Drug Abuse

In order fully to appreciate the causes which have led to the present widespread chronic use of opium and its derivatives, it would be necessary to dwell at length on the early history of its use and to trace through a long period,—at least the whole of the present era—its development, the growing cultivation of the drug in the Near East and later in the East, the transmission of the knowledge of its medicinal value to new countries and the development of the trade and commerce necessary to supply the growing demand along with the sordid motives which all too frequently foisted the product upon new markets for other than medical uses.
In the present study, however, as a practical measure we have had to confine ourselves chiefly to the latter half of the nineteenth century, when what appears to have been an unprecedented growth in the use of opium and opium products took place. Nevertheless, in order to give the reader some idea of the early unrestricted use and popularity of the drug prior to the beginning of the last century as a factor in the causation of its present widespread use, it is necessary to give a brief sketch of the history of opium and its various preparations as well as of the early development of their therapeutic use.
From the earliest records to which we have had access, opium and certain other narcotic drugs—mandragora, hyoscyamus, hemlock, lettuce and others—are among those known to have been used in medicine. A further search doubtless would show that the first knowledge concerning them is lost in remote antiquity. A. R. Neligan, in his book 1 on the opium question, states: "The earliest known mention of the poppy is in the language of the Sumerians, a non-Semitic people who descended from the uplands of Central Asia into Southern Mesopotamia, there to found a kingdom some five or six thousand years before the birth of Christ."
Presumably Neligan has this information from Doctor R. Campbell Thompson,' the archeologist whom he mentions as the author of an "Assyrian Herbal." We have consulted Thompson's translation of the Assyrian Medical Tablets.* These tablets date to the seventh century B. C. and he states they are copies of older texts judging from their similarity to medical tablets found at Ashur, which are some centuries earlier. In a list of 115 of the most commonly mentioned vegetable drugs, opium is mentioned 42 times, which gives it the thirty-third place in frequency of mention. Thompson quotes the following: "Early in the morning old women, boys and girls collect the juice by scraping it off the wounds (in the poppies) with a small iron scoope, and deposit the whole in an earthen pot." He comments that nothing seems to have changed in the collecting of opium. In Arat Pa. Pa, which Thompson gives as the Assyrian for juice of the poppy, he points out a possible origin for papaver.

Neligan goes on to say that:
"It does not require a great stretch of imagination to suppose that even in the days of the Sumerians, or the early Babylonians, some of their neighbours, living in the future home of the Persians, had learned of so striking a drug as opium from them. It is more than probable that the ancient Persians obtained it from Assyria or from Babylon, just as they acquired much of their civilization through their conquests of those States. Nevertheless, it is not apparently until the sixth century A. D. that opium was mentioned in a Persian text. However, the early Persians left no literature other than their sacred books."

Through the courtesy of Professor R. P. Dougherty, in charge of the Babylonian Collection at Yale University, we are informed that the Sumerians must have known of opium as they had an ideogram HUI.. GIL which signified this drug. In the medical tablets, above referred to, translated by Thompson, HUL. GIL occurs repeatedly and we are informed by Professor Dougherty that the Assyrians borrowed many ideograms from the Sumerians and used them interchangeably with their own words. The following is quoted from a letter received from Professor Dougherty:

"I should say that the basic meaning of the sign HUL is `joy,' rejoicing.' GIL as a single ideogram represented a number of plants, but its meaning in the ideogram for 'opium' is difficult to determine with exactness. It may be suggested in a very tentative way that the Sumerians in their system of pictographic writing endeavored to depict the power of opium to produce a sense of delight or satisfaction."

Professor Dougherty says that the ideogram HUL. GIL cannot be definitely dated, but that it probably goes back to the fourth millennium B. C.

From the best obtainable information the original home of the opium poppy was Mesopotamia, and it is not surprising, therefore, that both the Egyptians and Persians acquired knowledge of the drug early. According to Garrison,' the Ebers Papyri mention opium among approximately seven hundred remedies. The date of these papyri is thought to be about 1550 B. C.

A more classical mention of the drug occurs in the ninth century B. C. in Homer's Iliad where he describes the effect of the cup of Helen, "inducing forgetfulness of pain and the sense of evil." Many authors have quoted this passage. One of the best discussions we have seen is that of Michael Doering,e who quotes the opinions of Pliny, Justin, Macrobius, Aetius and others as to the exact nature of the draught.

According to Ernest Martin," Hippocrates ' (460-357 B. C.) recommended drinking the juice of the white poppy mixed with the seed of nettle for leucorrhea, and in another passage he recommends the use of the juice of poppy in "uterine suffocation" and describes the juice as "hypnotic (upnotikon) meconion."

In Francis Adams's ' translation of Paulus Aegineta, he states that Theophrastus g (370-286 B.C.) mentions the juice of the poppy and the method of gathering it, calling it "AnKedvtov" (meconion).
Virgil h (70-19 B.C.) mentions the sleep-bringing poppy in the Georgics and again in the Aenead.'
One of the best concise historical reviews of the use of opium is an article by David I. Macht 1 from which we have drawn freely in the following.
About the year 40 A.D., according to Macht, Scribonius Largus described the method of procuring opium from the capsules of the poppy and Dioscorides in the year 77 distinguished between the juice of the capsules and the extract of the whole plant, which he regarded as less active, describing "the preparation of a syrup of poppy or diakodion, which is the original of the syrup of poppies of the German and other Pharmacopeias to this day."
Later Pliny and Celsus among other Latin writers described the medicinal uses of opium. Galen also "spoke enthusiastically of the virtues of opium confections, and the drug was soon so popular in Rome that it fell into the hands of shop-keepers and itinerant quacks." Arabic physicians used it extensively. One of them, Abu-l-ali-ibnSina or Avicenna, recommended it especially in diarrhoea and diseases of the eye. This physician is said later to have died from an overdose of the drug.
It was through the spread of Mohammedanism by the Arabs that opium first reached Persia and later India. Macht continues:

"Serapio (about 1090) used it freely, and Maimonides and Averroes each wrote a treatise concerning the thebaic. . . .
"The earliest mention of opium as a product of India is by the traveller Barbosa, in his descriptions of the Mallaba coast in 1511. A Portuguese historian, Pyres, in a letter to Manuel, King of Portugal, in 1516, speaks of the opium of Egypt and Bengal. It is from Egyptian Thebes that we have the terms 'opium thebaicum' and the alkaloid thebain.
"Opium is supposed to have been brought to China first by the Arabs, who are known to have traded with the southern parts of the Empire as early as the ninth century. Later the Chinese began to import the drug in their junks from India. At that time it was used by them exclusively as a remedy for dysentery. It was not before the second half of the eighteenth century that the importation of opium began to increase rapidly through the hands of the Portuguese and a little later through the famous East India Company."

Describing the development of the therapeutic use of opium in Europe, Macht says:

"Since the time of Galen, the use of opium was continued in a disguised form in various concoctions and confections containing so many ingredients that the distinction between the important and useless could not be discovered. And the value of the drug was overlooked, except by a few brighter minds.
"The famous physician of the middle ages, Philippus Aureolus Theophrastus Bombast von Hohenheim, commonly known as Paracelsus (1490-1540), owed much of his success to the bold way in which he administered opium to his patients. He is said to have carried opium in the pommel of his saddle and called it the 'stone of immortality.' His followers were as enthusiastic as himself over the virtue of opium. Platerus of Basle in 1600 strongly recommended it and Sylvius de Is Boe, a famous Dutch physician, declared that without opium he could not practice. The celebrated chemist and physician, Van Helmont, about 1640, used it so frequently that he was called Doctor Opiatus, and Syden-
; ham about 1680 writes that 'among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium.'"

The four so-called officinal capitals, mithridatium, theriaca, philomum, and diascordium, were all compounds containing many more or less useful drugs and chemicals selected largely for powers accredited to them by superstition and each one probably owed much of its virtues to opium, one ingredient common to them all. Mithridatium is accredited to Mithridates the Great (about 100 B.C.) and became very popular as a panacea in Rome. Theriaca, a modification of mithridatium, was, according to the same author, invented by Andromachus, the physician of Emperor Nero.

"According to Galen, the virtues of this panacea were the following:
"'It resists poison and venomous bites, cures inveterate headache, vertigo, deafness, epilepsy, apoplexy, dimness of sight, loss of voice, asthma, coughs of all kinds, spitting of blood, tightness of breath, colic, the iliac poison, jaundice, hardness of the spleen, stone, urinary complaints, fevers, dropsies, leprosies, the troubles to which women are subject, melancholy and all pestilences.'"

In the early part of the nineteenth century, 1803-5, Serturner, a chemist. at Einbeck, discovered in opium an acid, meconic acid, and an alkaline base which he called morphium. This was the beginning of modern alkaloidal medicine. Robiquet in 1817 isolated narcotin and , in 1832 codein and in the same year Pelletier discovered narcein, thebain, papaverin, eryptopin, gnoscopin, xanthalin and other alkaloids followed as did their derivatives such as apocodein, heroin, dionin, peronin, etc.
When we realize that the chief end of medicine up to the beginning of the last century, was to relieve pain, that therapeutic agents were directed at symptoms rather than cause, it is not difficult to understand the wide popularity of a drug which either singly or combined so eminently was suited to the needs of so many medical situations. Each new compound or preparation acquired its devotees and in one form or another it was unquestionably the chief therapeutic agent for over two thousand years. That its use should spread beyond the ranks of the profession likewise is easily understood as the prototype of the patent medicine vendor of our own era doubtless relied upon its virtues as confidently and profitably as have his successors.
In addition to the above historical outline, it is interesting to note from the original writings of representatives of the various periods the influences tending to increase the popularity of opium. A few are given below:
Jones,2 in 1700, presents a volume on the physiologic effects of opium, proving to his own satisfaction that the evil effects are due entirely to its "noxious principle." On the title page appears the following:

"Shews (referring to what Jones claims to accomplish in the book) its noxious Principle and how to separate it, thereby rendering it a safe, and noble Panacea; whereof
"He shears the palliative, and curative use."

Although he realizes the dangers to health and life in the "long and lavish use" of opium from which the rosin or "noxious principle" has not been removed, he fails to appreciate the dangers of small but repeated doses and is convinced completely that opium from which the rosin has been removed is a safe and effective panacea.

"All, or most Physicians," Jones says, "unanimously agree, That Opium has such a noxious Quality that causes Vomitings, Hiccoughs, Distresses, Anxieties, Convulsions, chiefly at or about the Region of the Stomach; and that if it were freed from it, it would be the noblest of Medicaments; Who can otherwise imagine? seeing it is so excellent and universal a Remedy, as it is now used in the World, without such an excellent Preparation thereof, wherein the noxious Principle is separated from it."

"Of which Paracelsus says, that whoever shall enjoy it, will be a professor of no less Knowledge than Apollo, Machaon, or Podalyrius, tho' he was the greatest Master of Arcanas, Panaceas, etc., yet does he confess, 'That a Preparation of Opium stood him in stead, and perform'd his Business, when all his great Medicaments laird him: and that it will dissolve Diseases, as Fire does Snow; or uses words to the same Effect."

No drug has been applied to so wide a variety of uses as has opium nor has any given rise to so much discussion and controversy as to qualities and therapeutic indications, the form in which it is best given, and the manifold advantages of its use; scarcely a disease exists for which it has not been advocated enthusiastically by some writer. What are now recognized as properties of its individual alkaloids were discussed as contradictory actions long before the discovery of morphin. During the eighteenth century there was a prolonged controversy in which almost every writer on medical topics took part as to whether opium was a stimulant or a sedative. This controversy is well typified in a thesis by Hast Handy and in an inaugural dissertation by Valentine Seaman, both delivered in Philadelphia in 1791-2.
Handy 3 in discussing its action on the body concludes that it is a true stimulant. He describes its use by a well-known surgeon who "always took a considerable dose of opium previously to his performing an operation of any importance" and by a writer of the day who used it to sustain him for a literary. composition "which required an uninterrupted exertion of his mental faculties for more than 48 hours," adding that the opium "conducted him to the conclusion of his work with the same vigour and clearness of mind with which he had commenced it." As to its uses in diseases he states that it is employed in "those of greatest debility, and with great success," and quotes Drs. Cullen, Lind and Odier as to its value in the cure of intermittent fever. Quoting Dr. Rush, he states that it is valuable in "all those fevers or stages of fever where wine was safe or proper. I observed the happiest effects from it in the fevers of the military hospitals of the United States during the late war." He emphasizes its use in easing pain, in producing sleep, quoting Dr. Mead who says that "those who take it are so transported that they do not always sleep yet there is no happiness in the world that can surpass the charm of this agreeable ecstasy." He outlines its effect on the stomach, the pulse, the kidneys, in promoting sweat, and on the appetite and in review states that the diseases in which it is "proper" are "those of debility" including spasm, dyspepsia, violent hysteria, hypochondriasis, dropsy, tetanus, and fevers of the typhus kind and venereal disease.
It is significant that throughout his eulogy no mention is made anywhere of the dangers of continued use.
Seaman,4 on the other hand, while agreeing as to the efficacy of opium in pain and as a sopolific, denies that it is a stimulant in the true sense as Handy and others claimed, attributing its apparent stimulating effect to the fact that when this was observed the opium had been given in alcoholic solution. He advises its use as follows:—in allaying pain in venereal diseases, cancer, stone in the bladder, following fractures, and for nervous headaches. He states that it relieves palpitation, cures asthma and is of use in the "chin-cough, after the febrile symptoms have gone off"; also in the stomach for "pyrosis and gastrodynia" and for vomiting, while in the intestines it relieves cholera morbus, colic, dysentery, tenesmus and simple diarrhoea. It favors expulsion of calculi from the ureters and in the biliary duct and the return of incarcerated hernia. As to voluntary muscles it is useful in tetanus, in some epilepsies, and in convulsions, while in typhus fever he uses it for inducing sleep. He uses it also in acute rheumatism, intermittent fevers, smallpox and many other diseases. This author likewise fails to mention dangers of chronic intoxication or to caution against its continued use.
From the two preceding abstracts it is evident that however the schools of thought differed as to the modus operandi of opium their views limited but little their use of the drug in almost all therapeutic situations.

Smith,5 1832, in an inaugural dissertation on opium for the degree of Doctor of Medicine at the University of the State of New York, says:
"There is scarcely a disease in which opium may not, during some of its states, be brought to bear, by the judicious physician with advantage."

"Opium should never be exhibited simply to rouse the spirits, to awaken the fancy or to give a temporary exertion to brilliant wit, this practice is most deleterious. Neither should it ever be used, except to obviate some symptoms of disease, or for such other purposes as judgment sanctions. Opium should never be used as a substitute for the ordinary stimulus either of wine or spirits; for when it is thus used, it seldom fails to lay the foundation for a long train of morbid symptoms, which, sooner or later, terminate in all the wretchedness, which disease is capable of inflicting; yet this drug is in every day's use, and particularly among the better circles of society, and by the softer sex.
"Fearful of names, rather than of consequences, opium is continually resorted to by many of both sexes, but particularly by females, and these of the higher circles, as a substitute for the stimulus ordinarily afforded by gin or brandy. And hence the emaciation, and most of the long train of dyspeptic symptoms, and gastric derangements so commonly met with in persons in this class of society. But there is another class who resort to opium in some one or other of its forms, either from indolence, or carelessness, or both; I mean mothers, nurses, and those to whom are intrusted the charge of infants. The youthful, inconsiderate mother and the idle nurse, too frequently resort to opium to hush the infant's cries, which might have been done, by the ordinary and only best means of nursing.
"The gay and youthful mother, rather than forego the pleasures of a crowded assembly, or the gaudy charms of a dramatic scene, a single evening, not unfrequently commits the unfortunate infant to its cradle under the influence of opium, in the form, either of Darby's Carminative, the Paregoric Elixir, or Godfrey's Cordial, and even laudanum itself."

"But the injudicious use of opium is not confined alone to mothers and nurses, many practitioners of medicine are also culpable. Like calomel and jalap, which, because it is allowed to be useful in almost all cases, it is often forgotten that there are, nevertheless, many cases in which opium, like that prescription, is not admissible.
"In hope, however, that as the science of chemistry advances, it will continue to unfold even more minutely than it has already done, the hidden principle of activity, alike of many other agents of the Materia Medica, as of opium, we trust that error, like the dew, will vanish under the shining influence of improvement in the profession."

Here is seen appreciation of influences other than therapeutic requirements as factors in the spread of opium use. It was inevitable that a product so varied in its attributes, so potent in its effect, and so widely disseminated and easily procurable should be seized upon under one pretext or another. It is natural that the more advanced thinkers among the laity should turn to a drug whose virtues were so extolled, however erroneously, by the best medical minds of the day and that the unstable, neurotic, or otherwise constitutionally abnormal should avail themselves of its refuge. It is also natural that the writers of this period, impressed by the alleged mysterious and potent qualities of the drug, should introduce it in their works, thus stimulating among their readers a morbid curiosity that not infrequently led to hazardous experiments. At that time, in England, where doubtless through the opium traffic the drug was in more common use than elsewhere among European countries, a major period in literary achievement was ,in process of birth. It was not unnatural that among this group of intellectual adventurers were to be found some who through physical infirmity or for other reasons seemed peculiarly suited to succumb to the prolonged use of a drug whose stimulating and sedative qualities apparently were so satisfactorily blended. It was peculiarly unfortunate, therefore, that among them arose one whose personality makeup and intellectual gifts combined to induce him to apply his talent to the lauding of an agent which eventually accomplished his ruin. As a fortuitous influence originating neither in real therapeutic need nor in deliberate viciousness but rather in an unfortunate combination of temperament, ill-health, and intellectual gifts, none has been so far-reaching possibly as Thomas De Quincey's "Confessions of an English Opium-Eater," 1821. It is probable that even today of most of those who have come in contact with a considerable number of individuals suffering from chronic opium intoxication, there are few who have not known one or more who owed their first introduction to the drug to a perusal of De Quincey's sorry masterpiece. Not only has it influenced individuals of suitable psychologic make-up to fall under the sway of the drug but also it was the forerunner of a host of other morbid and ill-conceived creations on the part of misleading writers who have chosen to apply what mediocre or other gifts they have had to the stimulating of exploitable desires and weaknesses. This, what may be termed the educational influence, has continued to the present time as is evident to anyone familiar with the periodical or daily press.
An historic example of the influence of De Quincey's "Confessions" is cited in the Knickerbocker Magazine, 1842, by William Blair, who states in partial explanation of the causes leading to his chronic use of opium such as impaired health, ill-nourishment from poverty, overwork, and depression, that he turned deliberately to the drug to enable him to accept a position that had been offered him, as at the time he was too weak to work. He says:

"The strange confessions of De Quincey had long been a favorite with me The first part of it had indeed been given me, both as a model in English composition and also as an exercise, to be rendered into Patavinian Latin. The latter part, the 'Miseries of Opium,' I had most unaccountably always neglected to read."

De Quincey's influence was well recognized by a number of the medical writers who first began to warn both the profession and the public against the growing, widespread and injudicious employment of opium and its derivatives. Thus Calkins in 1871 6 states:

"De Quincey made his first essay upon opium during his student-life at Oxford. Some gastric derangement, sheltered under that broad-shouldered patronymic, dyspepsia, offered a plausible excuse; but back of this a more cogent incitement was at work, the longing felt for some sort of artificial excitement for occasions, and particularly in anticipation of the Saturday-evening opera. His maximum for the day, 8,000 drops, was attained by the eighth year—a nominal and putative rather than a precisely definite measure, as appears in a declaration recently made by his quondam-friend Sinclair, who had accompanied De Quincey time and again to the apothecary's in Edinburgh where stands Scott's monument, to see him toss off a wine-glass of laudanum and with a sang-froid as if the draught had been mere water.
"The autobiographer and essayist, author of `Suspira de Profundis' (ex Pro-fundis is meant), as also of 'Letters to Young men,' and the rest, was wont to herald every fresh volume of his 'farrago libellorum' with the pretentious announcement, 'By Thomas De Quincey, Author of Confessions of an English Opium-Eater.' On every successive title-page along with the conscious confession to an overshadowing infirmity, is thus paraded a palpable yearning after a notoriety that should preoccupy the public curiosity, rather than a precatory appeal, in arrest of judgment, to a lenient public sympathy. 'Is this a guide to them that sit in darkness, an instructor of the foolish?' He that `gropeth at noonday as in the night' renders but a dubious protection against the moral titubalions of inexperienced youth, who, if walking blindly, appear peradventure less blind than their leader, Quosque tandem?"'

Here and there during this period a few warnings of the dangers of the too free use of opium were sounded, even as early as 1700 when Jones recognized its dangers to health and life, warning against "a long or lavish use" but failing apparently to appreciate the dangers of small but repeated doses, while his work as a whole encouraged its employment. As a very gereral rule, however, the medical writings of the day overlooked or failed to emphasize the dangers of continued administration, so that the situation was already bad when the subcutaneous administration by means of the hypodermic syringe introduced an added factor of very marked importance and one which has continued to be felt up to the present time. As Kane 8 says:

"There is no proceeding in medicine that has become so rapidly popular; no method of allaying pain so prompt in its action and permanent in its effect; no plan of medication that has been so carelessly used and thoroughly abused; and no therapeutic discovery that has been so great a blessing and so great a curse to mankind as the hypodermic injection of morphia."

Nearly two hundred years before the hypodermic injection of drugs was practiced, Sir Christopher Wren, according to Macht? in 1656 first injected drugs intravenously. He employed a quill attached to a small bladder and injected dogs with opium and other drugs and a year later repeated the operation on human beings. Macht also states that J. D. Major, an English practitioner, employed this method in 1662 and others followed suit. Later there followed the epidermatic method, that of the direct application of the drug to the skin as in ointments and the endermic method of application to a surface denuded of epidermis by blistering or burning with caustics.
According to Roubinovitch 10 the next advance was made by Lafargue of Saint-Emilion in 1836 when he discussed before the Academie de Medecine the administration of morphin and other substances by
inoculation.
Alexander Wood of Edinburgh quite generally has received credit as the discoverer of the hypodermatic method of injecting drugs under the skin in liquid form. Kane says that Wood

. . . commenced the practice in 1843 and wrote upon it in 1855. Dr. Wood's priority in this matter has been disputed by Rynd, of Dublin, and Kurzak, of Vienna."

It seems certain, according to Macht, that Rynd was the first to use this method. At all events Rynd published in 1845,11 while Wood's first publication, according to Macht, was 1853.12 Macht says that the instrument devised by Rynd and described by him in 1861 13 operated by gravity through a hollow needle and that Wood employed a syringe made by Ferguson of London.
Kane also states that Drs. Isaac. E. Taylor and Washington claimed to have used practically the same method in 1839. He says:

"They made an incision into the skin and then injected the drug into the subcutaneous cellular tissue with an Anel's syringe, the nozzle of which was thrust into the cut."

He further states:

"The claim made by Dr. Taylor is unquestionably a sound and just one, it being supported by the testimony of Prof. Lewis A. Sayre and others, who saw these gentlemen carrying out the practice daily."

Commenting further on the development of the hypodermic syringe, Kane states:

"Dr. Wood's syringe-needle was not pointed, and had no lateral opening, it being necessary to incise the skin before introducing it. To Mr. Chas. Hunter, of London, is due, however, the highest praise of all . . . Hunter added the needle point, lateral opening, and made many other small but important improvements."

Undoubtedly Hunter did much to extend the use of the hypodermic in England, publishing many papers on its advantages and studying its effect on both man and animals. Others who endorsed it in England were 011iver, Bonnar and B. Bele. Its use was extended rapidly to the continent where it was received favorably by Montpellier, Behier, Courty, Richet, Trousseau, Herard, and Pravaz in France and by Scanzoni, Oppolzer, Graefe, Eulenberg, Erlenmeyer and Lorent in Germany and Austria. Pravaz improved the instrument and his name has been identified since with certain models.
According to Kane, Fordyce Barker of New York was the first to employ "the hypodermic syringe proper" in this country. He received one from Prof. Simpson while visiting in Edinburgh and used it here in May, 1856.
Macht gives to Ruppaner of Boston the credit of introducing the method into the United States, while Kane credits him with doing much to popularize and extend the practice. Ruppaner used chiefly liq. opii seditavus (Squibb), 100 drops of which equalled one grain of morphia while Wood employed Battley's solution, a preparation double the strength of the tincture of opium.
With the advent of hypodermic medication through the use of this instrument two new influences at once were brought to bear upon the development of the problem of chronic opium intoxication. One of these was the obvious advantage of this method of administration of therapeutic agents, such as the vegetable alkaloids, over mouth or other methods, as being more exact and more prompt in action and in requiring smaller doses. The other was the belief that with the administration of morphin through the skin the danger of the development of what generally was known as the "opium appetite" could be eliminated. It must be remembered that up to that time cases of the opium "appetite" or "habit" had developed through oral administration only and it was classed in the same category as other substances such as alcohol for which an appetite or liking or habit developed. This idea further may have been fostered by the use of alcoholic preparations of opium such as tinctures, which very commonly were used, or by the not infrequent taking of laudanum or other opium preparations in wine or liquor. It must be remembered also that at the time of these inventions and for many years thereafter biochemistry as it is understood today was quite unknown as were all of the other modern theories which have been advanced to explain chronic opium intoxication. Likewise the personality factor as interpreted by psychiatrists of today and the development of psychopathologic changes, resulting from the use of the drug with its strong appeal to certain temperaments, were all unrecognized and in the new method were seen only the more obvious advantages already mentioned. As a result the hypodermic use of morphin spread rapidly. As it became more common, hypodermic syringes were left with patients and practically every painful condition was an indication for its use. In America the instrument came into general use later than in Great Britain but its popularity was stimulated markedly during the Civil War. This was the first occasion when the instrument was available for the wholesale relief of pain.
It must not be supposed that during all this time no cases of chronic opium intoxication resulting from the hypodermic use of morphin were noted. As a matter of fact Wood's wife was probably the first individual to succumb to this method of administration, dying a victim of her husband's ingenuity. Other cases must have been noted but for one reason or another warnings of the dangers inherent in this method were very slow to come. The first record of warning as to the danger of hypodermic administration that we have found was made by Nusbaum 14 who, according to Allbutt,15 drew attention to the danger as early as 1864. In 1869 Parrish 16 refers to the growing popularity of this method of administration and cites a case whose chronic use of morphin dated from his introduction to the hypodermic syringe. In Allbutt's writings we are told that Hunter 17 also published a warning in 1869 and Allbutt himself in 1870 18 sounds another early warning.

From his statement we may conclude not only that the hypodermic was used for the relief of pain but also that it had become well and favorably known among certain groups for purposes of dissipation to such an extent that the fiction writers of the day adopted it or were employing it much as have certain sensational writers of our own time. Thus Allbutt states: 18
"Now that the hypodermic use of morphia is brought into sensational novels as a melodramatic device it may indeed be said to have reached the height of fashion. We may thank our stars if one of us he not seen ere long, syringe in hand, between Aspasia and Clodius in the windows of the Burlington Arcade."
The author admits that in his previous writings on the subject he has recorded the virtues of this admirable remedy and extended its application but states that it seems nevertheless "the duty of those who use so potent a medicine, to consider the full bearings of their practice and to make themselves as well aware of its dangers as of its virtues."
He states that little or nothing has been said of harm that may result from it and that among the numerous essays and records concerning the hypodermic use of morphia he cannot call to mind one in which its possible dangers have been considered, but he feels that "the time has come when the attention of the profession will be called to this less pleasant side of the account."
Injected morphia, he says, at first seemed different from swallowed morphia and no one had any experience of ill effects from it, but gradually he became convinced:
"that injections of morphia, though free from the ordinary evils of opium-eating, might, nevertheless, create the same artificial want and gain credit for assuaging a restlessness and depression of which it was itself the cause. Certainly, all the patients I have named fall off in the same way when the morphia fades from the system, and in all there is an indescribable depression and irritability which alone the morphia can relieve, and for which it is accordingly again and again administered. They are all satisfied that without the morphia the pain must return and will keep them in agony, and, when efforts are made to omit the dose, the pains do return until the fortitude of the patient is broken down, and the morphia is called for. At such times I have certainly felt it a great responsibility to say that pain, which I know is an evil, is less injurious than morphia, which may be an evil. Here is experience needed. Does morphia tend to encourage the very pains it pretends to relieve; or if not, does it at any rate induce in those who use it constantly, an artificial state which makes its further use a necessity? Are the subjects of morphia injections, that is, liable to become depressed, relaxed, irritable, and dependent upon a new habit of constant intoxication? If this be so, we are incurring a grave risk in bidding people to inject whenever they need it, and in telling them that the morphia can have no ill effects upon them so long as it brings with it tranquillity and well-being."

Calkins,19 1871, after describing the technique of opium-smoking mentions the use of the hypodermic needle but concludes that "any reliance placed upon this form of use, however, for its supposed comparative security, is likely to prove delusive."
While warnings such as these were being given, the medical journals of the day were full of enthusiastic descriptions of new successes in therapeutics through the hypodermic use of morphin and it is very doubtful if any painful condition to which the human race is heir escaped the list of those for which the drug was recommended.
In America following the Civil War the increase in opiate use was so marked among ex-soldiers as to give rise to the term "army disease" and today in more than one old soldiers' home are cases of chronic opium intoxication which date from this period. Crothers,2° 1902, states:

"Many veterans of the Civil War became morphinists to relieve the pain and suffering following injuries received in the service, and the addiction is often concealed to prevent the possibility of imperiling their application for pension. The theory obtains that morphine-taking is a wilful vice and the disabilities from its use should not be recognized by the Pension Bureau. . . . The sufferings and hardships growing out of the perils of war often react in illness, nerve and brain instability, and feebleness, and the use of morphine is a symptom of damage from this source which should be recognized as its natural entailment and sequel by the Pension Bureau."

Further reference to the influence of the Civil War is made in the
extracts quoted from correspondence published in the report of the Massachusetts State Board of Health in 1871.
Following such articles as that of Allbutt, other medical writers cautioned against the too free use of the hypodermic and against the dangers of leaving it with the patient or family. It gradually became
recognized by some to be a more dangerous method of opiate administration than any other.
McFarland,21 1877, states:

"If cases of opium inebriety occur as frequently in the private practice of other physicians as they have in my own, it is coming to be a serious matter, and a few words of caution, against the indiscriminate use of so active a drug, may be pardonable.
"Since the introduction of the hypodermic syringe, especially, there has been a noticeable increase in the frequency, as well as the severity, of the cases; and I wish to enter a protest against its imprudent use, and particularly against leaving it in the hands of patients or their friends, to be used at their discretion, or even allowing them to know that they can use it, except in the greatest emergencies; for once in their possession, and used for any considerable length of time, they will seldom discontinue it, and will soon be inquiring where they can get 'one of those things.' It is certainly a most valuable instrument in the hands of the discreet practitioner, and will reach cases which nothing else will, with a certainty and promptness which is very satisfactory; but it is too potent for evil, as well, to be trusted beyond his grasp."

Kane,22 1880, states:

"The danger of contracting this habit from the hypodermic use of morphia was recognized in the very infancy of the practice, but was scoffed at or disregarded until a few years ago, when the profession in Germany, England and America awoke, almost simultaneously, to a knowledge of the fact that the habit had become alarmingly common, and that it had been contracted, in the majority of instances, through the carelessness of the physician, who had taught either the patient or his friends how to use the instrument.
"Some of my correspondents, men of ability, and in large practice, express themselves as very skeptical of the truth of the statement that the morphia habit has ever been formed by the use of the drug hypodermically. Testimony from all parts of the civilized world settles this matter beyond question. Bartholow, from whose excellent little work I have so often quoted, says:
" 'The introduction of the hypodermic syringe has placed in the hands of man a means of intoxication more seductive than any which has heretofore contributed to his craving for narcotic stimulation. So common now are the instances of its habitual use, and so enslaving is the habit when indulged in by this mode, that a lover of his kind must regard the future of society with no little apprehension. It may well be questioned whether the world has been the gainer or loser by the discovery of subcutaneous medication. For, every remote village has its slave, and not unfrequently several, to the hypodermic syringe, and in the larger cities men in business and in the professions, women condemned to a life of constant invalidism, and ladies immersed in the gayeties of social life, are alike bound to a habit which they loathe, but whose bonds they are powerless to break. Lamentable examples are daily encountered, of men and women, regardful only of the morphia intoxication, and indifferent to all the duties and obligations of life, reduced to a state of mental and moral weakness most pitiful to behold.' "

Kane then gives the following precautions to be taken in order "for the patient to recover without any desire to continue the use of the drug":

"1. The drug in any form or in any manner should never be used in cases where the patients are of decidedly nervous temperament or when they are in a condition of neurasthenia, so long as some other drug can be found to accomplish the same end, even though relief be a little less rapid.

"2. In any case the drug should be used only in quantity just sufficient to obtain relief. It is surprising in how many cases decided relief from pain will result from the subcutaneous injection of morphia in very small doses (1/16 to 1/6 gr.), especially if the puncture be made deep into the muscular structure of the part.

"3. The earliest opportunity for decreasing the amount of the drug should be carefully watched for and the necessary gradual decrease in the strength of the solution be made.

"4. Where morphia is to be used for any length of time, atropia should be combined with each dose of it, in small amount (from 1/90 to 1/120 gr.) as Bartholow is of the opinion that the danger of contracting the habit is thus lessened.

"5. The patient should be kept in utter ignorance of what the solution contains, and of its strength. Under no condition whatever should the patient, his friends or attendants be instructed in the use of the syringe."

After outlining these rules for the prevention of addiction-formation, Kane mentions briefly conditions which have been found to be benefited by the hypodermic use of the drug. These he lists as follows:

Anaemia, Cerebral

Angina Pectoris

Asthma

Blepharospasm

Bronchitis

Cholera

Cholera Morbus

Cholera Infantum

Carcinoma

Cystitis

Continued Fevers

Convulsions, Hysterical

Cardiac Diseases

Chorea

Delirium-Tremens

Dyspnoea

Dislocations

Diabetes

Dyspepsia, Nervous

Diarrhoea

Emphysema

Epilepsy

Gastric Catarrh

Gastric Ulcer

Hepatic Colic

Hepatic Cancer

Hepatic Abscess

Insomnia

Incontinence of Urine

Itching

Laryngismus Stridulus

Lead Colic

Lumbago

Malaria and Malarial Neuroses

Mania and Insanity

Meningitis, Cerebro-Spinal

Muscular Spasm

Neuralgia

Nymphomania

Ovarian Neuralgia

Pleuritis

Pneumonitis

Pericarditis

Peri tpnitis

Polyuria

Renal Colic

Rheumatism

Shock

Spinal Irritation

Sprains

Tetanus

Uraemia

Vaginismus

Vomiting of Pregnancy

While others here and there issued similar warnings, it must be remembered that the great bulk of the medical profession practiced medicine more or less empirically, that interest in medical societies and medico-social problems was much less active than it is today, and that medical news like lay news travelled less rapidly and was disseminated less widely. Further, while here and there the more thoughtful and observant members of the profession noted the harm that was being done, they did not all write about it and such comments as they had to make doubtless were made within the small circle of their acquaintances rather than to larger groups. Meanwhile the ease with which pain could be relieved through the hypodermic administration of the drug, the time it saved the physician in his busy rounds, the contentment it brought the patient, and above all the all too common inclination to relieve symptoms rather than cause, contributed to increase the practice. Consequently throughout the period of the earlier warnings of its dangers the employment of this mode of administration was increasing by leaps and bounds wherever medicine was practiced. From the earliest warnings until 1900 the great majority of textbooks on the practice of medicine, materia medica, and therapeutics failed to issue any warning of the dangers of the hypodermic use of morphin.

In 1903 Roubinovitch 23 records his belief that

"the great majority of morphinists and morphinomaniacs owe their intoxication above all to the hypodermic introduction of the alkaloid of opium, which does not in any way exclude the possibility of reaching the same pathologic result as that of morphinophagia, a much rarer procedure.
"We can then say that the subcutaneous method, which constitutes one of the greatest acquisitions of modern therapeutics, has contributed considerably in ignorant and unpracticed hands, to the development of morphinism. It would be puerile to hold this method responsible for it ; everything depends on the persons using it."

Shortly after the end of the Civil War the smoking of opium, which had hitherto been confined in this country to the Chinese, began among the whites. According to Kane 23a a sporting character by the name of Clendenyn was the first white man to smoke opium in San Francisco in 1868. The second, Kane says, induced to try it by the first, smoked in 1871. He continues as follows:

"The practice spread rapidly and quietly among this class of gamblers and prostitutes until the latter part of 1875. at which time the authorities became cognizant of the fact, and finding, upon investigation, that many women and young girls, as also young men of respectable family, were being induced to visit the dens, where they were ruined morally and otherwise, a city ordinance was passed forbidding the practice under penalty of a heavy fine or imprisonment, or both. Many arrests were made, and the punishment was prompt and thorough.
"On this account the vice was indulged in much less openly, but none the less extensively, for although the larger smoking-houses were closed, the small dens in Chinatown were well patronized, and the vice grew surely and steadily."

As will be seen by consulting Table V, page 44, importations of smoking opium "entered for consumption" rose markedly in 1871 and never again touched the relatively low figures of preceding years, 1864 to 1870 inclusive, until 1884 when the extremely low figure of 1066 pounds was recorded, but as will be seen elsewhere this was the result of certain special factors.
The story of opium smoking in the United States is one which repeatedly has been told and which from time to time has been the subject of much public interest and of many official investigations. Further consultation of Table V will show that the peak in pounds imported was reached in 1883 when 298,153 pounds were entered for consumption. A second peak of 182,629 pounds was reached in 1903 and after 1909, in which year 118,508 pounds of smoking opium were entered for consumption, the importation of this form of opium entirely ceased and has never been resumed legally since.
Kane and other writers have described the rapidity with which the practice spread from San Francisco eastward involving practically every town and city in the country in its progress from the West to the East coast. The numbers of individuals who used opium in this form during the height of its popularity and before active law enforcement measures and other factors succeeded in controlling it to a large extent is not known. Various estimates have been made but obviously in a practice of this kind which was always frowned upon by the general public, as well as by official circles, no accurate figures could be obtained. From the amounts imported, presumably large numbers were involved. For the past ten or fifteen years, however, the smoking of opium has ceased to be a problem of any magnitude in the United States, though it is not a wholly extinct practice. It, however, must not be overlooked, in considering the development of the opium problem as we know it, that in many individuals still living the use of opium in other forms is the result of earlier experience with smoking opium. The equipment required, the odor of the burning drug and later its cost all combined to make relatively easy the closing of the places where the drug was used in this form, once public opinion and police activities were awakened.
The only measures employed for the control of importation of smoking opium before the passage of the Harrison Narcotic Act were those involved in the imposing of more or less heavy import duties, and, as will be seen by consulting Chapter XI, the importation figures varied from time to time as the import tax. was raised or lowered. Concurrently, however, with the lessening of imports, due to heavy taxes, as Hamilton Wright states, smuggling operations increased and while the legal importation ceased entirely, as has been stated, in 1909, smuggling of this form of opium continued and to some extent exists today. It is not inconceivable that taxation and police and other activities had less to do with the ultimate near-control of the practice of smoking opium in the United States than had the popularizing in the underworld of the hypodermic and the sniffing of heroin, forms of indulgence that were cheaper, more convenient, more adaptable to many surroundings, and far more easily concealed from friends, public and authorities.
Another influence which operated undoubtedly to extend the use of opium and its derivatives especially during the latter half of the nineteenth century was the patent medicine industry. It would be impossible to form any accurate estimate of the influence exerted by the widespread sale and use of nostrums containing opium, but that this influence was great and contributed in an appreciable degree to the habitual use of the drug is undoubted. It must be remembered that those who employed these secret remedies were for the most part
ignorant of drug dangers, sick, frequently in pain, and often suffering from some chronic malady and hence in a mental state which rendered them easy victims to the specious advertisements of the manufacturers. How widespread the custom of self-medication with patent nostrums became in this country is a matter of common knowledge. Newspapers and magazines were filled with fraudulent and misleading but seductive advertisements, while from billboards "pain-killers," "cough mixtures," "soothing syrups," "women's friends," "consumption cures," and a host of others, furnished a constant suggestion that could not fail to have its effect upon a considerable proportion of the population. The peak of the patent medicine industry was reached just prior to the passage of the federal Pure Food and Drugs Act in 1906.
Practically all remedies advertised for painful conditions, such as consumption, coughs and colds, pelvic troubles of women, cancer, rheumatism and neuralgia, as well as soothing syrups for babies, and diarrhoea and cholera mixtures contained opium or some of its products and depended principally on these drugs for such virtues as they possessed. It is not surprising that many persons became dependent on these preparations and later turned to the active drug itself when accidentally or otherwise they learned of its presence in the "medicine" they had been taking. Obvious and logical as was the influence of the patent medicine industry, it cannot be measured with any degree of accuracy and therefore must be accepted along with certain other influences such as the counter sales of the drugs themselves—equally immeasurable as a causative factor—as an extremely vicious and probably a very active influence. Many physicians who have treated numbers of cases of chronic opium intoxication in private practice mention instances of cases that owed their origin to the use of opium-containing nostrums.

One phase of the secret remedy evil which deserves special mention is that dealing with remedies for the so-called "drug habit." As was shown in various articles in the Journal of the American Medical Association,24 in the President's Homes Commission Report,25 in Samuel Hopkins Adams, "Great American Fraud" series 26 and elsewhere, these drug cures depended for their action upon the very drugs causing the condition for which the patient sought relief, or if not on the identical drug at least upon another derivative of opium. All that the patient gained was a change from one opium preparation to another at a greatly increased price.
It is not improbable that in this period of its development along with a better appreciation of the dangers of continued opiate administration and the influence of the Pure Food and Drugs Act with its attendant publicity, the extent of chronic opium intoxication would have been lessened appreciably except for the entrance of a new factor. It must be remembered that at this time textbooks on practice of medicine and therapeutics were beginning to include warnings against the indiscriminate use of opium, and that while twenty or even ten years before it was the exception to find any such admonitions, students of medicine around 1900 had a better opportunity to avoid the mistakes of their predecessors. Knowledge was becoming more widespread than before; the evils of opium-smoking had been brought forcibly before the public by periodicals and the press; and laws directed at the control of this form of opium abuse were being contemplated. In fact certain states had already legislated against opium dens.
Unfortunately, just at this period when more accurate and widespread knowledge and better methods of medical education might have tended to retard the growing use of opium, a most unfortunate influence became operative. Dreser in Germany in 1898 produced heroin or diacetylmorphin which was put out as a safe preparation free from addiction-forming properties, possessing many of the virtues and none of the dangers of morphin and codein, and recommended even as an agent of value in the treatment of chronic intoxication to these drugs. Probably no remedy ever was heralded so enthusiastically as was heroin. The prominent place held by opium derivatives in therapeutics, the constant calls on every physician to relieve pain and induce sleep with drugs, and the relative inadequacy of all substitutes for opium combined from the outset to stimulate the use of heroin. It was apparently the ideal preparation,—potent analgesic and sedative,—at the same time possessing other qualities highly desirable in certain ailments, above all freedom from the dreaded so-called "habit-forming" qualities of the parent drug.
This situation and its significance perhaps best may be appreciated after a brief review of some of the published opinions on heroin resulting from experience gained in the employment of the drug in medical practice. These have been taken from medical journals of repute in Europe and America and, while they comprise by no means all of the current medical literature of the day dealing with the advantages and disadvantages of heroin, they furnish undoubtedly an accurate picture of the prevailing opinions. As will be seen from the following, while the specific indications for heroin varied according to the opinions of the different writers, it was advocated sooner or later for practically every condition in which morphin or codein had been found useful with the addition of being declared valuable in the treatment of chronic intoxication to these drugs.
Floret,27 1898, after six months' use of the drug in the Poliklinik der Farbenfabriken, states that heroin appeared to be unusually useful, prompt, and dependable in coughs and irritations as well as in pains in the chest and in primary irritations especially of the upper and lower air passages both in acute and chronic form. He states that in dry bronchitis where codein was not effective heroin was and also that it was valuable in the treatment of tuberculosis and asthma. Nothing was said as to its dangers. Floret experimented with the drug at the request of Dreser.
Dreser 28 previously had reported favorably on a pharmacologic and therapeutic study of the drug.
Strube,29 1898, states that his own pharmacologic investigation made on rabbits, dogs, and cats led to the results published by Dreser as to the strength and action of the drug and that following this study he tested it on 50 patients at the Medical University Clinic of Berlin. Most of the material at the clinic were cases of phthisis. He describes the doses employed to produce sleep and relieve the cough and states that the results were satisfactory. He observed no bad effects of any kind but states:

"Patients took the drug willingly and habitues were satisfied with the exchange; many in whose case it was given under proper indication, asked for it again, if it *as replaced by something else or by codein. Whether this gives the first sign of habituation to the drug, I cannot decide with certainty, but this is possible since in patients who took it over a long period, I had to increase the dose gradually and what was obtained at first with 0.005 g. later took 0.01-0.015 per dose and 0.02 per day. It naturally will take further observation to decide, whether on continued use injury to the organism is caused, and whether we shall have a heroinism related to chronic morphine intoxication. So far, I have sought in vain for indication of it in the appearance of the pupils, constipation, etc. From its not inconsiderable narcotic action and the inclination of the patients to use it again, I have deemed it advisable to use it only under strict control and not too freely, so that its good action, which it has under the proper indication, will not fall into discredit through abuse and indolence."

It is noteworthy that in Dreser's 30 announcement to the Congress of German Naturalists and Physicians, 1898, he stated that heroin was ten times as efficacious as codein in lessening frequency of respiration, while only one-tenth as toxic as the latter drug.
In the same year, Manges $1 reported on the use of heroin in coughs, beginning phthisis, and asthma and referred to the treatment by Hirt of Breslau of 35 cases of morphinism of which 27 were cured, and 2 committed suicide during the first three days of withdrawal.
In 1900 in a second report on heroin based on data obtained by correspondence, Manges 32 reviews 341 cases in which the drug was used. He recommends it for many uses and says that habituation has been noted in 6% or 8% "without the bad effects accompanying the morphin habit, none of the patients having suffered from it." 33
On the other hand he states that large numbers of the reports say that the same dose may be used without any habituation. He gives two cases in which it was used in breaking up the "morphin habit" and says it should be tried further for this purpose.

Weiss," 1898-99, advocates the use of heroin without reference to possible dangers.

Harnack,35 1899, states:

"From all that we know so far on heroin in animals and man, I am of the opinion that the delivery of the drug to the profession was precipitate and that a dangerous poison was placed in the hands of unsuspecting physicians, in respect to which not enough can be said in warning."

Turnauer,8° 1899, was delegated by his chief, Dr. Pal, to test out heroin with especial attention to its eventual harmfulness. The maladies treated were phthisis, acute and chronic bronchitis, and dyspnoea of all kinds. He experimented with 48 cases, stating that he noted a tolerance to the drug insofar as the dosage had to be increased in nearly all cases in which the drug was given for a long period. Yet he says as far as he could observe there were "no harmful results, especially as I observed no abstinence symptoms whatever. Generally it appeared that in all cases in which a period of time was allowed to elapse the full effect could again be obtained with small doses." He observed nausea in only two cases. He further states:

"In any event, from this as well as from my observation, it may be concluded that, regarding tolerance to heroin, certain individuals react peculiarly and it is recommended that in the case of old and feeble persons, the initial dose should not be above 0.005."

*    *    *    *    *

"In the above cases, heroin was found to be in general a harmless drug, which in most cases, even in patients accustomed to narcotics, can be used with success for treating coughs and forms in this connection a valuable addition to our therapeutic agents."

Holtkamp,37 1899, Wierzbicki,38 1899, Bougrier,39 1899, Lang," 1899, and Herwirsch,41 1899, all recommended the use of heroin in many conditions and either fail to warn of its dangers or state that it does not lead to tolerance.
Horatio C. Wood, Jr.," 1899, reviews the claims made for peronin, heroin and dionin and welcomes them as substitutes for morphin. He states:
"Of course, it is hardly possible to say as yet whether these remedies are likely to cause drug habits."
He states that it is worthy of note in this connection that both peronine and heroin must be given in ascending doses in order to maintain their effect.
Einhorn," Witthauer ,44 Runke1,45 Kropil," Pollak,47 and Wiesner 48 in 1900 all recommended the use of heroin without referring to any attendant dangers.
Saint Martin," 1900, reported favorably on the drug after conducting experiments on three dogs.
In America in 1900, McGee,5° Fulton,51 Floeckinger,52 Brown and Tompkins," Lowenthal," Daly,55 Lazarus," Hyams," Gifford,58 and Geis 59 all report favorably on this drug after using it for coughs, respiratory diseases, pertussis in children, and as an analgesic and hypnotic. For the most part no mention is made of any dangers consequent upon its use, while Gifford and Brown and Tompkins specifically state that it does not produce addiction.
Joseph Jacobi,6° 1901, after reviewing the experimental and clinical work on heroin, investigates the drug in 85 cases and comes to the conclusion that heroin is superior as a cough soothing drug and should be classed with morphin. He noted that in patients who had never used a strong narcotic drug heroin had a better effect than in those who had used one. This he does not attempt to explain. As to tolerance, he states that if the use of heroin is stopped for several weeks the same doses will be effective as before and that it may be alternated with morphin and codein.
In America, 1901, Martinson,61 Center,62 and Keown," all recommend the use of heroin in therapeutics without mentioning its dangers.
Stewart," 1901, recommends it and states that it is not cumulative and does not tend to produce "habit" but adds: "It should not be put into the hands of patients as it is liable to be overused."
G. W. Wood," 1901, after using it in ten cases states it has no tendency to "habit" formation.
Morel-Lavallee,6° 1902, recommends that in incurable painful maladies it be used in the beginning as it does not cause the euphoria of morphin. Later when from prolonged use its effect is lost, it may be replaced by morphin. He warns against the habit-forming property of heroin in spite of the claims that have been made to the contrary, but thinks it is safer to use than morphin in new cases who have never been accustomed to morphin. Elsewhere it appears that MorelLavallee advised the use of heroin in demorphinisation in certain
selected cases, as Comar and Buvat,67 in commenting on the frequency with which in recent years writers have advised, in the treatment of morphinism, the substitution of some of the derivatives of morphin such as heroin and dionin, criticize Morel-Lavallee's use of heroin even in chronic users of small doses of morphin. They state his teachings have not been followed with the reservations he imposed, but rather have been used indiscriminately, with the result that heroinism all too frequently has been substituted for morphinism. These authors have treated three such cases of heroinism and one of dionism. Duhem 68 also confirms this opinion and states that from then on (1900) the number of heroin users constantly has increased in general practice.
Jarrige," 1902, says, in a review of the work which had been done on heroin, that many articles appearing on heroin have advocated the use of the drug in the treatment of morphinism and he fears that, just as the physician was primarily and principally responsible for the creation of morphinists, he will also become responsible for the formation of heroinists. He calls particular attention to the advertised claims of the virtues of heroin as a substitute for morphin in general therapeusis. He gives the details of the symptoms and treatment of several cases of heroinism, following morphinism or set up in morphinists through treatment by substituting heroin for morphin, stating emphatically that the withdrawal of heroin is accomplished with much more painful and serious symptoms than is that of morphin. He defines heroinism as "the need of heroin," stating that like morphin to the morphinist it is a necessary poison.
The author quotes Morel-Lavallee as follows: "I consider heroin as an admirable medicine from many points of view even if we did not hope through it to some day witness the end of morphinism," and states in contradiction that inquiries made in various institutions where these conditions were treated elicited invariably warnings against the use of heroin in the treatment of morphinism.
In conclusion he states that far from being valuable in the treatment of morphinism heroin only has added another form of narcotism to the already long list.

Pettey,7° 1903, is among the first in America definitely to warn the profession of the dangers of chronic heroin intoxication. He reports that out of his last series of 150 cases of drug habit eight used heroin. In three of these the use of heroin dated from the beginning of their addiction. He states that these cases presented the same difficulty in treatment as do morphin cases.
Montagnini,71 in Italy, 1904, reports a case of heroin habit which he considers of interest inasmuch as heroin had been recommended as the drug that did not possess the dangers of producing "habit" and that could be successfully employed in treating morphinism.
Sollier,72 1905, vigorously attacks the practice of using heroin in the treatment of morphinism or with the idea that the drug does not possess a tendency to tolerance-formation. He states that for several years heroin has been substituted for morphin for the cure of morphinism and that there are now met almost as many heroinists as morphinists. He compares the substitution of heroin with that of cocain in the treatment of opiumism, stating that the latter although essentially false in principle was better justified than the use of the former, as it had to do with chemically different and to some extent antagonistic substances. With heroin, however, no more is accomplished than if the extract of opium were substituted for laudanum or morphin for the latter.
The statements to the effect that heroin is no more toxic than codein, he says, are mistaken as all the heroinists whom he has seen were more profoundly poisoned than were morphinists on equivalent doses. One, he states, is struck at once by their cyanosis, their anaemia, and greater weakness. He states that they are not able to stand the use of the drug as long as are morphinists but deteriorate very rapidly both physically and mentally. He deplores Morel-Lavallee's advice to use heroin as a substitute for morphin in the treatment of morphinism even though only small doses have been used. He states that heroin more than morphin affects the respiration and that in the withdrawal of the drug syncope of respiratory origin is dangerous and difficult to deal with, as the readministration of the drug does not relieve the collapse.

Atwood,73 1905, recalls the claims that heroin is a safe anodyne and hypnotic lacking the objectionable features of opium and morphin. He reports a case of heroin addiction following the surgical use of the drug in a woman who had been cured of her morphin habit years before and warns that, although cases of heroin habit are as yet comparatively rare, they are apt to increase unless more caution is used in administering the drug to neurotic individuals and in coughs, neuralgias, rheumatism, recurring headaches, etc.
In 1906 the Council on Pharmacy and Chemistry of the American Medical Association 74 tentatively accepted, for inclusion in the proposed annual "New and Non-Official Remedies," heroin and heroin hydrochloride giving their therapeutic indications as follows:

"When given in small doses heroin hydrochloride has apparently no effect on any of the vital functions except respiration. . . .
"In large doses it may produce dizziness, nausea and occasionally constipation and in poisonous amounts, twitching of the extremities, great exhaustion and dimness of vision. . . . The habit is readily formed and leads to the most deplorable results."

"On withdrawing the drug from habitues there is said to be a tendency to respiratory failure."

*    *    *    *    *

"Heroin and its hydrochloride are recommended chiefly for the treatment of diseases of the air passages attended with cough, difficult breathing and spasm, much as the different forms of bronchitis, pneumonia, consumption, asthma, whooping cough, laryngitis and certain forms of hay fever. It has also been recommended as an' analgesic, in the place of morphine in various painful affections."

Duhem,75 1907, comments on the increasing number of heroinists seen during recent years and the difficulties in the way of dangerous symptoms which occur in withdrawing this drug. He states that Pouchet pointed out the dangers of heroin when the medical profession was enthusiastically turning to it as a substitute for morphin, which warning, he states, has been well justified.
It has been stated that the widespread use of heroin as a substitute for morphin and as a more stimulating narcotic drug became a matter of general knowledge first in the underworld and that long before the average physician had become aware of the dangers of the drug it was being used freely by certain groups of individuals, especially young men, frequenters of the underworld districts. This is borne out in the report of the health department of Jacksonville, Fla.," when in 1912 the extent of opiate use was investigated. In that year there were 22 heroin users recorded among 343 users or 6.41% of the whole. In 1913 the percentage of heroin users was 5.18% and in 1914 5.27%. In the report of 1914 the statement is made in connection with etiology that heroin is used principally as the result of dissipation and is commonly combined with cocain. The percentage of heroin users as given is incomplete inasmuch as, in the case of individuals who used cocain and an opiate combined, the name of the opiate is not given.
By this time, about 1910, the profession largely had awakened to the dangers of substituting heroin for other opium derivatives and of employing it where any other derivative would be contraindicated. An increasing number of articles pointing out the dangers of heroin administration began to appear in medical literature. Finally the use of heroin declined but its abandonment has been less rapid than was its adoption. Today there is a strong sentiment among the profession that the manufacture of this product could be abandoned entirely not only with benefit to mankind in general but even without serious handicap to drug therapeusis. Other members of the profession, however, claim that heroin in certain conditions has decided advantages over other derivatives of opium.
At the same time, however, common knowledge of the properties of heroin, as well as its significance as a health and social menace, had spread so rapidly through non-medical channels that the opinion of the medical profession as to its safety or danger as a therapeutic agent became a matter of little or no interest.
With the advent of the early state prohibitory laws and later the passage of the Harrison Narcotic Act, the role played by heroin particularly in the underworld became at once apparent. With the enforcement of these laws and the consequent restriction placed on physicians, druggists, and manufacturers of pharmaceutical preparations, an illicit traffic hitherto sporadic became general and apparently well-organized. Heroin particularly was adapted to the purposes of the vendors of illicit drugs, inasmuch as its morphology permitted easily of adulteration with sugar of milk or certain coal-tar products while morphin could be so treated only with difficulty. It was, therefore, the drug of choice in the underworld traffic.
The more recent percentage of heroin users in relation to the total number of opiate users does not indicate the actual role of heroin as an etiologic factor in chronic opium intoxication, inasmuch as the ease with which the drug can be purchased on the streets from peddlers has induced many users of morphin, laudanum, and other opium preparations to change to heroin in order to conceal their condition from official or professional knowledge. Consequently the use of heroin became later not so much a matter of etiologic importance as of current expediency.

In reviewing the very remarkable history of the rapid increase in the use of this drug, its wide popularity as a therapeutic agent, the acclaim with which it was received by the medical profession, and the persistence with which manufacturers advertised its virtues both in technical and lay publications, it is astonishing that physicians were so slow to recognize its dangers and that for the first six or eight years of its employment there were only a few among the large number who proposed its employment in an ever increasing number of conditions, who appreciated the harm that was being done. One wonders why during this period members of the profession, to whom cases of chronic heroin intoxication must have appealed for treatment and who scarcely could be unaware of the growing popularity of the drug among the laity, did not come forward in greater numbers with appropriate warnings. The fact remains, however, that for twelve or fourteen years after its introduction current medical literature included constant references to its value as a therapeutic agent in almost every variety of complaint.

As an influence in the causation and extent of chronic opium intoxication, the illicit traffic in opium and its preparations occupies a much disputed position. If we were to judge by the press notices dealing with alleged confiscations of illicit drugs by federal, state, and municipal officials concerned with law enforcement, we might conclude from the amounts almost daily mentioned in proof of their activities that the importation of opium as recorded in official quarters formed but a small portion of the supply reaching this country. As the amounts confiscated, however, usually are stated in terms of value rather than in pounds or ounces and as these values frequently may refer to the prices asked by peddlers, it is not unlikely that false impressions are made upon the public as to the quantities seized.
As far as we are aware and for reasons which are quite obvious and inherent in the traffic itself, there are no accurate figures in existence. The report of the Committee on Traffic in Narcotic Drugs, appointed by the Secretary of the Treasury, published in June, 1919, states:

"In recent years, especially since the enactment of the Harrison law, the traffic by `underground' channels has increased enormously and at the present time it is believed to be equally as extensive as that carried on in a legitimate manner. This traffic is chiefly in the hands of so-called `dope peddlers,' who obtain their supplies by smuggling from Canada, Mexico, and along the Atlantic and Pacific coasts."

With the sources of information at its command it would seem that this Committee should have had the very best of opportunities to determine accurately the extent of the traffic. The above quoted statement, however, comprises all that the report makes public in this connection and the methods or sources of information which led the Committee to arrive at this conclusion are not mentioned.
There is scarcely a writer who has not referred to the illicit traffic. There is certainly not a law enforcement officer who does not dwell on it. From the statements of individual users from every section of the country with whom we have talked from time to time, there is apparently no place in the United States where these drugs are not available through underground sources of supply if the purchase price is forthcoming. From time to time investigators of other social problems in the course of their studies have uncovered evidence of a widespread traffic in these drugs and have reported the same to our Committee.
That the illicit traffic operates directly to create new users is indicated in the histories obtained by investigators in different sections of the country. There are two motives apparently behind this influence. The peddler seeks by inducing individuals to try these drugs to increase the number of his customers. He supplies a few doses, enough to create a demand for more, and then charges for later supplies. Another not uncommon factor in the creation of new users is found in the activity of certain users, those of the underworld type, who seek to insure their own future supplies by creating a demand for the drug in acquaintances whose financial status is better than their own. Like the peddler they supply these friends with enough of the drug to acquaint them with its "virtues" and then, when a certain degree of dependence has been established, leave them to shift for themselves in anticipation of sharing their supplies in time of need. One or another of these factors repeatedly is encountered in the histories of a certain type of opiate users, more especially of those who use heroin. How widely they have operated and how many new victims thus have been claimed, no one is in a position to state, but apparently such influences have contributed materially to the number of new users of opiate drugs.

One other possible factor contributing to the present extent of the problem has been advanced and has given rise to considerable discussion. Its importance to the reader depends on the conception held as to the actual nature of chronic opium intoxication and the degree to which the field of medicine is involved in the solution of the problem. This factor is comprised in the attitude of the medical profession, first because of tradition, inadequate training or indifference and later because of the operation of prohibitory laws and regulations. That the attitude of the medical profession exerts some influence on the extent of the problem can not be doubted; but there may be difference of opinion as to its importance. The following explains the way in which this factor operates according to those who emphasize its importance:
For the past seventy-five or one hundred years along with the growth of the patent medicine industry there have developed in this and other countries hundreds of "cures" and "treatments" for chronic opium intoxication, ranging all the way from ten or fifteen dollar "home cures" to be used with or without the patients' knowledge, to alleged respectable hospital treatments endorsed by medical men in more or less good professional standing. For the most part, as has been conclusively demonstrated by the United States Bureau of Chemistry working in co-operation with the Post Office Department, by Mr. Adams in his "Great American Fraud" series, by the American Medical Association in its Journal and through its published analyses, as well as by a number of others, the active principle of practically all the home remedies was either a product or derivative of opium in some form or some other powerful drug in dangerous doses such as cocain, chloral, etc. In the great majority of cases, however, these fraudulent cures relied on an opium product, not infrequently the same one that the patient seeking treatment was already taking, such, for example, as morphin. Others preferred to substitute some other opium preparation for the form of drug used by the correspondent. To the morphin user heroin would be sent and to the heroin user morphin. A favorite method of supplying these so-called treatments was in a series of daily doses of such high opium content as to preclude their being safely taken by an intolerant patient. The advertisements of these preparations made the most unwarranted promises and the whole method of procedure from the magazine or newspaper statement which first caught the patient's eye down to the last dose of the last bottle was deliberately fraudulent and without any excuse in rational practice. That thousands of sufferers were duped by the claims of the home remedy "ghouls," as Mr. Adams calls them, is a matter of common knowledge.
In addition to the home remedies there sprang up all over the country private hospitals or sanatoria which through seductive advertisements drew large clienteles. Many of these also were fradulent in character and made no effort to cure their cases, discharging them when their funds were exhausted still suffering from the intoxication from which they sought relief. Others were run by men who were simply ignorant or possibly indifferent and whose therapeutic measures, while not deliberately fraudulent, were so ineffective and left their patients in such a depleted state bath physically and mentally as to make their return to the drug a matter of but a short time, The lack of interest on the part of the medical profession at that time is shown by the fact that the advertisements of many of the latter class of institution were accepted by reputable medical journals; in fact, it is only during comparatively recent years that the Journal of the American Medical Association and others of equal standing have refused to carry advertisements without making preliminary investigations as to the nature of the treatment and the standing of those in charge, Today there are unquestionably a considerable number of institutions where little ar na knowledge of chronic opium intoxication is had but to which through advertisements and correspondence sufferers from this condition are drawn for treatment.
While the enormous growth above referred to of the home remedies and institutions was a direct result of advertising and other publicity, it is very doubtful if they could have obtained the hold on the opium-using public which they did if the regular medical profession, except for relatively few individuals, had nut shown a lack of interest, the natural outgrowth of the generally accepted theories as to the nature of the condition. It is quite natural that, because of tradition and the resulting lack of medical teaching on the subject, the profession as a whole should have been neither interested nor informed.
The result of the aforementioned conditions was, as may be understood readily, the perpetuation of chronic opium intoxication. Patients wandered from one institution to another, bought this remedy and that, applied in vain to their family doctor for suggestions or help, and finally, impoverished, and discouraged, gave up the fight and as best they could continued a miserable existence the reasons for which they could not understand and for which, in many instances, they were not responsible.
The passage of the Harrison Narcotic Act and the adoption of regulations relating thereto have also contributed to the creation of the present attitude of the medical profession. It must be remembered that prior to this time counter sales of these drugs had been the rule in most states and thus the user secured his accustomed amount. With the enforcement of the new law limiting the distribution to one channel physicians were appealed to by hosts of patients who previously had bought directly from the retail druggist or by mail order from the wholesaler. This adjustment was not too difficult, however, and while it somewhat increased the cost to the drug user and added inconvenience it doubtless had a beneficial effect as it brought these cases into the hands of the physician and led to an increase in professional interest that stimulated study and inevitably would have led to many cures and improvements in methods of treatment. The enforcement of the regulations, however, in some cases called into question the judgment and integrity of physicians and druggists and indictments were brought against members of both professions. Whether conviction followed or not mattered little as the effects of press publicity dealing with what were supposedly wilful violations of a beneficent law were most disastrous to those concerned. Such occurrences caused both physicians and druggists everywhere to fear such actions. This attitude may or may not have been justified but it was a very natural outgrowth of the law's administration. At this time, too, were initiated the first public activities directed at relief, through medical investigation and treatment, of large numbers of individuals unable to pay for private treatment—the narcotic clinics which were opened first in Louisiana and California, and later in a number of other states. More than forty such clinics were in operation from time to time. The whole story of their achievements and failures has never been told; they represented a pioneer movement directed at a solution of certain phases of this complex problem. As in all pioneer movements, they underwent a period of experimentation in which mistakes were made but which eventually, according to their proponents, might have led to valuable findings and encouraging results. 'Here again, however, the interpretations and enforcement procedures originating in certain regulations of the Department of Internal Revenue in its administration of the Harrison Narcotic Act resulted in their closing before their development could bear fruit through practical administrative and medical procedures. They were declared illegal, and closed. It is claimed by many of the directors of clinics that their closing directly affected the extent of addiction in the communities in which they were conducted. The opportunity to influence individuals to be treated was lost; incurable cases that were being supervised and kept on a minimal dose of drug reverted to larger doses and lost their positions; drug peddlers returned and exerted, as they had before, their influence in spreading addiction among the younger age groups; petty thieving and pocket-picking and other minor crimes, resorted to by addicts of the underworld in order to secure the means to pay the peddlers' prices, were shown by the police records in a number of communities to have reached their former frequency.
The interest of physicians in these cases thus was checked and they even began to refuse to prescribe. Pharmacists also refused to fill prescriptions and chronic users wandered from one to another and finally were forced in order to secure their drug to seek it wherever it could be gotten—from the peddler at his own price. Thus was an illegal substitute for the legal channels of supply created by the law because the law was so interpreted and administered as to render the registered distributors uncertain of their status.
The illicit traffic thus in part stimulated was not to be satisfied with already existing demand, but sought through initiating new individuals to extend its operations—sound business if otherwise disastrous.

Résumé

At the end of the last chapter, we stated that, although informative and valuable within certain specified limits, the so-called mathematical methods of arriving at an appreciation of the extent of the problem of chronic opium intoxication were not exact. We further pointed out that a review of the influences leading to the present situation as presented by available historic record constituted another and satisfactory method of reaching the same objective. Such a review has been given in the present chapter.
In this chapter examination has been made of the chief influencing factors in the development of the problem from the time of the early unrestricted use and popularity of opium to relieve pain through the periods of ignorance of the dangers of continued use, the discovery of its value for other than therapeutic uses, the influences of such writings as De Quincey's and others of his day, the introduction and widespread use of the hypodermic syringe, the influence of the Civil and other wars, the practice of opium smoking, the influence of the patent medicine industry, the discovery and use of heroin, the illicit traffic, and the prevailing lack of interest in the problem resulting in laxness in medical teachings and practice in the employment of opium preparations. These, in general, were the natural factors leading to the increasingly widespread use of opium in all social groups.

Therefore, regardless entirely of the accuracy of the surveys which give rise to the estimates varying from one hundred thousand to more than a million, the actual number of cases is not of such great importance as are the obvious possibilities for the growth of this problem when its causative factors are considered. These are such as to warrant the best efforts of all groups at prevention, alleviation and control.
It must be realized further that each of the above-named factors is by no means simple and direct in its operation; on the contrary, each one is complex and powerful and includes both direct and indirect elements. They are so interwoven with the fabric of our customs, emotions, and acquired knowledge as to have become an integral part of our civilization. For this reason, their importance must be appreciated with the realization that unless they are attacked in all of their rudiments, their influence will continue unchecked. They present a multitude of problems by no means indicated in the above brief enumeration, each one of which requires for its proper determination intensive study from medical, psychologic, sociologic, and possibly other angles. All too frequently their importance has been overlooked in previous efforts at amelioration and control and for this reason, if for no other, the problem appears to have reached its present magnitude.

To the problem and its solution they are as fundamental as is the nature of the condition itself.
Notwithstanding the fact that for lack of space we have been forced to omit a considerable amount of valuable material and that we have touched upon the earlier history only in the most cursory manper, the evidence of a progressive, widespread growth of chronic opium intoxication is convincing, even though every influence mentioned be accorded but a minimal value as an etiologic factor. If one considers the many influences cited in their relation to deep-rooted human instincts and emotions and the general receptivity of an ignorant public, one must conclude without the aid of statistical data of any kind that chronic opium intoxication affects a large number of our people.

1 Neligan, A. R.—The Opium Question, with special reference to Persia. London, 1927.

2 Thompson, R. Campbell, M. A., F. S. A., Fellow of Merton College, Oxford.

3 The Assyrian Herbal is a translation of the Assyrian Medical Tablets taken from the Royal Library of Ashurbanipal and now a part of a collection in the British Museum.

4 Garrison, Fielding H. An Introduction to the History of Medicine. Philadelphia, 1922.

5 Doringio, Michaele, Breslaviensi, Philoaophiae & Medicinae Doctore. Acroama Medico-Philosophicum de Opii Usu. 1620.

6 Martin, Ernest.—L'Opium, ses Abus, Mangeurs et Fumeurs d'Opium, Morphinomanes. Paris, 1893.

7 Hippocrates, T. VIII, Liv. II, p. 253, Sec. 116. T. VIII, Liv. II, p. 386, Sec. 201.

8 The Seven Books of Paulus Aegineta, translated from the Greek by Francis Adams. London 1844. pp. 279.

9 Theophrastus. De Historia Plantorum. IX. 82.

10 Virgil. Georgics, Lib. I, v. 78—"Lethaeo perfusa papavera somno."

11 Virgil. Aenead, Lib. IV, v. 486—"Spargens humida melle soporiferumque papaver."

12 Macht, D. I.—The history of opium and some of its preparations and alkaloids, Jour. Amer. Med. Assn. Feb. 6, 1915.

13 Jones, John—The Mysteries of opium revealed. London. 1700.

14 Handy, Hast—On opium. Thesis. Philadelphia. 1791.

15 Seaman, Valentine—An inaugural dissertation on opium. Philadelphia. 1792.

16 Smith, W. G,—On opium embracing its history, chemical analysis and use and abuse as a medicine. New York. 1832.

17 Calkins, A.—Opium and the opium appetite-1871.

18 Is it not possible that one aspect of De Quincey's case has been lost sight of by those who so frequently have linked his name with opium? The opium user even of De Quincey's time, as far as we can determine from the literature, did not boast of his affliction and De Quincey's eulogy of the drug and his desire to appropriate to himself credit for an intimate knowledge of its alleged virtues, therefore, do not seem to be characteristic of the opium user. Probably no better example of this attitude of De Quincey, which may of course have been the all too common egotism of the artist, could be found than the following quotation from his Confessions:
"This is the true doctrine of the Church on the subject of opium; of which church I acknowledge myself to be the only member—the alpha and omega."
May not this attitude be rather the psychologic picture of the alcoholic with his very common megalomania? In this connection, it should be remembered that the prepailition used by De Quincey was laudanum which contained 45 per cent. of alcohol, so that at the time that he was taking a pint-8,000 drops—a day he was consuming the equivalent approximately of a pint of whiskey. In addition to this amount of alcohol, as his biographers show, he was a generous partaker of wines and cordials. It is, therefore, not astonishing that the evidence of alcoholism is at least as plain as that of chronic opium poisoning. His was really a case of mixed intoxication and he presented somewhat the picture of the more modern indulger who adds cocain to his hypodermic of morphia or his sniff of heroin. The same characteristics are to be found in certain other writers and statesmen of genius all of whom used an alcoholic preparation of opium.

19 Kane, H. H.—The hypodermic injection of morphine. New York. 1880.

20 Macht, D. I.—The history of intravenous and subcutaneous administration of drugs. J. A. M. A. 1916. Vol. 60. pp. 856-860, in which Macht cites as his authority Bishop Spratt: History of the Royal Society of London. 1667. p. 317.

21 Roubinovitch, J., in Ballet's Traite de Pathologie Mentale. 1903. p. 445.

22 Rynd, F.—Neuralgia: Introduction of Fluid to the Nerve. Dublin Med. Press. March 12, 1845.

23 Macht fails to give the reference to this first publication of Wood's, but gives the following reference to Wood's second publication, evidently the one mentioned by Kane : Wood, Alexander—New Method of Treating Neuralgia by the Direct Application of Opiates to Painful Spots. Edinburgh Med. and Surg. Jour. 1855. Vol. 82. p. 265.

24 Rynd, F.—Dublin Quart. Jour. Med. Sc. 1861. Vol. 32.

25 We have been unable to find Nusbaum's original statement.

26 Allbutt, T. C.—A system of medicine. New York, 1905.

27 Parrish, Joseph—The Probe, January, 1869.

28 Presumably this is Charles Hunter who in a number of articles extols the hypodermic use of morphin, but we have not found any record of a warning written by him.

29 Allbutt, C.—On the Abuse of Hypodermic Injections of Morphia. The Practitioner, 1870, Vol. V, p. 327.

30Calkins, Alonzo.—Opium and the Opium Appetite. Philadelphia, 1871. "Crothers, T. D.—Morphinism and narcomania from other drugs. Philadelphia, 1902.

31McFarland, S. F.—Opium Inebriety and the hypodermic syringe. Trans-New York State Med. Soc., 1877.

32 Kane, H. H.—loc. cit.

33 Roubinovitch—loc. cit.

34 Kane, H. H.—Opium-Smoking in America and China. New York, 1882.

35 Nostrums and Quackery, Articles on the Nostrum Evil and Quackery. Reprinted with additions and modifications from The Journal of the American Medical Association, American Medical Association, Chicago, 1912.

36 Report of Committee on Social Betterment by George M. Kober, M.D., Chairman of Committee. President's Homes Commission, Washington, D. C., 1908.

37 Adams, Samuel Hopkins. The Great American Fraud. Articles on the Nostrum Evil and Quackery. Reprinted from Collier's by American Medical Association, Chicago, 1913.

38 Floret—Klinische Versuche uber die Wirkung and Anwendung des Heroins. Therap. Monatsh, 1898. XII.

39 Dreser, H.—Pharmacologisches uber einige Morphinderivate. Therap. Monatsh. 1898. XII.

40 Strube, G.—Mittheilung uber therapeutische Versuche mit Heroin. Berl. KIM. Wchnschr. 1898. XXXV.

41 Dreyer—Abstract in Jour. Amer. Med. Assn., 1898.

42 Manges, M.—New York Med. J. Nov. 26, 1898.

43 Manges, M.—New York Med. J. Jan. 20, 1900.

44The significance of Manges' statement that heroin leads to habituation but "without the bad effects accompanying the morphine habit" is not quite clear especially when taken in connection with his advocacy of the drug in the treatment of chronic morphin intoxication.

45 Weiss, J.—Heroin, ein neues Substituens des Morphins. Die Heilkunde. 1898-99. Vol. 3. pp. 12-14.

46 Harnack, E.—Veber die Giftigkeit des Heroins. Munch. Med. Wchnschr. July 4, 1899.
47 Turnauer, B.—Ueber Heroins Wirkung. Wien. Med. Presse. 1899. Vol. 40. Holtkamp, A.—Weitere Mittheilungen uber therapeutische Versuche mit Heroin. Deutsche Med. Wchnschr. Apr. 6, 1899.

48 Wierzbicki, S.—Klinische Beobachtungen uber den therapeutisehen Wert des Heroine. Klinische Thera. Wchnschr. July 2, 1899.

49 Bougrier, L.—ttude chimique, physiologique et clinique sur Pheroine. Thesis. 1899.

50 Lang, C. T.—Heroin. Med. Times and Register. 1899. Vol. 37. "Herwirsch, C.—Heroin in Cough. Therap. Gas. 1899.

51 Wood, H. C., Jr.—The newer substitutes for morphine, peronine, dionine, heroin. Merck's Arch. 1899.

52 Einhorn, M.—Phila. Med. Jour. Oct. 28, 1899.

53 Witthauer, K.—Erfahrungen uber heroinum muriaticum. Die Heilkunde. 1899-1900. Vol. 4.

54 Rupkel, J.—Uber die Verwertung des Heroins in der Kinderpraxis. Inaug. Dissertation. 1900.

55 Kropil—Veber die Unschadlichkeit des Heroins. Allg. Med. Central Ztg. 1900. Vol. M.

56 Pollak, J.—Wien. Klin. Wchnschr. Jan. 11 and 18, 1900.

57 Wiesner, J.—Heroin in Surgical Practice. Internat. J. Surg. 1900. XIII.

58 Saint Martin, T.—Etude experimentale des effets de l'administration repetee et prolongee de Tether diacetique de la morphine. Echo. Med. de Lyon. 1900.

59 McGee, J. B.—Heroin in coughs. Cleveland J. M. 1900. Vol. V. " Fulton, H. D.—New York Med. Jour. Dec. 20, 1899.

60 Floeckinger, F. C.—New Orleans Med. and Surg. J. May 1900.

61Brown, S. H. and E. D. Tompkins.—Ther. Gaz. Aug. 15, 1900. "Lowenthal--Heroin in the treatment of phthisical cough and whooping cough. Phila. Med. J. 1900.

62 Daly, J. R. L.—Boston Med. and Surg. Jour. Feb. 22, 1900.

63 Lazarus, B.—A contribution to the therapeutic action of heroin. Boston Med. and Surg. J. 1900.

64 Hyams, B.—Therapeutic studies of heroin hydrochloride. Med. News. 1900. " Gifford, S. L.—Types of cases illustrating the action of heroin hydrochloride. International M. Mag. 1900.

65 Geis, N. P.—Heroin as an analgesic. New York Med. Jour. 1900. "Jacobi, J.—Ueber die Wirkung des Heroins. Wien. Med. Wchnschr. 1901. " Martinson, I. J.—Some experiences with heroin. Med. Times. 1901.

66 Center, C. D.—An inquiry into the action of heroin hydrochloride. Med.

67 Fortnightly. 1901. XIX.

68 Keown, T. W.—Carolina Med. Jour. 1901.

69 Stewart, W. B.—Oklahoma Ivied. Jour. 1901.

70 Wood, G. W.—Cincinnati Lancet-Clinic. Nov. 16, 1901.

71 Morel-Lavallee, A.—Les Alcaloides de l'Opium, Morphine, Heroine, Dionine. Revue de therapeutique. 1902. Vol. 69.

72 Comar, G. and J. B. Buvat—Les Toxicomanes. Presse Med. July 6, 1904.

73 Duhem, P.—L'heroine et les Heroinomanes. Progres. Med. Feb. 23, 1907.

74 Janige, J. L.—Heroinomanie. These de Paris. 1902.

75 Pettey, 0. E.—The heroin habit another curse. Alabama Med. Jour. 1902-3. XV.

76 Montagnini, T.—La Riforma Medica. Aug. 30, 1904.

77 Bonier, P.—Heroine et heroinomanie. Pres** Med. 1905.

78Atwood, C. E.—A case of heroin habit. Med. Rec. June 3, 1905. "Journal Amer. Med. Assn. Oct. 20, 1906.

79 Duhem, P.—loc. cit.

80 Annual Report Board of Health. Jacksonville, Fla. 1912-1913-1914.

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