Synthetic opioids and designer benzodiazepines linked to driving impairment

No-one could claim to be unaware of the dangers of driving under the influence of drugs (DUID): drugs can increase the time needed to react, impair coordination, alertness, and cognition, and lower inhibitions, thus encouraging reckless and aggressive driving. In the US in 2021, 10,903 people died in crashes where drugs were involved, which corresponds to 26% of all traffic deaths that year. And because new drugs constantly hit the black market, efforts to tackle the issue can be very challenging.

A new study in Frontiers in Toxicology has now shown the urgent need of extending current tests routinely performed after traffic crashes to cover new drugs. It is the first comprehensive survey to measure the contribution of a broad range of so-called 'new psychoactive substances' to US roadway crashes.

Here we show that new psychoactive substances (NPS), a group of drugs which has rapidly expanded over the past 15 years, are a concern in roadway crashes."

Dr. Roy Gerona, one of the study's corresponding authors and associate professor at the University of California San Francisco

Flying below the radar

NPS, colloquially known as 'designer drugs', 'legal highs', 'herbal highs' and 'bath salts' are drugs not covered by the UN's 1961 Single Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances, but which are deemed by experts to pose a risk to public health. Examples are designer benzodiazepines, synthetic cathinones and cannabinoids, piperazines, and tryptamines. The full range of their effects on physical and mental health is still poorly known, but these can include agitation, psychosis, aggression, and dependence. NPS also contribute to the devastating opioid crisis in the US, as they may contaminate fentanyl supplies, leading to additive toxicity, or be sold instead of fentanyl by dealers.

Most existing urine drug screens do not target NPS, which are typically only detectable through expensive high-resolution mass spectrometry (HRMS) in specialized laboratories.

Here, Gerona and colleagues surveyed the prevalence of NPS in the blood of roadway crash victims in northern and southern California between January and July 2024. They focused on the first 1,000 adult victims of roadway crashes who during that period visited either of two representative trauma centers in Los Angeles and Sacramento, and from whom blood was drawn during routine emergency care.

Through HRMS, they confirmed the presence of NPS in blood from 17 patients (2%). Among these, bromazolam was the most frequent (seven patients), followed by para-fluorofentanyl (four patients) and mitragynine (three patients). Acetyl fentanyl, N-methyl norfentanyl, protonitazene, etizolam, and xylazine were each detected only once.

"The types of NPS detected in our first 1,000 cases reflect the prevailing NPS found in nationwide surveillance studies, where depressants of the central nervous system such as designer benzodiazepines and fentanyl analogs predominate," summarized Gerona.

A mixed bag

The results also showed that users frequently mix NPS with other drugs. All but two of the 17 patients with NPS in their blood were also positive for at least one traditional recreational drug. Nine had taken a sedative NPS together with a stimulant such as cocaine or methamphetamine, while 11 had combined NPS with traditional opioids. A further 273 (27%) patients tested positive for traditional recreational drugs, but not for NPS.

"The codetection of NPS like bromazolam and para-fluorofentanyl with common drugs of abuse like fentanyl, methamphetamine and cocaine in our cohort implies either the adulteration of common drugs with NPS, or the intentional simultaneous use of multiple drug classes," said Gerona.

"For example, benzo-dope, the combination of a designer benzodiazepine and fentanyl or another opioid, has been trending in the unregulated drug market. In other cases, users intentionally combine a stimulant and a depressant, thinking that their opposing effects may mitigate each drug class's toxic effects."

Since the present study, the authors have continued to collect data from the study population. Their intention is to gather as much evidence as possible to inform changes to existing guidelines for determining drug-induced driving impairment.

"People should be aware that in particular synthetic opioids, which are often found as adulterants, pose a significant health risk due to the strength of their sedating effects, which can impair a user's ability to drive. For example, protonitazene is 130 times more potent than morphine and even more potent than fentanyl," warned Dr. James Alan Chenoweth, an associate professor at the University of California Davis and the principal investigator of the study.