilt-ridden Sigmund kept a photograph of Fleischl-Marxow hanging on the wall of his study for the remainder of his life.

  IN THE DAYS IMMEDIATELY FOLLOWING his initial “cocaine success” with Fleischl-Marxow, however, Freud was absolutely convinced that cocaine would prove to be a valuable therapeutic for addiction, depression, and neurasthenia, an exhausting condition defined by late-nineteenth-cen
tury physicians as an ambiguous type of nerve-cell fatigue. It was, unfortunately, an erroneous theory he would hold for some time even after Fleischl-Marxow’s descent, and with strikingly bad results. Soon after administering the first restorative doses to his friend, Sigmund set out to write the definitive monograph on cocaine. This project was conducted with the encouragement of the temporarily stable Fleischl-Marxow, who insisted that Sigmund get his findings into print as soon as possible.

  In order to produce more scientific data, however, Sigmund needed more cocaine. Consequently, he made a significant monetary investment by ordering a gram of cocaine hydrochloride from the Merck Company of Darmstadt. Like its American counterpart, Parke, Davis and Company of Detroit, Merck advertised its product with authoritative reviews on cocaine that were widely distributed to German physicians and, a few months later, American doctors. In one 1884 publication, for example, Merck methodically describes cocaine’s molecular structure, chemical properties, and physiological effects in animals ranging from puppies to humans, stipulating that all of the experiments reported, “without exception,” were conducted using “ ‘Cocain mur. Solut. Merck,’ ” and noting that “only for these are the doses and action, as above stated, to be relied upon.” Before long, Dr. Freud became a regular customer of the Merck firm.