The History of Synthetic Opioids

The use of plant materials to relieve suffering, treat illness or conduct religious ceremonies has a long history. Occasionally, the Industry News will look more closely at the history of a standard drug of interest in the toxicology industry.

In the late 1920s the world understood the innate dangers of morphine and heroin. Consequently, chemists began experimenting with other compounds in their attempts to develop a pain reliever that was as effective as morphine but without its damaging side effects. The class of drugs they developed is what we now call synthetic opioids. These drugs have similar properties to opium-derived painkillers (or “opiates”) but were entirely synthesized in the lab. All have different properties and uses. But just like opiates, synthetic opioids can be very effective as well as very dangerous.

Two synthetic opioids, pethidine (aka meperidine or Demerol) and methadone, were developed by German scientists in the 1930s, likely as part of Adolf Hitler’s goal to make Germany independent of other countries and stop importing raw materials like opium. After WWII, the Allies confiscated German research, and American companies bid on the right to produce the new painkillers. Because pethidine is not an opiate, its capacity for addiction went unrecognized for many years, but it is now a Schedule II narcotic prescribed most often for stomach and intestinal conditions such as diverticulitis. Methadone was marketed in the U.S. in 1947, and its ability to reduce opiate cravings was noticed almost immediately. By the mid-1960s, doctors in New York City were desperate to stop the rapid spread of disease from one heroin addict to another. Researchers at the Rockefeller Foundation found that methadone stopped an addict’s obsessive need for heroin, and the protocols they developed were the beginning of methadone clinics and medication-assisted treatment (MAT).

Other synthetic opioids include fentanyl, propoxyphene and tramadol. Deadly in even tiny quantities, fentanyl was developed in Belgium in the 1950s initially as an anesthetic. Its extreme potency makes it useful for truly severe pain, but even 3 milligrams can kill an average-sized man. Differently dangerous, propoxyphene was prescribed regularly for mild to moderate pain until fairly recently. In 2010 the FDA asked for a voluntary recall based on the drug’s weak painkilling abilities, addictiveness, and association with suicide and with heart arrhythmia. Propoxyphene was largely replaced by tramadol, which was developed in Germany in 1962 but only became available in the U.S. in 1995. Tramadol generally has a lower incidence of abuse, except by those who have a history of substance abuse. Interestingly, although tramadol was initially lab-borne, a flowering evergreen in sub-Saharan Africa has since been found to contain significant concentrations of tramadol and is used locally to treat a variety of conditions, including epilepsy and malaria.