In a concerning development, illicit drug dealers are turning to a group of opioid alternatives that were developed more than six decades ago, mixing them with potent substances like fentanyl and heroin. This dangerous concoction not only poses significant risks to unsuspecting users but also presents a grave challenge to public health officials. The substances in question, known as nitazenes or benzimidazole-subclass opioids, were first created in the late 1950s by the Swiss chemical company CIBA Aktiengesellschaft as alter- natives to morphine due to their potent analgesic effects. However, clinical development was abandoned due to their increased risk of negative side effects.

Despite their initial intended use, these compounds have resurfaced as drugs of abuse, as reported by the U.S. Drug Enforcement Agency. A 2022 World Health Organization report revealed that one of these substances, protonita- zene, is slightly more potent than fentanyl, which itself is approximately 100 times more potent than morphine, according to the DEA.

Recent findings from a 2023 study published in “Pain and Therapy” indicate that protonitazene has been detected in forensic analyses between 2019 and 2021 in cases across the United States, Canada, Europe, and Australia.

The emergence of nitazenes in the illicit drug supply chain in the United States has come to the forefront with a Department of Justice crackdown, resulting in indictments against eight China-based companies and their employees for drug-related crimes. One of these cases involves Jiangsu Bangdeya New Material Technology Co., Ltd., a company based in Jiangsu, China, which openly advertised protonitazene and metonitazene for sale in online advertisements. As a consequence, the company has faced U.S. sanctions from the Department of the Treasury’s Office of Foreign Assets Control.

This company’s connection to illicit drug trafficking in the United States was brought to light after its involvement with a southern Florida drug trafficker, referred to only as co-conspirator 2 in the indictment. Co-conspirator 2, based in Deerfield Beach, Florida, was found to be selling fentanyl in significant quantities to other drug traffickers in South Florida. Starting late in 2021, the dealer began working with Jiangsu Bangdeya New Material Technology, which, in the past 18 months, shipped six kilograms of metonitazene and nine kilograms of protonitazene to the dealer and undercover agents in Florida. Interestingly, the dealer conducted these transactions using bitcoin, a cryptocurrency.

The motive behind this collaboration was clear: the dealer sought chemicals to augment his supply of opioids and enhance their effects on consumers. He regularly ordered 300 to 500 grams of pro- tonitazene or metonitazene from Bangdeya each month. However, this illicit operation was disrupted when law enforcement intercepted one of the Bangdeya packages on June 15. Upon the dealer’s arrest, agents discovered a staggering 8.7 kilograms of mixed opioids.

The resulting mixture was a potent and perilous combination of protonitazene, metonitazene, fentanyl, fluorofentanyl, and heroin. Such opioid cocktails can lead to overdoses among unsuspecting users who often believe they are purchasing prescription opioids like oxycodone. This disturbing trend creates additional challenges for medical professionals and pub­lic health officials.

A recent paper published in JAMA Network Open high­lights the urgency of this issue. Researchers warn that synthetic opioids, including fentanyl ana­logs and nitazenes, are among the fastest-growing types of opioids detected in patients experiencing illicit opioid overdose in emer­gency departments. Clinicians are urged to be aware of these opioids in the drug supply to be adequately prepared to treat patients and an­ticipate the need for multiple doses of naloxone, a medication used to reverse opioid overdoses.

In a study involving 537 overdose patients in the U.S. be­tween 2020 and 2022, researchers discovered that nine individuals tested positive for nitazenes such as brorphine, isotonitazene, metonita­zene, or N-piperidinyl etonitazene, accounting for approximately 1.7% of the total. In contrast, 2% of the patients tested positive only for fen­tanyl.

These findings are deeply concerning, especially in light of the alarming statistics reported by U.S. officials. Between August 2021 and August 2022, there were 107,735 overdose deaths attributed to drug poisonings, with approx­imately 66% involving synthetic opioids like fentanyl, as per the U.S. Centers for Disease Control and Prevention.

The proliferation of these dan­gerous drug cocktails serves as a stark reminder of the urgent need for enhanced vigilance, regula­tion, and education to combat the opioid crisis and protect vulnerable individuals from falling victim to these deadly combinations. Public health authorities and law enforce­ment agencies must work together to curb the flow of these dangerous substances and save lives.

Al DiPasquale