2023 NPS Summary

2023 NPS Summary

Healthcare providers throughout the United States who chose to utilize Aegis’ expansive NPS testing menu were afforded the opportunity to address the use of various designer substances with their patients, with a summary of identified substances provided below.

Aegis offers healthcare providers the opportunity to evaluate their patients’ substance use more completely by offering testing for numerous classes of novel psychoactive substances (NPS). Without advanced testing, use of these substances by individuals may go undetected, which can interfere with prescribed therapy and could result in severe adverse events, including overdoses. In 2023, Aegis detected over 74,100 NPS analytes in healthcare samples when testing was ordered (Figure 1). This is an underrepresentation of actual positivity, as many samples received at Aegis do not include orders for NPS testing. Designer opioids were detected most frequently, followed by miscellaneous NPS, designer benzodiazepines, synthetic cannabinoids, and synthetic stimulants. In many instances, samples included multiple analytes from one drug class and/or analytes from multiple classes, such as xylazine (in NPS-Misc. class) and designer opioids. The following figures supply a more granular analysis of the NPS detected in the fourth quarter as part of Aegis’ enhanced NPS testing options.

 Figures 2a and 2b. Designer opioids are sometimes referred to as fentanyl analogs (fentalogs) however, other non-fentalogs are increasingly detected in Aegis’ testing. Fluorofentanyl and despropionyl fluorofentanyl continue to be the most frequently observed analytes in 2023 (Figure 2a). Other top designer opioids include fentanyl analogs and nitazenes. Nitazene analogs continue to be detected, which in many cases are more potent than fentanyl (Figure 2b). The increasing detection of non-fentanyl opioids found in the illicit drug supply may be a response by clandestine labs to circumvent the increased regulation of fentanyl analogs by both US and international drug scheduling bodies. One trend to monitor is norcarfentanil, which is a metabolite of carfentanil, which is one of the most potent fentanyl analogs to be detected in the illicit supply.


Aegis began offering testing for additional NPS in the second quarter of 2021. Xylazine, which is approved as a veterinary tranquilizer, continues to be most often detected in this group, more than doubling in detection since the third quarter. The parent drug was detected in more than 17,700 samples in 2023 while the metabolite was detected more than 7,900 times (Figure 3a). Xylazine is a common adulterant found in heroin and illicitly manufactured fentanyl, where it is sometimes referred to as “tranq-dope” and is increasingly detected in overdose deaths involving illicit opioids. It poses a particular danger because it does not readily respond to naloxone reversal. Phenibut, tianeptine, and ketamine and PCP analogs were detected in lesser quantities. A new addition in Aegis’ menu in late 2023 was medetomidine, which, like xylazine, is an adulterant which may not respond well to naloxone reversal (Figure 3b).

The most frequently detected designer benzodiazepines in 2023 were bromazolam and 8-aminoclonazolam, a metabolite of clonazolam, with a new bromazolam metabolite added in late 2023 (Figure 4a). The other top benzodiazepines detected by quarter are shown in Figure 4b. Designer benzodiazepines are often found as counterfeit versions of commonly recognized prescription benzodiazepines, such as alprazolam 2mg “bars” and, in many cases, more than one designer benzodiazepine is present in counterfeit tablets.

A synthetic cannabinoid marker was detected over 2,900 times in 2023. A metabolite of MDMB-4en-PINACA was detected in 1,695 samples (Figure 5a), with lesser quantities of other cannabinoids, including 4F-MDMB-BUTINACA, ADB-BUTINACA, 5F-MDMB-PICA and metabolites (Figure 5b). Recent bans from other countries have impacted the production and availability of synthetic cannabinoids. This is believed to be the reason for newer compounds appearing in the recreational drug supply.

N,N-dimethyl pentylone and pentylone, believed to be a metabolite or process impurity in the production of N,N-dimethyl pentylone, were the most frequently detected stimulants in 2023 (Figure 6a). Eutylone, which was the most frequently detected cathinone until 2022, appears to be declining with other stimulants increasing. The rise of N,N-dimethyl pentylone and the decline of eutylone is a great example of the dynamics of the NPS supply. In all, stimulants were detected in over 1,300 samples in 2023, with the remaining most commonly detected per quarter highlighted in Figure 6b.

The following maps illustrate the detection, by state, for individual NPS classes (Figures 7-11) as well as total NPS analytes detected (Figure 12) in 2023.