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Novel Psychoactive Substances: At the epicenter of an unrelenting drug epidemic

Designer or synthetic drugs known as novel psychoactive substances, or NPS, are designed to mimic the effect of controlled substances and/or illicit drugs and are routinely chemically altered to enhance drug effects and evade tracking by law enforcement.2,3 NPS have been implicated in overdose and mass-poisoning events,1 and there has been a dramatic increase in NPS detection in the US,4 posing a growing public health threat to our communities.

Xylazine and fentanyl analogs are rising threats

Two NPS classes—other illicit additives (xylazine) and fentanyl analogs (acetyl fentanyl)—are frequently found in specimens and contribute to the nation’s misuse crisis.6 We recently analyzed the results of our NPS panel, and the data highlighted alarming trends.

52% of NPS-positive specimens contained xylazine—the most common NPS detected7

44% of NPS-positive specimens contained both xylazine and designer fentanyl analogs7

Overdose deaths from fentanyl laced with xylazine jumped 276% in just 3 years8

More than one-third of positive specimens contained compounds from 2 or more NPS classes7
Download infographic

Traditional testing may miss Novel Psychoactive Substances

NPS may supplement traditional drugs of abuse and can be more potent and harder to detect.1,2 As new compounds continually appear on the drug market, detecting them via presumptive immunoassay or point-of-care testing is challenging because they:

Can be present in counterfeit drugs

Can cause more severe drug-to-drug interactions

Are often found in combination with other substances

Are often consumed unknowingly

Comprehensive, definitive testing in a fast-paced NPS market

The Drug Monitoring, NPS panel simultaneously identifies a broad array of NPS classes using definitive liquid chromatography-tandem mass spectrometry (LCMS/MS)-based testing and reports out at the class level to help identify misuse.

 

Current drug classes include:

  • Designer fentanyl analogs ie, carfentanil, chlorofentanyl
  • Xylazine and other illicit additives ie, tianeptine
  • Designer benzodiazepines ie, BZS, clonazolam
  • Designer opioids ie, nitazenes
  • Designer stimulants ie, fluorexetamine
  • Synthetic cannabinoids ie, ADB-5Br-PINACA
View test details
omprehensive-testing-736px.jpg

Two NPS of concern: xylazine and fentanyl analogs

Two NPS classes—other illicit additives (xylazine) and fentanyl analogs (acetyl fentanyl)—are frequently found in specimens and contribute to the nation’s misuse crisis.6 As part of the process of bringing the NPS panel to market, we conducted a national NPS surveillance study, retesting nearly 4,000 specimens.6

  • Xylazine was found in nearly 1 in 12 specimens (8.1%) tested, making it the most prevalant single NPS
  • One-third (32.7%) of fentanyl-positive specimens were also positive for xylazine
  • Nearly all (97.7%) specimens positive for xylazine were also positive for fentanyl

Quest Diagnostics offers definitive NPS testing

Since the list of NPS rapidly evolves, Quest has updated the substances tested with this panel, without changing test codes and requiring EHR updates.

Most recent updates to the NPS panel include

  • 26 analytes added to the 6 different NPS classes
  • Removal of parent drugs in Synthetic Cannabinoid Class
  • Individual class order codes available

– (13793) Designer Benzodiazepinesa

– (13794) Designer Fentanyl Analogs

– (13795) Designer Opioids

– (13796) Designer Stimulants

– (13797) Synthetic Cannabinoids

– (13798) Other illicit additives

a Note that there has been a CPT® code change for Designer Benzodiazepines.

Definitive class reporting: “positive” or “negative”

NPS Positivity Report: Assessing the presence of NPS in patients

In the first year of testing using the Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine panel from Quest, more than 8,000 specimens were found positive for NPS— highlighting the evolving complexity of substance use in patient care.

 

This advanced panel detects compounds across 6 NPS drug classes:

•Designer benzodiazepines

•Designer fentanyl analogs

•Designer opioids

•Designer stimulants

•Synthetic cannabinoids

•Other illicit additives

 

More than a third of positive samples contained compounds from 2 or more NPS classes—signaling dangerous poly-substance use.

 

Our NPS Positivity Report provides a state-by-state breakdown and expert insights to help you stay ahead of evolving drug threats in your patient population. Fill out the form below to get your copy.

 

NPS Postivity Report Thumbnail

The rising threat of xylazine in illicit drugs: Download NPS Positivity Report

Fill out the form below to download our analysis of the rising threat of Novel Psychoactive Substances.

Please remember that email, including this web form, is not a secure method of communication. Do not submit personal information, including usernames and passwords, social security numbers, or personal health information through this form.

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References:

1. Iwersen-Bergmann S, Lehmann S, Heinemann A, et al. Mass poisoning with NPS: 2C-E and Bromo-DragonFly. Int J Legal Med. 2019;133(1):123-129. doi:10.1007/s00414-018-1882-9

2. Peacock A, Bruno R, Gisev N, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. Lancet. 2019;394(10209):1668-1684. doi:10.1016/s0140-6736(19)32231-7

3. Mohr ALA, Logan BK, Fogarty MF, et al. Reports of adverse events associated with use of novel psychoactive substances, 2017–2020: a review. J Anal Toxicol. 2022;46(6):e116-e185. doi:10.1093/jat/bkac023

4. The Center for Forensic Science Research & Education. Trend reports. 2024. Accessed February 9, 2024. https://www.cfsre.org/nps-discovery/trendreports

5. Neoh MJY, Carollo A, Lim M, et al. The novel psychoactive substances epidemic: A scientometric perspective. Addiction Neuroscience. 2023(5):100060. doi:10.1016/j.addicn.2022.100060

6. Quest Diagnostics Health Trends. Drug misuse in America 2023: the growing crisis of novel psychoactive substances. December 23, 2024. Accessed February 12, 2024. https://mma.prnewswire.com/media/2303443/Quest_Diagnostics_2023_HT_DM_Report.pdf?p=original

7. Quest Diagnostics NPS report, 2025

8. Kariisa M, O’Donnell J, Kumar S, et al. Illicitly manufactured fentanyl–involved overdose deaths with detected xylazine— US, January 2019–June 2022. MMWR Morb Mortal Wkly Rep 2023;72:721-727. doi:10.15585/mmwr.mm7226a4

 

CPT® codes are based on American Medical Association guidelines and mentioned for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

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