Prescription and recreational use of benzodiazepines in the United States is on the rise, and may become another epidemic. Particularly worrisome is the recreational use of designer benzodiazepines, as they are marketed as “legal highs,” Maximo J. Marin, MD, and Xander M. R. van Wijk, PhD, wrote in the latest issue of Clinical & Forensic Toxicology News (CFTN).

CFTN is a quarterly AACC/College of American Pathologists (CAP) educational newsletter for toxicology laboratories and individuals with an interest in toxicology. Each issue highlights topics of interest to the clinical and forensic toxicology fields. The June edition of CFTN highlights the concern over designer benzodiazepine drugs— something the current opioid crisis could be masking, chair of the newsletter’s editorial advisory board Kamisha Johnson-Davis, PhD, DABCC, FACB, an associate professor at the University of Utah’s Department of Pathology, told CLN Stat.

“Clinical laboratories should be aware that designer benzodiazepines are gaining in popularity and may be causing apparent ‘false positives’ with benzodiazepine immunoassays,” van Wijk told CLN Stat. In addition, with so many benzodiazepines that do not have Food and Drug Administration (FDA) approval on the illicit market, conducting analytical tests is a challenge for labs.

Alprazolam (Xanax), clonazepam (Klonopin), lorazepam (Ativan), and diazepam (Valium) are among the most common types of benzodiazepines in the United States, although they’re often found on the illicit market as well. “This use is risky, however, because fentanyl in counterfeit Xanax tablets has caused multiple fatalities in unsuspecting users,” the authors stated.

Use of designer drugs on the dark net is an even more insidious trend. Designer benzodiazepines are synthetic functional or structural analogs of benzodiazepines that are sold as research chemicals and aren’t intended for human consumption. Clandestine labs are finding and producing these drugs, many of which were synthesized as drug candidates by pharmaceutical companies, according to Marin and van Wijk. “They even appear where users don’t expect them, such as in counterfeit alprazolam tablets,” van Wijk said.

Immunochemical tests and enzyme-linked immunosorbent assays have been fairly effective at detecting non-FDA–approved benzodiazepines. “Ideally, toxicology laboratories should include these drugs in their confirmatory methods,” the authors wrote. The problem, however, is mass spectrometry (MS) methods don’t typically cover the newer designer benzodiazepines and are likely to yield false-positive results.

The authors describe some methods that might make it easier for toxicology labs to track and identify new drugs, such as liquid chromatography-tandem MS and high-resolution MS(LC-HRMS). “Although LC-HRMS instruments are expensive, this technique has many advantages in the evolving world of designer drugs,” they observed.

The June issue of CFTN addresses other timely concerns:

  • A case report that describes how some hypertensive medications prescribed during pregnancy can produce a false-positive result for the fentanyl urine drug screen;
  • Several deaths related to contaminated synthetic cannabinoid exposure in Illinois; and
  • Whether imatinib mesylate should be added to the list of cancer medications for therapeutic drug monitoring.

CFTN is an educational service of the Forensic Urine Drug Testing (FUDT) Accreditation Program co-sponsored by AACC and CAP. Individual subscriptions are also available; the regular price is $65, and AACC members pay $45. “Science lovers from various disciplines would be interested in subscribing to CFTN because the newsletter spotlights current topics in the field of toxicology and in the news,” Johnson-Davis said. Subscribers are eligible to receive 4 ACCENT continuing education credits per year, 1 credit per quarterly issue.