How did an opioid deadlier than fentanyl go mainstream? | Babbage podcast

Key Concepts

• Nitazenes: A class of potent, illicit synthetic opioids.
• Active Metabolites: Compounds produced when the body breaks down a drug, which can themselves have pharmacological effects.
• Naloxone: An opioid antagonist used as an antidote for opioid overdose.
• Harm Reduction: Strategies aimed at reducing the negative consequences associated with drug use.
• Drug Prohibition: Policies that aim to ban the production, sale, and possession of drugs.

Nitazenes: A New Opioid Threat

This discussion focuses on nitazenes, a group of highly potent illicit synthetic opioids that have emerged as a significant concern globally. While invented in the 1950s by chemists seeking new painkillers, they were deemed too dangerous for approval due to the difficulty in administering safe doses and the risk of severe side effects or death. They remained largely off the grid until 2019, when they began appearing on the illicit drug market in Europe, surprising authorities. Since then, their presence has increased, leading to clusters of overdoses in Europe, Africa, Australia, and America. A notable cluster occurred in Ireland in 2023, where 77 overdoses were recorded in Dublin and Cork over a few weeks, initially mistaken for a bad batch of heroin. Authorities later confirmed the substance was nitazenes, not heroin.

Chemistry and Effects of Nitazenes

Nitazenes function as opioids, mimicking the effects of drugs like heroin. Users seek the intense analgesic (pain-relieving) and euphoric effects. However, their extreme potency makes them highly dangerous. Overconsumption can lead to severe nausea, vomiting, fever, and, most critically, respiratory depression, where breathing slows to the point of cessation, resulting in overdose.

A particularly dangerous characteristic of some nitazenes, such as etonitazene, is the presence of active metabolites. When the body metabolizes these drugs, one of the resulting compounds is itself a nitazene, and in some cases, this metabolite is even more potent than the original drug. This poses a significant challenge for overdose response, as a standard dose of the antidote, naloxone, might not be sufficient to counteract the effects of both the initial drug and its more potent metabolite, potentially leading to a "second hit" of overdose.

Mode of Consumption and Accidental Exposure

A key factor contributing to the danger of nitazenes is that most users do not intentionally seek them out. They are often unknowingly present as adulterants in other illicit drugs, such as heroin, cocaine, or MDMA. Small amounts, even micrograms, can be present, and if a user believes they are taking a familiar substance at their usual dose, the unexpected presence of a much more potent nitazene can lead to accidental overdose. Nitazenes can be consumed in various forms, including powder, tablets, injection, or snorting, and their presence can be entirely unexpected, meaning users may not have the antidote readily available or take other necessary precautions.

Factors Driving the Rise of Nitazenes

The increasing prevalence of nitazenes on the illicit market is attributed to several factors:

• Potency and Business Appeal: Despite their danger, the high potency of nitazenes makes them attractive to drug producers, smugglers, and dealers. Less material is needed to achieve the desired effect, making smuggling easier. Stories exist of nitazenes being concealed in everyday items like dog food tins or lubricants.
• Supply-Side Disruptions:
  • Fentanyl Regulation: In the 2010s, the US, in particular, intensified efforts to crack down on fentanyl and its precursors, encouraging other countries to follow suit.
  • China's Bans: In 2019, the same year nitazenes began appearing on the market, China implemented bans on fentanyl precursors, a significant move given China's role as a major producer of illicit drugs.
  • Afghanistan Opium Ban: In 2021, the Taliban took control of Afghanistan, the world's primary producer of opium (a precursor for heroin), and banned opium cultivation. Historically, such disruptions have led to supply shocks in Europe.

These supply-side changes appear to have prompted illicit drug producers and smugglers to innovate and seek alternatives, leading to the emergence of nitazenes.

The Paradox of Prohibition

The emergence of nitazenes raises questions about the effectiveness of drug prohibition policies. The argument is made that attempts to outlaw drugs, without accompanying harm reduction measures, can inadvertently drive innovation in the illicit drug market, leading to the development of even more dangerous substances. This creates a "whack-a-mole" scenario where authorities address one drug, only for another, potentially more dangerous, substance to emerge.

Responses and Harm Reduction Strategies

Different countries are adopting varied approaches to the nitazene threat:

• Public Warnings: Ireland has taken a direct approach by issuing public warnings, even displaying signs on motorways stating "dodgy heroin, don't take it." This strategy has reportedly yielded positive experiences.
• Cautionary Approach: The UK, conversely, expresses concern that warning people about nitazenes might inadvertently attract users seeking a powerful high, given their potent opioid nature.

However, a consensus among medical professionals and addiction service providers emphasizes the importance of harm reduction. Key strategies include:

• Naloxone Accessibility and Education: Making the opioid antidote, naloxone, more widely available (it is often a prescription drug) and educating the public, including friends and family of users, on its proper use is crucial. Given the potential for more potent metabolites, carrying and administering multiple doses of naloxone might be necessary.
• Knowledge and Awareness: Educating individuals about the risks associated with nitazenes and the potential need for increased antidote dosage is vital.
• Improved Access to Safer Drugs: Some experts advocate for improving access to more established and, at the end of the day, safer drugs like heroin as part of treatment programs. Switzerland, for example, has seen success with this approach, though cultural stigma has limited its broader adoption.

Conclusion

The rise of nitazenes highlights the complex and often counterproductive nature of solely punitive drug prohibition policies. The potent and dangerous nature of these synthetic opioids, coupled with their often-unintentional consumption, poses a significant public health challenge. A comprehensive approach that prioritizes harm reduction, increased access to antidotes like naloxone, and potentially explores alternative drug policies, such as supervised access to safer substances, is essential to mitigate the ongoing threat posed by nitazenes and prevent the emergence of future, even more dangerous, illicit drugs. The multigenerational "war on drugs" is presented as problematic, with evidence suggesting that simply banning drugs is ineffective.