Was heroin originally developed as a cure for morphine addiction?

Question

The video What Does Heroin Do To Your Body? claims that heroin was originally developed by the Bayer pharmaceutical company as a treatment for tuberculosis and morphine addiction. Is this true?

Answer 1

No, absolutely not! Heroin was not 'developed as a morphine addiction cure.'

One can say that it was trademarked by Bayer and then tested and marketed as a safe alternative for morphine or codeine, in respiratory illnesses. But when it came to market, there was not a shred of a hint pointing towards Heroin being anything like a cure for morphinism. Whether that is an urban legend or just a lie or myth,^* it is untrue to claim that Bayer developed Heroin as a cure for morphine addiction.

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That statement is wrong on many levels.

First, Heroin is just the trademark name for the molecule diacetylmorphine or diamorphine.

This substance was discovered already in 1873/74 by an English scientist called Charles Romley Alder Wright. This discovery of diamorphine was more or less 'systematically accidental' as he was trying to uncover the chemical structure of morphine, synthesising a lot more substances in that family tree by just mixing various alkaloids and strong reagents.

Wright did not concern himself overmuch with the use made of his new creations. For him, this was an exercise in chemical mapping, rather than practical medicine. After exhausting codeine and morphine, he moved on to the chemistry of Japanese camphor, and then to household soaps and fireworks. Nonetheless, some of his substances were tested on animals, in London and later in Edinburgh. The investigators concluded that none of Wright’s morphine compounds had any significant advantage over morphine itself.

— Tom Carnwath & Ian Smith: "Heroin Century", Routledge: London, New York, 2002, p15–16.

When then in the late 1890s Bayer 's Dreser, Eichengrün and Hoffmann took up these breadcrumbs left behind, they formed a theory that acetylisation of natural compounds would reduce generally their side effect profile, as we also see indeed from aspirin and earlier in Tannigen.

But at first their sole desire was to find a marketable and profitable product. As such they saw that respiratory diseases were one of the leading causes of death, mainly tuberculosis.

They called the resulting compound Tannigen. It was less bitter than tannic acid and was also more effective. It quickly became popular among doctors and patients.

Encouraged by his success, Dreser set up a research group to investigate the acetylation of other medicines. The leaders in this group were Felix Hoffman and Arthur Eichengrun. In August 1897 they acetylated salicylic acid, producing the compound which was later called aspirin. Just a fortnight later they acetylated morphine and produced diamorphine, later called heroin. Within the space of two weeks they had created two new substances of astounding importance. Both could be leading contenders for the title of most important drug of the twentieth century.

Of the two new compounds, heroin progressed most easily. Dreser was soon convinced of its power as a treatment for tuberculosis. He developed it quickly through animal and human testing, and brought it to the market in 1898. He thought it had a specific stimulatory effect on respiration, similar to that of digitalis on the heart, and he named it heroin in reference to the contemporary fashion for ‘heroic’ treatment, that is to say treatment that used powerful medicines in high doses.

Carnwath & Smith, p18.

At no point up to this are the habit-forming issues with opiates discussed in any great detail.

The English Wright testing was abandoned after it was found to be both ineffective and quickly approaching danger levels:

[…] great prostration, fear and sleepiness following the administration, with the eyes being sensitive and pupils dilated, considerable salivation being produced in the dogs, and slight tendency to vomiting in some cases, but not actual emesis. Respiration was at first quickened, but subsequently reduced, and the heart's action was diminished and rendered irregular. Marked want of coordinating power of the muscular movements and the loss of power in the pelvis and hind limbs, together with a diminution of temperature in the rectum of about four degrees, were the most noticeable effects.

— C.R.A. Wright: "On the Action of Organic Acids and Their Anhydrides on the Natural Alkaloids." Journal of the Chemical Society. (12) July 1874. p1031.

The German testing took place with the workers at Elberfeld, with pills, powders, drops and injections administered to ease their widespread TB suffering. This proved very successful and Dreser went on to publish articles in journals:

— Heinrich Dreser (Elberfeld): "Pharmakologisches über einige Morphinderivate", Therapeutische Monatshefte 1898, Vol 12, Nr.9, p509–511 (archive.org) The directly following article by Floret describes the human experimentation on Elberfeld workers…: 'very well tolerated, enables more working, no sign of habituation'
—— "Über die Wirkung einiger Morphinderivate auf die Atmung", Pflügers Archiv für die gesamte Physiologie, 1898, Bd. 72.
—— "Bemerkungen zu dem Aufsatz Prof. Harrnack's über die Giftigkeit des Heroins", Münschner medizinische Wochenschrift, 1899, Nr. 30. (archive.org)

In the first publication he exclusively compares morphine and codeine to diamorphine concluding that diamorphine is much more effective and offering a larger therapeutic window, from which he concludes that it is indeed much safer to use to suppress coughs and easing breathing. He acknowledges that some rabbits he experimented on died from overdose of respiratory arrest, but has zero mentioning of any form about 'habit' (forming), addiction, not even the now well known tendency for increasing dosage over time for the same effect (pharmacological habituation).

One reason to overlook these possible dangers from addiction is found in the fact that rarely any human subject reported any kind of euphoria, as the injected doses were chosen indeed as low as possible, and furthermore, the main route of application was as drops via the oral route. This mode of administration is far less likely to induce the rush the dope fiends desired.

The 1899 Dreser article is a response to an early and harsh criticism about the naiveté the early tests were done at Bayer by Dreser and Floret. The critique Harnack warns that the toxic effects of diamorphine are not to be overlooked as mere animal experiments are well and good but not sufficient, and that any pharmaceutical needs more long term studies in humans to be declared 'safe & well tested'. Harnack clearly warns also that since the substance had already found its way into layman circles (mountaineers combating altitude sickness and breathing problems in great heights as a somewhat counterintuitive actual example), it would stand to reason that diamorphine might also cause morphinism to be developed, or well in this case: heroinism.

In the early years there was just no talk at all about the idea to use heroin as a substitute for morphium. The selling strategy was on coughs alone:

Or as Wikipedia describes it:

Heroin was initially invented and marketed as a sedative for coughs with little side effects.

Until roughly eight years after its market introduction, when the habit-forming properties became slowly known as well, experimenting doctors came to the idea and then Bayer officially embraced it, that heroin might not only be sold as medicine for pain and respiratory illnesses, but also as a morphinism substitute — for weaning and curing that.

In America it was Squibb's Materia Medica of 1906 which first listed it officially as a cure for 'morphinomania':

When exactly this seemingly widespread trend indeed started, to have doctors experiment on live subjects trying to treat morphinism with heroin as sometimes 'enthusiastic whispers' or just 'talk', seems difficult to pinpoint. But one of the earliest mentions for Heroin as a recommended substitute in a scientific journal is from 1900/01:

Morel-Lavallée empfiehlt wann das Heroin als Analgeticum an Stelle des Morphiums. Gerade weil das Heroin die Schmerzen nicht so unmittelbar beseitigt wie das Morphium und keine Euphorie im Uebrigen hervorruft, ist die Gefahr des chronischen Abusus nicht vorhanden Andererseits ist nach Verf. auch bei leichteren Morphinisten das Heroin das beste Ersatzmittel für das Morphium. Er giebt sofort statt des Morphiums nur Heroin und zwar in sechs­ fach kleinerer Dosis. Ueber die hierbei doch nicht ausbleibenden Schwierigkeiten muss das Original verglichen werden. (Hev. de méd., 1900.)

— Monatsschrift Psychiatrie und Neurologie 1901;9:159 DOI: 10.1159/000221398

This apocryphal knowledge spread only in reverse:

In the early 1910s morphine addicts "discovered" the euphorising properties of heroin and this effect was enhanced by intravenous administration. Heroin became a narcotic drug and its abuse began to spread quickly.

— S Hosztafi: "[The history of heroin]", Acta Pharm Hung, 2001 Aug;71(2):233-42. PMID: 11862675

A nice and accessible overview is here. Less accessible, but to the point, for the development phase the motivations were:

Dreser began his research on diacetylmorphine in rabbits, but soon moved on to human beings; his main concern was to assess its value as a substitute for codeine in severe coughing. […]

The papers by Dreser reveal that studies in rabbits had convinced him that diacetylmorphine, in addition to relieving cough, was uniquely able to both slow and deepen respiration. Investigations on volunteers and patients seemed to confirm this finding and led Dreser to conclude that the new drug would be of immense value in severe respiratory disease since it is not only suppressed cough but could even assist in clearing the lungs of excess phlegm and other matter. Convinced that the value of the new drug lay in its combination of cough-suppressant activity with a stimulant action on the respiratory system, Bayer registered the name heroin in June, 1898. Higby described how the company’s belief that it had a highly specific stimulant action on the lung was enthusiastically confirmed by many physicians. A parallel was even drawn between the action of digitalis on the heart and heroin on the lung, both being judged to be drugs with a highly specific action of slowing the activity of their target organ while increasing its strength.

When heroin was launched in September, 1898, Farbenfabriken vorm. Friedrich Bayer & Co made no attempt to suggest that it had any clinical role other than to afford relief in respiratory disease. An early clinical survey in the USA concluded that heroin was inferior to morphine as an analgesic, a view reflected in the monograph on acetomorphine (the original approved name for heroin) in the British Pharmaceutical Codex of 1907:

“Acetomorphine resembles morphine in its action in allaying peripheral irritation and relieving pain. The introduction of acid (or alkyl) groups into the morphine molecule, however, weakens, though it does not remove, its depressing action on the respiratory centre, and lessens its narcotic effect. Acetomorphine thus resembles codeine, and is much employed to relieve irritable cough, especially in phthisis, asthma and bronchitis with dyspnoea. Its use is not followed by headache, and it does not usually constipate. Glycerinum Acetomorphinae and Elixir Acetomorphinae Compositum are valuable preparations to allay cough, the latter combining with acetomorphine the expectorant properties of terpin hydrate.”

This extract shows that the claim of a stimulant action on the respiratory centre had by then been dismissed, but it was not until 1911 that von Issekutz published evidence to show that Dreser had been mistaken. Heroin actually had depressive effects on the respiratory system and so its action was qualitatively similar to that of morphine, codeine, and ethylmorphine. The monograph in the British Pharmaceutical Codex which appeared that same year added a cautionary phrase before its reference to the treatment of irritable cough:

“acetomorphine resembles codeine, over which it is very doubtful if it possesses any advantage: it is much employed to relieve irritable cough especially in phthisis, asthma and bronchitis, with dyspnoea”.

After nearly 12 years of use, the clinical rationale for the introduction of heroin was being challenged.

Since heroin is about twice as potent a cough suppressant as morphine, the small oral doses required for cough suppression would probably have produced habituation in only a few patients when it was first introduced. Higby argued that since heroin was mainly administered in cases of chronic lung disease, medication would have been continued, thereby hiding withdrawal symptoms. Thus, for a time heroin acquired the reputation of being no more addictive than codeine.

However, the 1911 edition of the British Pharmaceutical Codex observed that it was nearly as easy to become addicted to the habit of taking acetomorphine as morphine.

The question of addiction became a matter of widespread public concern in the USA after the publication, in 1912, of a report by Phillips, a physician who cited cases of heroin addiction among people who sniffed the drug in a similar manner to that of cocaine. Addicts had exploited the absence of any legislation to restrict the sale of the supposedly non-addictive heroin.

— Walter Sneader: "The discovery of heroin", The Lancet, Department of Medical History, Volume 352, Issue 9141, p1697–1699, November 21, 1998. doi

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* A seemingly straightforward and direct answer to the question appears in this passage:

Some of the myths about it concern the work of Dreser and Floret. Even the authoritative tome The Opium Problem, published in 1928 by Dr. Charles Terry and Mildred Pellens, dealt with the discovery of heroin as a “most unfortunate influence” and observed, in a misleading passage,

“Dreser in Germany in 1898 produced heroin … 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.”

Such half-truths were repeated and increasingly distorted over the years; a typical version presented in 1974 in an otherwise sound book by John B. Williams, Narcotics and Drug Dependence, claimed:

“Heroin was first produced commercially in Germany in 1898 by Dreser as a cure for morphinism.”

But as we have seen, Dreser and Floret viewed heroin as cough, chest, and lung medicine. While they believed it to be nonaddictive, in this report neither doctor advocated the use of heroin in the treatment of morphine addiction. Nevertheless, the mythological explanation of heroin’s birth is widely accepted even today by leading academicians and drug-abuse officials. Dr. John C. Kramer, of the Department of Medical Pharmacology and Therapeutics, University of California at Irvine, was sufficiently intrigued by the persistence of this myth to conduct an investigation of it. He reported in 1977 that

“between 1899 and 1902, four physicians, a German [not Dreser], two Frenchmen, and an American, wrote papers advocating the use ofheroin as an aid in withdrawal from morphine addiction.”

But even these four physicians were quite cautious about the use of heroin in addiction treatment and generally did not advocate long-term maintenance with the drug. Dr. Kramer wondered, as have I, about how the myth started. His answer:

In the years following 1910, Hamilton Wright [a prominent physician, anti narcotic crusader, and statesman] and others sought to push the nation and Congress to support narcotic control legislation. In part they did this by exaggerating certain data and distorting reports regarding addiction. Among the myths they created was the depiction of all opiates as the “Demon Flower.”…
In particular, heroin was painted as a special evil. The frequency of its use as a substitute in withdrawal was exaggerated far out of proportion to the facts and the statement that it had been first introduced for this purpose was totally false. Not only was the tale used as a means to demonize heroin but it also offered an opportunity to unfairly depict physicians as important contributors to the drug problem.
Evidently, the story was not contradicted at the time and thus became part of popular belief. Repeated in print over the years, even authorities in the field have come to accept it as valid. The bad press that heroin received during the late teens and the twenties was unjustified.

Kramer emphasized that the story that heroin was “introduced … as a substitute in the treatment of morphine addiction” was a “totally erroneous belief.” It would seem, nevertheless, that the medical world must have been waiting for a new narcotic drug for the treatment of organic illnesses—one that might be nonaddictive.

— Arnold S Trebach: "The Heroin solution", Yale University Press: New Haven, 1982. (archive.org, p40–41.)

Answer 2

The claim from the video:

The claim seems to mostly true, if you look at what Bayer intended to produce rather than what they did produce.

Bayer wanted a process to make codeine, which was used to treat respiratory diseases and as a less addictive alternative to morphine. The idea was to prevent morphine addiction rather than to cure it.

Long version:

According to Wikipedia, Bayer wanted to produce codeine, a derivative of morphine that was already known at the time. The folks doing the work came up with a process that made what became known as heroin — their process that was intended to replicate codeine instead produced a new derivative.

Bayer wanted to make codeine because it wasn't as potent or as addictive as morphine.

Heroin turned out to be more potent than morphine, and more addictive as well.

They knew it was more potent right from the start, and may (or may not) have known it was more addictive.

In any case, it was at first marketed as a less addictive alternative to morphine.

Codeine was at the time used in the treatment of respiratory diseases — that includes tuberculosis.

Codeine was used because it suppresses coughing. It didn't do anything to cure the disease itself, but it made the patients more comfortable by relieving the coughing.

The intent was therefore clearly to treat respiratory diseases (pain relief for tuberculosis patients) and reduce the number of patients who became addicts when using morphine.

Heroin was indeed used to treat respiratory diseases, but it greatly missed the mark on being less addictive.

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Bonus:

The video claims that heroin was first produced in 1898. Wikipedia says it was first produced in 1874 in England, but nothing was done with it then outside of some animal experiments.