B-327 Evidence of Missed Novel Psychoactive Substances (NPS) in Unexpected Fentanyl Positives
Authors: Campbell G , Schrecker J , Holt A , Hardison M , Heltsley R 
Published: September 2023

Abstract

Background
Recent data published by the CDC indicated that overdose deaths in the United States began to increase significantly in 2020 and continued throughout 2021. Synthetic opioids, such as illicitly-manufactured fentanyl (IMF), have been a primary driver in overdose deaths. There has been a concomitant increase in both the prevalence and diversification of novel psychoactive substances (NPS) and IMF. We performed a blinded secondary analysis of remnant samples to further characterize the incidence in which individuals are encountering NPS when using non-prescribed fentanyl. Various classes of NPS compounds (e.g., designer opioids, designer benzodiazepines, xylazine) were evaluated in samples that were originally positive for fentanyl but did not include a request from the provider for NPS testing to be performed.

Methods
This study was IRB approved. A sampling of 200 urine or oral fluid specimens collected from individuals as part of their routine medical treatment, wherein definitive testing for fentanyl and norfentanyl was performed and the drug and metabolite were both identified above the upper limit of quantitation of the assay, underwent additional analysis for NPS. Samples were excluded from blinded secondary analysis if any NPS testing, regardless of drug class, was originally ordered and performed. Additional testing that was performed included the following classes of drugs: designer opioids, designer benzodiazepines, synthetic cannabinoids, synthetic stimulants, hallucinogens/dissociatives, xylazine, tianeptine, and phenibut.

Results
Specimens within the sample set (N: 200) that were originally positive for fentanyl without a previous request for NPS testing originated from 30 different states within the US. These samples were originally collected between 9/19/2022–1/12/2023. Of those that underwent additional analysis after initial reporting of positive fentanyl results, 117 (58.5%) had at least one analyte within an NPS class identified. Designer opioids (N: 93, 47%), and xylazine (N: 76, 38%), followed by designer benzodiazepines (N: 16, 8%), synthetic stimulants (N: 4, 2%), and hallucinogens/dissociatives (N:3, 2%) were the most frequent compounds detected on a per sample basis. No synthetic cannabinoids were detected within this sample set.

Conclusion
Although much of the national focus around fatal and non-fatal overdoses centers on intentional and unintentional exposures to IMF, healthcare providers and the general public must be made aware of the prevalence of NPS. These compounds, which are often intentionally added to drugs sold as fentanyl to enhance the drug potency, can increase risk for an adverse event. Of paramount importance is that the effects of substances such as xylazine and designer benzodiazepines, which contribute to central nervous system depression, are not effectively reversed by administration of naloxone, a mainstay of harm reduction protocols. Knowledge of the prevalence of these compounds should impact clinical decision-making and individual risk mitigation plans. From a broader perspective, improving understanding of the incidence in which these drugs are found within communities could improve overall surveillance efforts on current drug use trends.