The devastating, drug overdose epidemic in the U.S. killed over 105,000 people last year, most from the synthetic opioid fentanyl. But while fentanyl has dominated the headlines, talk in public health circles has shifted to a new illicit drug on the street: xylazine.
Xylazine, also known as “tranq” or “zombie drug,” has infiltrated the illicit fentanyl market, generally in the form of a fentanyl-xylazine combination. The nonopioid tranquilizer xylazine likely extends the effects of opioids, bringing new and unique challenges. Commonly used as a veterinary sedative, xylazine can cause injection site wounds that lead to necrosis or amputation.
Its rise spotlights the dynamic and ever-changing nature of the illicit drug market. New substances— bath salts, spice, K2, synthetic cannabinoids and fentanyl analogs—continually appear there, given the ready availability of their chemical precursors, and arising from attempts to skirt laws and regulations, or simply out of consumer preference, with alarming frequency.
In our modern era of illicit synthetic drugs that kill many thousands of Americans every year, we need a new model of warning people about dangerous drugs that tells them the quantity of each drug present in what is sold, including any new substances in these drugs.
At the National Institute of Standards and Technology, where we have created the Rapid Drug Analysis and Research (RaDAR) program, we regularly encounter two or three new substances per month. NPS Discovery, a program run by the Center for Forensic Science Research and Education, identified 137 new substances in the U.S. in the last five years. The European Monitoring Center for Drugs and Drug Addiction (EMCDDA) identified 370 new substances in Europe in 2020 alone.
Keeping up with changes in the drug supply requires timely and comprehensive data, currently hard to obtain because of a lack of uniform reporting, as well as case backlogs and limitations in technology. Most information comes from three disciplines: forensic drug chemistry, forensic toxicology and public health. Each has different objectives, constraints and workloads that may hinder timely alerts about deadly new drugs.
Forensic drug chemists identify the illegal substances in samples for criminal investigations. Identifying and reporting cutting agents, diluents or substances that are harmful but not illegal, like xylazine, is often not required and may be overlooked in these investigations. Their laboratories also often face large backlogs, prohibiting timely reporting of data. In 2019, the average drug chemistry laboratory in the United States had a backlog of 1,862 cases and it took 60 days for a case to be analyzed and results reported.
Forensic toxicologists determine if a person was under the influence of drugs or determine what drugs lead to an overdose. They often rely on testing that uses drug panels—targeted lists of commonly abused drugs—which inhibits the discovery of new substances. Their laboratories also face backlogs.
In public health, the goal is to inform people what is in a baggie or pill before they consume it. This community relies heavily on immunoassay fentanyl test strips that can detect the presence of fentanyl (and some of its analogues) only. Fourier transform infrared spectroscopy (FTIR) is also heavily used in this setting but can only detect the major components of mixtures—likely missing the minor, potentially toxic substances.
Overcoming these constraints to get closer to real-time, comprehensive testing is possible, but it will require rethinking the disciplines and increasing their collaboration. Several ongoing efforts, such as is NIST’s RaDAR program, show this is possible. Through this program, I and other chemists provide same-day analysis and comprehensive reporting of drug paraphernalia residues from syringe service programs, overdose scenes or police seizures to public health and public safety entities. This has enabled detection of new substances within a day of a sample being collected. These partnerships have revealed that people who use drugs are often unaware of all the substances present in what they use. Informed use—telling people just what is really in their pills or powder—through the RaDAR program and others like it, has motivated behavioral changes, and better outcomes, in people who use drugs.
To truly unlock comprehensive testing, however, we need to also reconsider our analytical approaches and how we are using the data. While identifying what dangerous substances are in the supply remains vital, knowing its quantity is also important in providing insight into potency and whether bad batches of drugs are on the street. Quantitation has long been completed in biological fluids for toxicological analyses to help determine impairment or cause of death, but it is rarely employed in drug chemistry or public health, when critical information about the actual powder or pill could be obtained. Luckily, the instrumentation and analyses used by toxicologists can be easily adapted and employed in the other two disciplines.
Identifying new substances would be another huge step in unlocking comprehensive testing. Current instruments and methods rely on libraries or databases of known compounds to make identifications, which means it is easy to detect things we know to look for, but difficult to identify new ones. By using machine learning or other algorithms to examine the data produced by these instruments, researchers could identify new substances where no library entry exists. Though early, this is likely only a matter of time before its widespread use in all three disciplines.
While we wait for a mythical low-cost, on-site, rapid technology that can qualitatively and quantitatively identify all chemicals in a drug sample, we need to focus on rethinking the use of the technologies we already have, to comprehensively investigate the drug supply. Modifying methods, promoting data sharing, unifying reporting and emphasizing rapid analysis could go a long way.
Just as we warn people about tainted lettuce or contaminated eye drops, we need to warn them about dangerous adulterants or new drugs in an illicit drug supply already killing hundreds of Americans every day. It is past time to become more proactive in our approach. No longer is it a question of whether there will be a new drug on the street but instead a question of when. And the unfortunate answer is that it is likely already here; we just haven’t found it yet.
This is an opinion and analysis article, and the views expressed by the author or authors are not necessarily those of Scientific American.