Synthetic opioids: a historical and clinical review

Opioids are a class of drugs including fentanyl, heroin, oxycodone, and more.

Morphine, heroin, codeine, and more were derived from opium

Opium reached the US at about the time early colonists were itching for ways to soothe aches and pains. The active ingredient in the substance was isolated in the early 19th century, eventually leading to the manufacture and commercial sale of morphine, heroin, and other opium-based drugs.

Opium is a milky liquid substance extracted from unripe poppy plant seeds

It's been used for ages to reduce pain and induce euphoria, both of which are side effects of the plant's alkaloids—nitrogen-based compounds with pronounced physical effects. Isolating and synthesizing derivatives of these naturally occurring chemicals enabled the invention of morphine, heroin, and other opioids.

Opium's history traces from religious use to mass-market commercial products

Religious or medical use of opium was present across Europe and Asia as early as 5000 BCE. By the 16th century, humanity had come to see opium as more than medicine: It was a marketable product. This perspective also defines today's relationship with opioids, highly addictive painkillers at the heart of an ongoing drug crisis.

Evidence of opium use dates to as early as 5000 BCE

Archaeological evidence shows the use of the poppy plant for its pain-killing properties likely originated in the Mediterranean before making its way to the East and West via trade. It has since inspired two eponymous wars, and highly addictive derivatives of the naturally occurring substance have led to an ongoing overdose crisis.

From prescriptions to street drugs: Opioids trajectory across America

Exclusive data obtained by The Washington Post from the Centers for Disease Control and Prevention shows how individual counties moved through three waves of the opioid crisis, each wave paving the way for the next. Between 2011 and 2017, the drug responsible for the majority of overdose deaths shifted from prescription pills to heroin to fentanyl. Together, oxycodone, hydrocodone, heroin, and fentanyl have been major drivers in declining life expectancy in the US.

The three waves of the opioid crisis: overprescription, heroin, and fentanyl

The US opioid crisis has unfurled in three distinct waves, each spiraling into an epidemic that's killed millions. The first crested in the 1990s with the overprescription of opioids for pain relief. The second manifested as heroin overdoses in the 2010s. The third began in 2013 with the rise of deaths related to tramadol and fentanyl.

Opioid prescription rates by states and counties

The origins of the US' ongoing opioid crisis are typically traced to the more than 1 billion prescription pain pills that flooded medicine cabinets between 2005 and 2019. This prescription opioid epidemic resulted in more than 210,000 fatal overdoses and set the stage for the ongoing crisis fueled by heroin and fentanyl.

Why is fentanyl poisoning street drugs?

A few grains of fentanyl, a synthetic opioid far more potent than heroin or morphine, is enough to kill a typical adult human. It's made its way into other, less lethal street drugs, where it may be used to increase the highs experienced by unknowing users, increasing their likelihood of addiction and overdose. This 39-minute podcast episode is the first half of a two-part series exploring fentanyl's rise.

The story of the Sackler empire behind highly addictive OxyContin

This investigative report examines how the Sackler family built its fortune through Purdue Pharma’s aggressive marketing of OxyContin, a highly addictive painkiller. Through 2017, the drug had generated more than $30B in sales for Purdue Pharma, controlled by the Sacklers.

Why are drug dealers putting fentanyl in everything?

A few grains of fentanyl, a synthetic opioid far more potent than heroin or morphine, are enough to kill a typical adult human. It's made its way into other, less lethal street drugs, where it may be used to increase the highs experienced by unknowing users, increasing their likelihood of addiction and overdose.

Overuse of opioids can lead to hypersensitivity to pain.

One person dies from opioids every 7 to 8 minutes

This collection of infographics by the National Institute for Health Care Management helps put the crisis into perspective. The opioid epidemic has had three waves. Opioid-related deaths increasingly involve synthetic versions of the drug class, contributing to 83 percent of all opioid-related deaths in 2020. Use these infographics to learn more about the crisis.

Opioids mimic naturally produced endorphins to dull pain.

Fast, cheap, and deadly: How fentanyl replaced heroin and hooked America

This interactive article details how fentanyl has largely replaced heroin in the drug trade, with fatal results. Fentanyl was first developed in 1959 as an anesthetic for pain relief, but the drug took hold in the US black market in 2014 and has since exploded in the intervening decade.

The Cincinnati Enquirer's Pulitzer-winning look at the opioid epidemic

Synthetic opioids kill someone in the US every 16 minutes. Communities across the country have been ravaged by deaths, overdoses, jail time, and babies born with drug-related medical problems as opioid abuse became a typical feature of many American towns. This seven-part exposé provides an inside look at the effect in southern Ohio and northern Kentucky.

Learn about the US opioid crisis in this free course

Where did the US opioid crisis come from, and how did it spread? Learn this and more in this free, online Harvard University course. Learn about the disease model of addiction treatment and management, and get up-to-date with public health and law enforcement's current harm reduction practices. This free resource gives users a greater understanding of opioid addiction and the epidemic still haunting the US.

Why the human brain loves opioids

When opioids enter the brain, they dock in receptors, blocking electrical pulses such as those that communicate pain. They also trigger the release of dopamine, a neurotransmitter tied to motivation and associated with stress relief.

Fentanyl can be up to 100 times more potent than morphine

A synthetic opioid, fentanyl is highly addictive and incredibly fast-acting—a fatal dose is equal to a few grains of table salt. Once it enters the body, fentanyl floods naturally occurring opioid receptors, which can cause the body to shut down its breathing reflex, leading to a fatal overdose.

Opioid epidemic 101: lawsuits and settlements

State and local governments trying to address the opioid epidemic have sued organizations they believe started and supported the crisis. Companies that made, distributed, or contributed to sales of the highly addictive painkillers are expected to pay more than $50B in settlements. These settlements specifically state that at least 85% of settlement funds must be spent on addressing the epidemic, though where exactly the money is going is unclear.

Drugs 101: An interactive guide

What's the difference between opioids and psychedelics? This guide details specific drugs and their various associated effects. Drugs in this wheel fall into seven categories: stimulants, depressants, empathogens, psychedelics, dissociatives, cannabinoids, and opioids.

See how DOJ prosecutors took down a pharmaceutical company's executives over the opioid crisis

This FRONTLINE documentary follows federal prosecutors as they used anti-racketeering laws to convict executives at Insys Therapeutics, a pharmaceutical company that bribed doctors to overprescribe a fentanyl painkiller.

Methadone binds to the same receptors as heroin and other opioids

Methadone is a long-acting opioid agonist that works by binding to the same brain receptors as other opioids (like heroin or morphine), but without producing intense euphoria. It reduces withdrawal symptoms and cravings, helping people stabilize and avoid illicit opioid use.

The story of Marie Nyswander, the woman who co-discovered methadone maintenance

Methadone, an opioid with distinct effects from heroin, revolutionized heroin addiction in the 1960s. Marie Nyswander was a psychoanalyst who helped discover the treatment process which is still in use today. Here's a podcast episode examining her life and role in the field of addiction treatment.

The body produces its own opioids that act on several receptor types throughout the body, triggering the release of dopamine and suppression of noradrenaline, neurotransmitters associated with reward and alertness, respectively.

A workplace back injury and the opioid prescription that followed set one Texas father on the path the Washington Post's video profile calls his rise to fentanyl 'kingpin.'

Aspirin was the first synthesized anti-inflammatory drug

Once used by the ancient Sumarians—extracted from willow bark—but now synthesized in the lab, the active ingredient of this popular medication has been used to treat headaches and pain for thousands of years.

Narcan is an opioid antagonist that can rapidly reverse overdoses

Naloxone, also known by the brand name Narcan, is an opioid-overdose reversal medication that typically begins working within a few minutes. An opioid antagonist, the treatment attaches to opioid receptors without activating them, forcing opioid molecules out of their respective receptors and allowing users' breathing rates to normalize.

How Western psychedelics research fell to the wayside

Psychedelics' modern era began when LSD was discovered in the 1930s. By the 1950s, clinical trials were underway. US user experimentation outside of medical settings (and high-profile violence, like the Manson murders) inspired negative attitudes toward psychedelics, leading to use restrictions that prohibited companies from patenting psychedelic compounds. This strangled psychedelics' profitability until the 1990s when the government loosened its grip and psychedelics research began seeing a resurgence.

The pharmaceutical industry evolved, in part, from the discovery of synthetic dyes

In 1856, a chemist accidentally discovered mauveine, the world's first synthetic dye, while trying to make quinine to treat malaria. The synthetic dyes that followed helped reveal germs under microscopes, paving the way for modern imaging techniques and breakthrough treatments, such as antibiotics.

Fentanyl is better at crossing the blood-brain barrier than other opioids

Among opioids, fentanyl is uniquely adept at crossing the blood-brain barrier—the brain's security fence against harmful substances. This enables a lightning-fast high. It ends just as quickly, sometimes within minutes (where a heroin high lasts hours), and still results in the same withdrawal symptoms.

LSD (better known as acid) was created in 1938 by Swiss chemist Dr. Albert Hofmann

Lysergic acid diethylamide, better known as LSD or acid, was first developed synthetically in 1938 by Swiss chemist Dr. Albert Hofmann. It's since become a linchpin for an entire aesthetic, fueled a counterculture movement, and is being studied for potential therapeutic uses.

Addictive drugs can cause dopamine levels to become ten times higher than normal.

Psychoactive drugs found in 1,000-year-old bag made of fox noses

Archaeologists in Bolivia have uncovered an ancient bag filled with "amazing goodies" that suggests the owner or owners were well-versed in the properties of psychoactive substances and sourced goods from well-established trade routes. This article details the findings, which shed light on how ancient peoples in the region consumed and obtained psychoactive substances.

Psychedelics are being fast-tracked for research after a 2026 executive order

Many such compounds (including LSD, psilocybin, and more) are classified as Schedule I drugs—illegal to possess and federally regarded as having no medical use. Researchers say such restrictions have created significant hurdles for formal clinical trials. With this executive order, the FDA will enable work particularly focused on depression, PTSD, and alcohol use disorder.

LSD fueled a countercultural movement before evolving into a potential therapeutic

As the use of recreational psychedelics became common, authorities were quick to claim LSD had lasting adverse effects, criminalizing the drug and halting scientific study for decades. Over time, LSD's reputation shifted from a potential source of enlightenment to a dangerous drug that could dim a person's future, and back to a possible therapeutic compound.

Doctors ignored women's pain as a nurse replaced their fentanyl with saline

This five-part podcast series, produced by Serial Productions, focuses on the experiences of women undergoing fertility treatments at a Yale clinic where a nurse secretly replaced pain medication with saline solution. This led to women experiencing excruciating pain during procedures, but the clinic downplayed or ignored their complaints.

See how antidepressants—used by roughly 1 in 10 Americans—were discovered.

How the Myanmar coup fueled a rise in illegal drugs

According to the UN, Myanmar remains the world’s second-largest producer of heroin. Inside Myanmar, almost all the drugs come from one place: Shan state in the Golden Triangle region, south of China, where Myanmar meets Thailand and Laos. The...

Visualize the global supply chain of medicine, which may begin with basic research in the US, but outsource intermediate steps.

An eye-opening interactive journey into the global drug trade

POPPY Interactive reveals how drug money destabilizes entire countries, fuels global conflicts, and allows a worldwide illegal economy to grow. Navigating the site involves diving into three major routes—the Northern Route, the Balkan Route, and...

Naltrexone blocks the reward effects of alcohol and opioids

Naltrexone is used to treat alcohol and opioid dependence, blocking opioid receptors in the brain, reducing cravings, and preventing the euphoric effects of alcohol or opioids. It is nonaddictive and works best as part of a comprehensive treatment plan, including counseling or therapy, to support long-term recovery.

Read the FDA's statement on concerns over compound pharmacies

GLP-1 drugs popularity for weight loss and treating diabetes, led to a significant supply shortage and the rise of compound pharmacies, which produce customized drug formulations but lack formal approval from regulators. The drugs are ostensibly the same, but manufacturing methods lead to variations in concentration, filler compounds, and more.

Explore a database of generic drugs to trace their origins and identify any safety concerns.

​Why heroin became associated with the grunge world

The drug was popular with several Seattle acts in the early 1990s, with artists like Hole's Courtney Love even publicizing her use in a magazine profile. A 1992 New York Times story on Seattle said the city's principal drugs were "espresso, beer, and heroin."

Multiple sugar substitutes were accidental discoveries when lab workers didn't wash their hands.

View a sample of objects surprisingly derived from crude oil, including chewing gum and lipstick

Crude oil processing produces a variety of fuels and the building blocks for plastics, but it also distills out the hydrocarbons used to make aspirin, Teflon, vinyl, crayons, candles, Tupperware, roofing shingles, asphalt pavement, hair dye, anesthetics, food-grade lubricants, polyester, synthetic rubber, and resins for items like dentures.

Early peptide research focused on isolating the substances from animal tissue

In the first half of the 20th century, peptides including insulin and adrenocorticotropic hormone were isolated from animals to provide life-saving medicines. ACTH was isolated from the pituitary glands of cows and pigs and insulin was isolated from the pancreas of dogs and cows.

How to make LSD

Lysergic acid diethylamide, often shortened to LSD, comes from ergot, a parasitic fungus that can be found in grains. Chemists rearrange the fungus' chemical structure or the structure of an ergot derivative through complex chemical reactions, transforming it into the hallucinogenic bicycle-shaped LSD crystal. Due to the partially synthetic drug's criminalization, many of the details of modern LSD crafting honed by "underground chemists" are kept secret.

A podcast detailing the drug markets of East and Southern Africa

The African continent plays a critical role in the global illicit drug market. Often forgotten when discussing drug trafficking, organized criminal networks in Africa have established relationships with other criminal organizations around the world....