Evidence found in a Sumerian ideogram, depicting the opium poppy as "the plant of joy", suggests that this flowering plant was domesticated for its pharmacologically active milky white juice as long as 8,000 years ago. A papyrus dated 1552 B.C. advises Theban physicians on the use of opium in hundreds of potions for myriad "medicinal" purposes. Arab, Greek, and Roman physicians described opiate toxicity in the 2nd century B.C., and Nero, the Roman emperor, took advantage of this quality of opium by intentionally overdosing Brittanicus in A.D. 55, taking his throne. Egyptian documents describe the use of opium for pain relief, as do the Romans, around this same epoch.

During ancient times, consumption of opiates (a term referring to the alkaloid derivatives of opium) became routine, even commonplace, among many seemingly upstanding citizens, and there is documentation that this occurred without the pathognomonic dose escalation and dysfunction attributed to addiction. Galen, for instance, reported that the political leaders of the day could distinguish the quality of the ingredients of their opiate concoctions, reducing consumption when necessary to execute their duties.

In the 16th century, both German and British physicians commonly prescribed opium admixtures, under the rubric of laudanum, for a variety of ailments. This soon became associated with quackery, since it was purported to be a panacea for all ills at a time when at least some rigor in medicine was being demanded. It was also around this time that there were observations describing tolerance and physical dependence.

By the turn of the next century, two schools of medicine had diverged in France. In the southern regions, physicians preferred "tonics," whereas northern practices influenced by Parisian schools of thought placed great reliance on blood-letting and purging. The former approach was adopted by the English physician, Thomas Sydenham. He, too, used the term laudanum for his alcohol-opium tincture. He wrote, "So necessary an instrument is opium in the hand of a skillful man, that medicine would be a cripple without it."

During the 17th and 18th centuries, physicians and pharmacists throughout England, France, and Germany experimented with a variety of formulations and means of administration in both humans and animals. Physical dependence, manifest by an acute abstinence syndrome, became well known, mostly in those using opiates for what today we would probably classify as mood disorders (anxiety and depressive illness). This era is marked by a substantial increase in the use of psychoactive drugs in Europe for purely experiential purposes.

Concurrently, British commercial interests expanded the opium trade from India to China. This trade became a major revenue generator and offset the trade deficit from Chinese silk, spices, and other commodities. The opium trade had a devastating effect on productivity of Chinese peasants, and in 1799, the Emperor of China issued a proclamation that prohibited importation of opium. This had limited effect, as the market (demand) exceeded the capacity of imperial rule to stop the trade.

In 1805, Friederich Wilhelm Sertürner, an apothecary's assistant in Hanover, Germany, isolated a white crystalline powder from opium that he thought would explain the sleep-inducing quality of the parent compound. He called this purified product morphium, after the Greek god of dreams and sleep, Morpheus. Apparently, he was not a disciplined scientist, and his eccentricities delayed appreciation of his discovery for more than a decade.

The Parisian pharmacist Pierre-Jean Robiquet perfected an extraction process for morphine, and it was soon promoted as both an analgesic and a cure for opium addiction. Commercial morphine appeared in London in 1821, and wholesale production by the German pharmacist, Heinrich Emanuel Merck, began a few years later.

With the development of the hypodermic syringe in the mid-19th century, morphine could be injected directly into painful areas (called neuralgias), with the thought that this would induce a localized anesthesia. In Victorian times, neuralgias were attributed to both sexual repression and over-indulgence. Ironically, the inventor of the hypodermic syringe, Dr. Alexander Wood, an Edinburgh physician, was convinced that injection of morphine, in contrast to oral ingestion, would obviate the growing problem of morphine addiction.

Diacetylmorphine was synthesized during the latter part of the 19th century by the English chemist, C.R. Alder Wright, and it was soon found to be effective for the relief of respiratory symptoms by Heinrich Dreser, chief pharmacologist for the German pharmaceutical company, Bayer. Bayer marketed this synthetic opioid (a term referring generically to alkaloids, their synthetic derivatives, and physiological substances with similar effects) as a cough suppressant under the trade name "Heroin." It was introduced to British physicians in a Lancet report, which stated that heroin is not habit forming. The assumption that heroin might be useful to wean morphine "habitués", of course, proved to be disastrous, and was compounded at the turn of the 20th century, when legislation proscribing opium smoking led to an increase use of heroin by intravenous injection.

Early in the 20th century, growing use and abuse of opioids and other drugs in the United States led to increasing public concern, and reaction by politicians. In 1906, the Pure Food and Drug Act was passed, which gave the government the obligation of regulating drugs and establishing their safety and efficacy before entry into the U.S. market. This was followed in 1914 by the far-reaching Harrison Narcotics Act, which applied controls to opioid drugs and, among other features, prohibited physicians from prescribing opioid drugs to addicts. In 1919, the Supreme Court upheld this law (Webb et al versus the United States) and stated that a physician must not provide opioids for the purpose of maintaining an addict. Dispensing centers for maintenance were closed, driving procurement underground. Addicts who obtained drugs illegally became criminals, and drug use was increasingly viewed as being under the purview of the criminal justice system, rather than the health care system. In 1937, the Marijuana Tax Act outlawed cannabis and heroin, adding further aspects of drug use to the criminal code.

Throughout the 20th century, efforts to stem abuse and addiction through law and regulation surged in the United States. In 1970, the Federal Controlled Substances Act increased the monitoring of the manufacture, prescribing and dispensing of opioids and other controlled drugs. It required registration of all prescribers of controlled drugs, and categorized potentially abusable drugs into five schedules, each with different regulatory mandates. The law stipulated that drugs in Schedule II, such as morphine, could not be prescribed by telelphone, nor could they be refilled without a new written presciption. These federal efforts were mirrored at the state level, where a complex array of laws and regulations created further requirements for prescribers and patients, and an additional set of civil and criminal penalties that could be applied to those prosecuted.

This societal decision to regulate medical practice and criminalize the administration of opioid drugs in some contexts led to secondary phenomena, with effects of their own. Prescribers became increasingly concerned about the potential for investigation and sanction or prosecution. To some degree, this concern has contributed to the underuse of opioid drugs. Equally important, the criminalization of opioid addiction fostered an illicit drug trade that, in turn, brought new problems, including the involvement of organized crime and violent gangs in drug trafficking. Over time, all these problems--the undertreatment of pain, the occurrence of opioid abuse and addiction, and the criminal activities surrounding opioid trafficking--have increasingly undermined the public health. Clearly, pursuant to pain management and opioid analgesia, there is a pressing need for rational and consistant policies, initial and continuing education of healthcare professionals, and application of sound principles of assessment, prescribing, and management.

Read more. Fine P, Portenoy RK: Opioid analgesia. New York: McGraw Hill, 2004. Download Chapt 1

The intent of this book is to help clinicians make practical sense of the varied and often conflicting issues (pharmacological, clinical, and regulatory) surrounding opioid pharmacotherapy, in order to promote the most healthful outcomes possible for patients in pain. The aim is to improve knowledge and skills related to both the principles of prescribing and the management of risk. In this way, healthcare professionals and those they serve may benefit increasingly from the unique therapeutic potential of this drug class, and fear less the undeniable, yet manageable, potential for harm.