P-059 - (Poster #59) Should I test for Novel Psychoactive Substances (NPS) in Clinical Specimens?

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 cover a wide range of compounds. Xylazine is a veterinary tranquilizer that is mixed with fentanyl to lower cost and enhance opioid effects. Tianeptine is available in some states as “gas station heroin”. Carfentanil is a large animal tranquilizer and is 100 times more potent than fentanyl and 10,000 times more potent than morphine. Designer benzodiazepines are taken as an alternative to traditional benzodiazepines, such as alprazolam or diazepam. Synthetic cannabinoids are seen as an alternative to marijuana. Testing for these compounds can give physicians a better understanding of overall patient health.

Purpose/Objectives:

In this study, testing data from a large United States diagnostic laboratory was used to assess the prevalence of NPS in the clinical patient population. This was done through a retrospective analysis of urine specimens submitted to Quest Diagnostics for NPS testing between November 2023 and December 2024. Positivity rates and trends were determined for 85 NPS compounds in 6 NPS categories: designer fentanyl analogs, designer benzodiazepines, designer opioids, designer stimulants, synthetic cannabinoids, and other illicit compounds. The purpose of this retrospective analysis was to determine prevalence of these 6 NPS classes overall, as well as the prevalence of these compounds in each state in the United States.

Methods:

NPS testing at Quest Diagnostics looks for NPS in urine specimens and reports out results in 6 NPS categories. The designer fentanyl analog category includes carfentanil, fluorofentanyl, and others. Designer benzodiazepines includes bromazolam, clonazolam, and others. Designer opioids include various nitazene compounds. Designer stimulants include dimethyl pentylone, eutylone, and others. Synthetic cannabinoids include MDMB-4en-PINACA, ADB-BUTINACA, and others. Other illicit compounds include xylazine, tianeptine, and others. Metabolites are included where appropriate. Testing was performed using a semi-quantitative method that was previously validated according to CLIA and Quest Diagnostics requirements. A linear calibration curve was used and all compounds had limits of detection between 0.5 ng/mL and 10.0 ng/mL. As NPS on the market change frequently, the NPS method at Quest is updated on an annual basis to ensure the analysis method is up-to-date with what is in purchased drug material. The first method update occurred in December 2024 and included the addition of 25 additional analytes and metabolites of interest.

Results:

In total, 8384 specimens were positive for at least 1 NPS. The majority of positive specimens (64.7%) were positive for only 1 of the 6 NPS categories, while 26.2% were positive for 2 categories, 6.6% were positive for 3 categories, 2.4% were positive for 4 categories, and 0.1% were positive for 5 categories.

Of the 8,384 specimens that were positive for at least 1 NPS, 52.9% were positive for an NPS in other illicit compounds; 44.3% were positive for designer fentanyl analogs; 21.5% for designer benzodiazepines; 17.6% for synthetic cannabinoids; 6.6% for designer opioids; and 4.0% for designer stimulants.

Xylazine, a compound in the other illicit compounds class, was the most positive analyte and was seen in 52.0% of the total number of positive specimens. Tianeptine was seen in 0.8% of positive specimens. Compounds from this class were prevalent across the United States.

The most commonly detected designer fentanyl analogs were fluorofentanyl (29.3% of positive specimens) and acetyl fentanyl (27.3%), which were always detected with fentanyl and/or norfentanyl. Carfentanil was seen in 47 specimens. Designer fentanyl analogs were frequently seen with xylazine, a combination that was seen in 26% of positive specimens. The highest prevalence of these compounds was from Oregon and Illinois.

The most commonly detected designer benzodiazepines were bromazolam (12.2% of positive specimens) and its metabolite hydroxy-bromazolam (16.3%). They were seen both by themselves (8.7% of positive specimens), as well as mixed with other NPS classes like other illicit additives (10.5%) and designer fentanyl analogs (7.3%). Compounds from this class were more prevalent in the northeast and Midwest.

The most commonly detected designer opioid metabolite was pyrrolidino hydroxy-nitazene (5.3% of positive specimens), and the most commonly detected designer opioid parent compound was metonitazene (1.3%). Designer opioids were primarily seen in specimens from the eastern part of the United States. The most commonly detected designer stimulant was dimethyl pentylone (2.6% of positive specimens) and were most prevalent in specimens from New York and Florida. The most commonly detected synthetic cannabinoid was the metabolite for MDMB-4en-PINACA (17.2% of positive specimens), which was seen in specimens from across the United States.

Conclusions/Implications for future research and/or clinical care:

In the specimens that were analyzed at Quest Diagnostics for NPS between November 2023 and December 2024, 8384 were positive for at least 1 NPS. The positive specimens included analytes from all 6 NPS categories, with other illicit compounds accounting for the largest percentage of positive specimens. NPS do not show up when analyzing for traditional drugs of abuse. Performing NPS testing can give a better indication of patient positivity for compounds that may have been illicitly obtained. As the variety of NPS continues to change and evolve, testing clinical specimens using updated NPS methods is important for understanding what a patient may have taken.