The opioid epidemic has grown widely in recent years, but it is far from new. It’s been entwined with mankind since the start of civilization.

While the earliest record of opium growth occurred in lower Mesopotamia in 3400 B.C. by the Sumerians who cultivated poppies and isolated opium from their seed capsules, it wasn’t until the years of 460-357 B.C. that Hippocrates, “father of medicine,” realized opium’s usefulness as a narcotic.

In 1806, a German chemist Friedrich Wilhelm Adam Sertürner isolated morphine from opium and it became the linchpin of medical treatment in the 19th Century.

It wasn’t until the Civil War that morphine became widely used as a painkiller. Many soldiers became addicted to the opiate and the post-war addiction they were left with was known as the “soldier’s disease.” The Union Army alone issued 10 million opium pills to its soldiers and 2.8 million opium powders and tinctures, according to the Smithsonian.

In 1856, the hypodermic syringe and hollow needle were introduced in the United States, and morphine began to be used in minor surgical procedures. The use of morphine to treat postoperative and chronic pain marked the beginning of the medicalization of opioids.

In regard to the wide usage of morphine by physicians, David T. Courtwright, author of “Dark Paradise: A History of Opiate Addiction in America” said, “It’s almost as if someone had handed them a magic wand.”

But physicians knew even then that opioids were addictive. Medical journals of the 1870s and 1880s were filled with warnings about the dangers of morphine addiction. Despite this, doctors were slow to stop using opioids as treatments due to a lack of other treatments and limited medical education.

The Smithsonian reported as early as 1895, 1 in 200 Americans were affected by an addiction epidemic which stemmed from morphine and opium powders.

In search of a safer alternative to the abuse associated with morphine, heroin was synthesized in 1898 and was pronounced to be more potent than morphine. It was also proclaimed to be free from abuse liability, the first of several claims like it for novel opiates.

In 1909, Congress passed the Opium Exclusion Act which banned the importation of opium for the purposes of smoking. This act has been considered the beginning of the U.S. “War on Drugs.”

The next important development was in 1924, when the passage of the Heroin Act made illegal the importation, manufacture and possession of heroin. Fourteen years later, the U.S. Food and Drug Administration was given oversight of the safety of drugs, which needed to be proved safe to be sold. Many opioid derivatives such as codeine, morphine and oxycodone were used widely following FDA approval in 1950.

It wasn’t until the 1940s that methadone, a synthetic opiate, entered the scene. A compound structurally unrelated to morphine, methadone contains properties similar to those of morphine, but it is remarkably different. The withdrawal symptoms are less noticeable upon cessation of use with methadone, as opposed to morphine. The onset is slower, lasts longer and less intense for the user.

Clinicians today prescribe methadone to those with substance use disorder as a substitute for morphine; those addicted to methadone can usually be weaned off of it when it is no longer desired by the user. Methadone addicts usually are able to lead more stable, normal lives.

There was a revival of heroin use in the United States in the 1960s, widely attributed to U.S. involvement in the Vietnam — often called the “first pharmacological war.” Drugs were used widely by soldiers throughout the Vietnam war, some sought illegally and others distributed by their commanders. According to a Pentagon study, by 1973, 20 percent of soldiers in Vietnam were habitual heroin users.

By the end of that decade, the World Health Organization (formed in 1948) abandoned the belief that the medical use of morphine led to dependence. This came despite an estimated 35.8 deaths per 10,000 people associated with heroin in 1961.

In 1971, former President Richard Nixon declared the War on Drugs and proclaimed: “America’s public enemy number one in the United States is drug abuse. In order to fight and defeat this enemy, it is necessary to wage a new, all-out offensive.”

Two years later, Nixon created the Drug Enforcement Agency by executive order. America’s number one public enemy regrouped.

Vicodin® (the combination of hydrocodone, an opioid, and acetaminophen, the active ingredient in Tylenol) was introduced in 1978 and became available generically in the 1980s. This is the same decade when opiophobia — a doctor’s fear to prescribe opioids — began in response to the growing demand for pain medication in the United States.

It was in the 1980s that public concern for drug use began to skyrocket, and Ronald Reagan’s Administration only furthered that concern. According to an article by the Drug Policy Alliance, incarceration rates escalated during his presidency, and the number of people behind bars for nonviolent drug offenses went from about 50,000 in 1980 to more than 400,000 in 1997.

A wave of hysteria spread surrounding cocaine usage, particularly that of smokeable, or “crack” cocaine. Meanwhile, powder cocaine was equally potent, but was treated with considerably leaner punishments.

Reagan’s wife Nancy began an anti-drug campaign in 1981, coining the phrase “just say no.” This began a zero-tolerance policy on drugs in the United States, beginning drug education programs such as Drug Abuse Resistance Education (D.A.R.E.) which was adopted nationwide. As a result, clean syringe access and other harm-reduction programs to reduce the rapid spread of HIV/AIDS were blocked.

While former President Bill Clinton initially advocated for treatment instead of incarceration, he soon doubled down on drug policies and would come to reject a U.S. Sentencing Commission’s recommendation to level the disparity between prison sentences for crack and powder cocaine.

By 1984, the Atlantic reported cocaine was used by 4 to 5 million people regularly compared to those regularly using heroin, just 500,000.

It was around this time physicians began to consider narcotics and opioids for the treatment of non-terminally ill patients. Before this, the undertreatment of pain had set up a landscape that would become a catalyst to the clinical prescription of a growing variety of pain medications for all types of pain.

By the 1990s, the market for pain medication with extended release technology — or prescription opioids designed to release the medication over a period of time — had grown tremendously. Examples of this kind of drug are morphine, oxycodone, fentanyl and hydromorphone.

While patient advocates and pain societies sought more information on pain medications, the market for them grew. At the same time, pharmaceutical companies increased their marketing efforts to health care providers.

In 2015, the Atlantic reported an estimated 4 million people, roughly 2 percent of the U.S. population age 12 and up, were using prescription drugs non-medically by 1999. Of those, the report continued, 2.6 million misused pain relievers.

Between the years of 1998 and 2008, the abuse and misuse of products containing hydrocodone and oxycodone doubled, according to the Atlantic, and there were more than 730,000 emergency department visits related to the abuse of prescription painkillers in 2009.

Pharmaceutical companies began to find ways, in the mid-2000s, to formulate pain medications which would be harder to abuse. The FDA approved both extended-release and immediate-release opioids which contained properties meant to deter abuse by the user. Despite researchers’ best efforts, none of the formulas prevented oral abuse.

The Center for Disease Control reported that between 1999-2016, more than 350,000 people died from an overdose involving any opioid, including prescription and illicit opioids.

Opioids killed more than 42,000 people in 2016, according to the CDC, more than any year to date. Forty percent of those deaths involved a prescription opioid.

Because of the continued abuse and misuse of prescription pain medication, the FDA has worked with pharmaceutical companies to manufacture products which contain abuse-deterrent properties and have supported education on proper opioid prescribing.

In the United States, Missouri is the only state not to have implemented a reactive prescription drug monitoring program.