Academy of Diagnostics & Laboratory Medicine - Scientific Short
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Novel psychoactive substances (NPS), also known as “designer drugs” or “legal highs”, are designed to have similar effects to recreational drugs while circumventing legality issues. Use of NPS began to rise in 2010 and, as of 2022, more than 1,000 different NPS have been identified. However, little is known about the impact of these compounds on users due to their constant and rapid emergence into the illicit drug market and the lack of research and prevalence data available for these compounds. Analysis of these compounds is difficult as the compounds are frequently changing, which makes understanding what a patient may have taken even more challenging.
NPS can be broken down into 6 different classes. The other additives (sometimes referred to as miscellaneous) category includes compounds like the veterinary tranquilizers xylazine and medetomidine as well as tianeptine, which is frequently referred to as “gas station heroin”. The designer fentanyl analog category includes compounds like carfentanil, or elephant tranquilizer. The designer benzodiazepine category includes bromazolam, which is commonly referred to as fake Xanax. Designer opioids include the nitazene compounds, most of which are more potent than fentanyl. Designer stimulants include the compounds that are frequently found in “Molly” or “ecstasy” like methylmethcathinone and pentylone. Synthetic cannabinoids are compounds designed to mimic the effects of marijuana and are frequently sold as “K2” or “Spice”. Since the majority of these compounds aren’t sold in stores, are they found in clinical urine specimens? Are multiple NPS found in one patient specimen?
The Quest Diagnostics second generation method analyzes 88 NPS in urine. The method is updated annually to ensure the most recent and prevalent NPS are included in the panel. In a retrospective analysis of urine specimens submitted for NPS testing in 2024, 8,384 specimens were positive. Most of these (65%) were positive for 1 NPS class, but 35% were positive for 2 or more NPS classes. Six patients were positive for 5 of the 6 NPS classes; all 6 were positive for every class except synthetic cannabinoids.
In total, 72 different NPS were seen in patient specimens in 2024. The most commonly seen NPS was xylazine, which was seen in 52.0% of positive specimens (4,360 of 8,384). It was usually seen with fentanyl. Designer fentanyl analogs were positive in 44.3% of positive specimens (N=3,717) with fluorofentanyl and acetyl fentanyl as the most commonly seen fentanyl analogs. Designer benzodiazepines were seen in 21.5% of positive specimens (N=1,806). Bromazolam was the most commonly seen designer benzodiazepine. Designer opioids were seen in 6.6% of positive specimens (N=552) with pyrrolidino hydroxynitazene, a nitazene metabolite, seen most commonly. Designer stimulants were the least positive of the 6 NPS categories and were seen in 4.0% of positive specimens (N=334) with dimethyl pentylone seen most frequently. Synthetic cannabinoids were seen in 17.6% of positive specimens (N=1,473), with the butanoic acid metabolite of MDMB-4en-PINACA seen most often.
With over 8,000 specimens positive for NPS and 72 different NPS seen in various combinations, NPS are a concern in patients. Understanding NPS prevalence in the clinical population and the variety of compounds seen in clinical specimens can help both clinicians and laboratory personnel understand the importance of NPS testing. Knowing which NPS is present in a specimen may help guide treatment, as certain NPS respond to naloxone treatment while other NPS may result in accelerated withdrawal symptoms.
