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Challenges in Identifying Novel Psychoactive Substances and a Stronger Path Forward

The importance of non-targeted testing to keep pace with a rapidly evolving synthetic opioid market.
Notes From the Field
Date Published
June 11, 2022

The synthetic opioid market in the United States is constantly evolving. Once a new substance is identified, it may only be prevalent for three to six months before it’s replaced by something new and yet to be identified by forensic laboratories.

For example, over one weekend in July 2018, Philadelphia-area hospitals experienced a surge of more than 100 patients with suspected opioid overdoses. Following the administration of naloxone, patients would become combative – an unusual reaction for an opioid overdose.

To help local public health and public safety agencies identify what was causing this troubling trend, the NPS Discovery drug early warning system at the Center for Forensic Science Research and Education (CFSRE) acquired a sample of “Santa Muerte,” the drug linked to the large number of overdoses. Advanced mass spectrometry analysis found within the sample a combination of fentanyl, heroin, and a synthetic cannabinoid – a combination not often seen in the region. Given the unique side effects that overdose patients were experiencing, it was thought this may be a synthetic drug combination worth tracking closely.

However, substances containing fentanyl and synthetic cannabinoids did not last long and were only a fraction of the whole drug supply in the region. After about six to nine months following the July overdoses involving “Santa Muerte,” these substances were largely replaced by new synthetic drug products, primarily fentanyl cut with xylazine.

This dynamic drug environment in the United States places an incredible burden on forensic laboratories. For laboratories to develop tests that identify a substance, to validate those tests and then implement those tests in casework, six to nine months is a very short turnaround time.

To keep pace with an ever-evolving drug market, forensic laboratories should consider developing workflows that allow for non-targeted testing protocols, including data processing and interpretation strategies, such as data mining and sample mining. While these workflows require an investment of resources to implement, they’ve been shown to better position laboratories to not only find specific drugs believed to be present in a sample, but to also identify accompanying novel psychoactive substances (NPS) that may be unexpected. These forward-looking and retrospective workflows can help laboratories identify new drugs and share information on the substances, which is a critical component to support public health and safety.

Forensic Labs Adapting to Evolving Synthetic Opioids

Synthetic opioids are a public health and public safety threat in the United States. As chemically manufactured drugs, new synthetic opioids may be distributed as powder or tablets and may be mixed with more traditional opioids. These illicit substances carry an unknown potency as well as sometimes severe adverse side effects and health risks.

Historically in the United States, the heroin supply was truly heroin up until about 2005 to 2008. Around that time, fentanyl was introduced into the opioid supply across various parts of the country. Initially, heroin was cut with fentanyl to varying degrees, but today fentanyl has largely taken over. Cases involving heroin are down across the country and, in some areas, it may be almost non-existent.

For a number of years now, fentanyl has been overwhelmingly the primary synthetic opioid. Following the introduction of fentanyl into the drug market, additional synthetic opioids emerged, including numerous fentanyl analogues. Fentanyl analogues are produced via slight chemical modifications to fentanyl, some rendering the drug less potent but others making the drug more dangerous. There have been certain fentanyl analogues, such as acetylfentanyl, furanylfentanyl, and carfentanil, that have become prevalent over time and have been implicated in thousands of deaths.

Adjusting to the trends of emerging synthetic opioids, the forensic laboratory community became experts in identifying fentanyl analogues since they all have similar chemical fingerprints. As forensic scientists, we learned what to expect and came up with processes for how we could characterize fentanyl-related substances on our instruments. On the toxicology side, processes were developed for how our toxicologists could interpret these cases that involved fentanyl analogues, and we were in some ways prepared for what was coming next because we knew it would be just a slight modification. The first challenging part was figuring out what that slight modification was going to be.

After the DEA scheduled all fentanyl-related substances in early 2018, fentanyl analogues faded from the market, and today it is rare to find fentanyl analogues. While this drug market shift resulted in less overdose deaths related to fentanyl analogues, there have been secondary consequences in that drug manufacturers producing synthetic opioids have continued producing synthetic opioids – but now they’re producing different drugs. We’ve entered an era of a whole new opioid market with drugs exhibiting different chemical properties. Certainly, they’re still opioids at the end of the day, but they are structurally distinct from fentanyl or heroin, and they behave differently both chemically and pharmacologically to varying degrees.

This reset and new evolution of the synthetic opioid landscape has created numerous challenges for forensic laboratories because we’ve had to develop new methods to be able to test for these new drugs and have had to develop new workflows and data analysis schemes. To further complicate the matter, sometimes laboratories aren’t aware that these new synthetic opioids exist and these substances can go undetected during forensic testing in drug material casework or during death investigations.

Key Tools and Workflows for Identifying New and Emerging Synthetic Drugs

To keep pace with the current recreational drug landscape, laboratories in the United States should consider investing in practices that are able to detect new and emerging synthetic drugs. One of the most effective ways to accomplish this is through non-targeted testing techniques, such as sample mining and data mining.

With support from NIJ, the CFSRE and its scientists were able to demonstrate how novel sample-mining and data-mining workflows are valuable tools for the early identification and discovery of NPS and emerging drug trends.

For example, at CFSRE we maintain a huge sample-mining database. We actively test for almost 1,000 drugs that we’re monitoring for at a single time and the database is always expanding. Since we know that any type of new drug could emerge next month, we prepare ourselves now so we’re ready when a new drug first appears in the supply. The goal is to detect it on first instance and report out relevant information right away.

Our data-mining workflow also uses archived datafiles (a historical perspective of the drug market) to identify drugs seen in previous cases, pull together trends, and evaluate the epidemiology of some of these new drugs, including their prevalence, and identify when they truly first emerged.

Funded by NIJ, NPS Discovery remains in operation as a national drug early warning system and warehouses an open-access database that allows laboratories to rapidly share and consume information on novel psychoactive substances as soon as they are found. The database also includes reports on other vital drug information, including detections in drug materials, demographics, geographical distribution, and impacts on drug using communities.

When our NPS Discovery program issues a public health alert involving a new drug, we provide recommendations for laboratories, medical examiners, and others on how they can best identify and track these new substances in their testing. Our public alerts also outline the impacts we’re seeing, including numbers of deaths observed to date for a drug.

For other forensic laboratories, we often suggest they prioritize analytical testing of seized drug samples taken from drug overdose scenes in death investigations. If the drug powder is prioritized over toxicology testing, their scientists will know what to look for when they test the toxicology sample. From a toxicologist’s perspective, it may be beneficial to know what was the last drug that person may have used before they died.

We also suggest that laboratories share data on synthetic opioid drug seizures with local health departments, medical examiners, and coroners. If law enforcement is testing a drug powder and they’re able to quickly disseminate that information to the clinicians, medical examiners, and others who are going to see the impacts of that drug powder downstream, it helps speed up not only the processing of those cases, but also the dissemination of information about the substance.

Particularly in the synthetic drug realm, where there can be hundreds of drugs out there, if someone knows what they’re looking for during testing, it can not only make the testing processes easier but also speed up the time between sample submission and reporting. For practitioners, it is valuable to have some indication as to what the five to ten drugs most commonly seen by law enforcement are in a given jurisdiction. This information is going to be helpful in determining if a specific jurisdiction sees more opioids than stimulants, for example, or if a jurisdiction sees more benzodiazepines than synthetic cannabinoids. While securing the resources to analyze the local drug market and know its key players can be a challenge, this knowledge can be vital for appropriate public health and public safety awareness and response. A better understanding of drug markets allows scientists to prioritize certain drugs and try to get answers quicker.

In the end, for every emerging drug, the sooner we know what the drug is and where it is appearing, the sooner we can begin to address the issues surrounding its impacts.

About Notes from the Field

The National Institute of Justice (NIJ) is the research, development, and evaluation arm of the U.S. Department of Justice. NIJ aims to address the critical questions of the criminal justice field, particularly at the state and local levels.

NIJ posts the Notes from the Field series to allow leading voices in the field to share their strategies for responding to the most pressing issues on America’s streets today.

Notes from the Field is not a research-based publication. Instead, it presents lessons learned by on-the-ground criminal justice leaders, from years of experience and thinking deeply about criminal justice issues.

Date Published: June 11, 2022