Tennessee has been one of the states hardest hit by the national opioid crisis. Efforts to combat it, such as judicious opioid prescribing practices and legislative efforts, have made some Tennesseans more susceptible to alternatives, such as designer drugs, also known as novel psychoactive substances (NPS). These compounds, which are more prevalent and dangerous than ever, mimic the effects of prescription or illicit drugs while avoiding detection by routine testing and circumventing drug regulations.
The way forward includes well-informed testing, which coupled with knowledge of major classes of NPS detected in Tennessee this year, enables the care community to adapt and prepare.
Testing for the presence of substances in biological specimens like urine or saliva offers the only objective measure of an individual’s recent substance use history. Without proper testing, a care plan may not be as effective. However, it is important to understand the limitations of standard testing and the need for enhanced confirmation testing and education about the local supply. Unfortunately, the illicit drug supply evolves rapidly, while conventional testing available to health care providers reacts more slowly.
I spoke with Dr. Lerebours, a family medicine doctor here in Nashville who specializes in addiction. In his experience, testing can often be limited due to a variety of factors, such as window of detection, methodology, and the cross-reactivity of certain substances. The illicit origin of NPS increases the chances of cross-contamination with other substances and often means that patients are unaware of what they have been exposed to. That is why thorough, specific testing is essential. Otherwise, patients are at a greater risk of adverse reactions.
Traditional testing typically utilizes either immunoassay technology at the point of care (POC) or mass spectrometry, performed in a laboratory. Immunoassay technology may detect some classes of designer drugs via cross-reactivity; but it cannot identify the specific compounds or the number of compounds present, which can lead to confusion regarding the source of a positive result. Traditional mass spectrometry typically does not target designer drugs at all.
As a result, relying on standard testing risks missing or misidentifying the drugs in patients’ systems, and therefore risks an incorrect interpretation, diagnosis, and treatment. Enhanced confirmation testing, which is targeted toward designer drugs, provides a more accurate clinical picture and enables providers to implement more informed harm-reduction strategies.
Knowledge of the drugs in local circulation is also crucial. Emergency department providers, local addiction medicine professionals, medical examiners, and forensic laboratories can provide this data; but the potential use of standard testing may not provide the whole picture. This leads to a gap in public health awareness on what NPS to watch out for.
The best known NPS are designer opioids, which are formulated into powder or pressed into tablets to resemble prescription opioids. Fentanyl is the most commonly detected opioid throughout the country because it can be detected by standard tests. However, there has been a recent rise in fentanyl analogs (fentalogs) and non-fentanyl designer opioids such as the benzimidazoles or “nitazenes,” which are more insidious – and possibly more potent – than “plain” fentanyl. Unfortunately, these designer drugs are a present and growing threat nationally and locally.
Last year in Tennessee, Aegis detected three new fentalogs, three new nitazenes, and eight designer benzodiazepines. Detection of each of these compounds requires specific, targeted testing. Testing for one analog or one benzodiazepine will not detect another and can result in false negatives. As NPS evolve, so must testing panels evolve to detect them.
In speaking with our local partners, we found that the lack of awareness around these NPS is due to the lack of comprehensive testing. According to Dr. Lerebours, point-of-care tests (POCTs), common at clinics, often test for only one or a few compounds, or an entire class, like benzodiazepines. This can lead to false negatives, even for traditional benzodiazepines, if a new, unspecified compound is present. Even positive POCT results provide insufficient information. With opioids and compounds like benzodiazepines, when these tests are positive, they don’t specify the parent drug – forcing providers to play a guessing game on the compounds present in their patient’s system.
What other NPS are part of the Tennessee landscape? Some drugs do not fit into the major designer drug classes but are also found in various forms. Xylazine, a veterinary tranquilizer not approved for human use, is progressively being found mixed with fentanyl, where it is believed to prolong the effects of non-medical fentanyl use. While xylazine reduces Central Nervous System (CNS) activity, it is not an opioid. Consequently, it is resistant to naloxone reversal and is increasingly identified in overdose deaths involving illicit opioids. Xylazine is also associated with skin and soft tissue infections, which have led to amputations.
Phenibut and tianeptine have also been detected in Tennessee and are sold over the counter. These are prescription drugs in other countries, so knowledge of their use can be beneficial. Phenibut is taken to relieve anxiety, and tianeptine is an antidepressant but is often used to blunt opioid withdrawal symptoms.
What all of this tells us is that the drug landscape is broader and more dynamic than we can imagine. As drug use trends shift and compounds continue to adapt and grow more dangerous, comprehensive testing and collaboration among providers, public officials, and medical experts are the only ways to accurately reflect the landscape. Awareness of designer drugs and their potential dangers can improve care strategies, reduce the public health risk, and ultimately, save lives.
Dr. Andrew Holt, Pharm.D., is part of the Clinical Team at Aegis Sciences Corporation, a national health care testing lab based in Nashville.