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Polysubstance Abuse: The Changing Shape of the Opioid Crisis

AddictionNews was one of the first news sites to report on the growing crisis known as polysubstance abuse. While this can refer to the combination of any two illicit drugs, most often it refers to the opioid fentanyl mixed with any number of other synthetic drugs, such as carfentanil, ocfentanil, and U4, or non-synthetics such as cocaine and methamphetamine. Since illegal synthetic opioids started showing up in 2009, 55 different compounds have been discovered in the U.S. and 57 in Europe.

Isolation of the active ingredients of the opium poppy led to the discovery of morphine in 1805 and codeine in 1832. Further research led to opioid compounds synthesized in the lab: heroin in 1874, oxymorphone in 1914, oxycodone in 1916, and hydrocodone in 1920. Around the same time, heroin addiction became recognized as a public health problem. Laws restricting the manufacture and distribution of opioids started in 1912.

Synthetic opioids that are not based on naturally occurring compounds began to appear with the discovery of meperidine in the 1930s and methadone in the 1940s. Fentanyl arrived in 1959 and was quickly adopted as an anesthetic, with a potency 50 times that of morphine. This high potency makes fentanyl financially lucrative and easy to transport, leading to its appearance mixed in drugs all over the world.

Synthetic opioids are lethal. The United States has had over 100,000 overdose deaths per year for several years; fentanyl and other synthetic opioids are the main cause of 75% of those deaths. In a recent deep dive into America’s addiction crisis, Axios’ Caitlin Owens says the new polysubstance abuse crisis is “worse than headlines can convey.” Owens says:

The evolving opioid epidemic has morphed again into a multi-drug crisis centered on fentanyl, which is often paired — knowingly or unknowingly — with other illicit drugs.

Owens calls on a variety of sources to present a sobering picture of addiction in America, where in 2022 more than one-quarter of young adults aged 18-25 report a substance use disorder. Here are some other figures Owens cites from 2022:

  • 49 million Americans reported a substance use disorder
  • 30 million Americans reported alcohol use disorder
  • 27 million Americans reported a drug use disorder
  • 6 million Americans reported an opioid use disorder
  • 1.8 million Americans reported methamphetamine use disorder

Owens links the substance abuse crisis with a crisis in mental health that has half of American 18-25-year-olds either reporting a mental illness or substance use disorder. The result is “emergency rooms swamped with psychiatric patients,” growing intolerance, and a shift toward criminal justice containment

The treatment response to an overdose is usually the administration of the drug, naloxone, which reverses opioid impacts rapidly, sometimes too rapidly, leading to symptoms of acute withdrawal. However, naloxone doesn’t have the same efficacy with overdoses from synthetic opioids. The authors of a review of the scientific literature on synthetic opioids note that:

The high potency, rapid onset of action and relatively long half-life of synthetic opioids pose particular challenges for reversal by naloxone.

While the number of young people with substance use disorder is staggering, the prognosis, even with synthetic opioids, is positive. If life can be saved with drugs such as naloxone, and withdrawal symptoms can be managed with methadone and buprenorphine, then “psychosocial interventions” can help unwind the stranglehold of addiction, leading to greater health and life satisfaction.

Written by Steve O’Keefe. First published June 4, 2024.


“The addiction crisis is even worse than headlines can convey,” Axios, May 31, 2024.

“Synthetic opioids: a review and clinical update,” Therapeutic Advances in Psychopharmacology, December 10, 2022.

“Mapping Community Opioid Exposure Through Wastewater-Based Epidemiology as a Means to Engage Pharmacies in Harm Reduction Efforts,” Preventing Chronic Disease, August 20, 2020.

Image of fentanyl chemical structure courtesy PICRYL, public domain.


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