No single person created opioids. The story stretches back more than 5,000 years, from ancient farmers who first harvested opium from poppies to the 20th-century chemists who built increasingly powerful synthetic versions in laboratories. Each step along the way, someone was trying to harness the poppy’s pain-relieving power while escaping its addictive grip. None of them fully succeeded.
The Ancient Origins of Opium
The earliest known reference to opium cultivation dates to around 3,400 B.C. in lower Mesopotamia, in what is now southwest Asia. The Sumerians called the opium poppy “Hul Gil,” meaning “joy plant.” From there, knowledge of the poppy spread through trade routes to the Assyrians, Egyptians, and Greeks. For thousands of years, opium was used in its raw form: the milky sap scraped from scored poppy seed pods, then dried and eaten or dissolved in liquid. It was medicine, ritual substance, and trade commodity all at once.
This raw opium contains dozens of active compounds, but nobody understood that until the early 1800s. For most of human history, people simply knew that the poppy’s sap dulled pain and brought sleep.
Morphine: The First Pure Opioid
The pivotal shift from plant to chemical came through the work of Friedrich Sertürner, a German pharmacist’s apprentice. Between 1803 and 1817, Sertürner isolated morphine crystals from raw opium, becoming the first person to extract a single active compound from any medicinal plant. He tested the substance on rats, stray dogs, and eventually himself, reporting his discovery of a “sleep-inducing molecule” in letters to a German pharmacy journal in 1805 and 1806.
The scientific community largely ignored him at first. So Sertürner kept experimenting, describing the crystallizable properties of his new substance and proving something that overturned a widely held belief: that all medicinal plant compounds were acidic. Morphine was actually a base, a weak alkaline substance. This insight opened the door to an entirely new field of plant chemistry and, eventually, to modern pharmacology. Sertürner named his compound after Morpheus, the Greek god of dreams.
From Morphine to Heroin
Once chemists could isolate morphine, they immediately started tinkering with it. The goal was always the same: keep the painkilling effect, remove the addiction. In 1874, British chemist C.R. Alder Wright chemically altered morphine to create diacetylmorphine, the compound later known as heroin. He hoped it would be a non-addictive alternative. It was not.
Wright’s creation sat mostly unused until 1898, when the German pharmaceutical company Bayer began marketing it under the brand name “Heroin” as a pain reliever and cough suppressant. Bayer sold it over the counter for years before the scope of its addictiveness became impossible to ignore. The company was eventually forced to pull it from worldwide markets.
The Wave of Semi-Synthetic Opioids
The failure of heroin didn’t stop chemists from trying again. In 1916, German scientists Martin Freund and Edmund Speyer synthesized oxycodone from thebaine, another compound found naturally in the poppy plant. Their explicit goal was to create a less addictive painkiller than morphine or heroin. Four years later, in 1920, German chemist Carl Mannich and his colleague Helene Löwenheim synthesized hydrocodone from codeine. Both compounds are classified as semi-synthetic opioids because they start with a natural poppy compound and are then chemically modified in a lab.
These drugs became cornerstones of pain management throughout the 20th century. Hydrocodone received FDA approval in 1943, initially as a cough suppressant. Oxycodone would later become the active ingredient in OxyContin, the drug at the center of the modern opioid crisis.
Fully Synthetic Opioids and Fentanyl
The next leap came when chemists stopped using poppy-derived compounds as a starting point entirely. In 1959, Belgian chemist Paul Janssen synthesized fentanyl, a fully synthetic opioid with no direct chemical link to the poppy plant. Fentanyl is 50 to 100 times more potent than morphine. Janssen designed it as a surgical painkiller for use during operations, where its rapid onset and short duration were advantages.
Fentanyl belongs to a chemical family called phenylpiperidines, structurally distinct from morphine and its derivatives. This matters because it means chemists can create endless variations, called analogs, by making small changes to the molecule. Many of the illicitly manufactured opioids driving overdose deaths today are fentanyl analogs produced in clandestine labs, not derived from poppies at all.
How Scientists Discovered Why Opioids Work
For most of the history of opioid use, nobody understood why these drugs affected the brain so powerfully. That changed in 1973, when researchers Candace Pert and Solomon Snyder demonstrated the existence of opioid receptors in nervous tissue. Their work showed that the brain has dedicated docking sites that opioid molecules latch onto, and that the potency of different opioids closely matches how tightly they bind to these receptors.
This discovery revealed something profound: the human body has its own built-in opioid system. Your brain naturally produces compounds that fit these same receptors, helping regulate pain, mood, and stress. Opioid drugs essentially hijack this system, flooding it with far more stimulation than it was designed to handle. That’s why they’re so effective at killing pain and so difficult to stop using.
Regulation and the Road to OxyContin
The first major U.S. law targeting opioids was the Harrison Narcotic Act of 1914. It required anyone who sold or distributed narcotics, from importers to retail pharmacists to physicians, to register with the government, pay a tax, and keep detailed records of every transaction. Unregistered individuals caught with narcotics faced up to five years in prison. The idea was to make the drug trade transparent and confine it to legitimate medical channels.
For decades, this framework kept prescription opioid use relatively contained. Then, on December 28, 1995, the FDA approved OxyContin, a controlled-release formulation of oxycodone manufactured by Purdue Pharma. The drug was available in 10, 20, and 40 mg tablets designed to release oxycodone slowly over 12 hours. Purdue marketed it aggressively for a wide range of pain conditions, and prescriptions surged. The controlled-release mechanism was supposed to reduce abuse potential, but users quickly discovered that crushing the tablets defeated the slow-release design, delivering a large dose all at once.
The pattern that had repeated since 1874 played out once more: a new formulation promised to solve the addiction problem, and instead made it worse. The difference this time was scale. Millions of prescriptions written through the late 1990s and 2000s created a wave of dependence that, when prescriptions tightened, pushed many people toward heroin and illicitly manufactured fentanyl.
Opiates vs. Opioids
You’ll sometimes see “opiates” and “opioids” used interchangeably, but they’re technically different. Opiates are compounds found naturally in the opium poppy: morphine, codeine, and thebaine. Opioids is the broader term, covering everything that acts on opioid receptors, whether it comes from a poppy, is chemically modified from a poppy compound, or is built entirely from scratch in a lab. In practice, “opioids” has become the standard term for the whole family.