Public Alerts

Lidocaine, like the other local anesthetics (LA) discussed in this report, is a synthetic compound useful in medical procedures as an anesthetic, usually available as an over-the-counter (OTC) topical cream, transdermal patch, or injectable solution administered in a medical procedure. The numbing sensation is caused by the blockade of neuronal sodium channels, thus reducing the transmission of pain signals. Because local anesthetics produce a numbing sensation, they may be added in minor amounts to reduce the discomfort involved with injecting or snorting drugs. While lidocaine is the LA most frequently combined with illicit drugs, other LA compounds that could be added to drug samples include benzocaine, procaine, tetracaine, mepivacaine, and bupivacaine.
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Diphenhydramine (e.g. Benadryl) is an over-the-counter first generation antihistamine approved for allergy treatment by the United States Food and Drug Administration (FDA) in 1946. Diphenhydramine can also be used for its sedative and antiemetic effects. It acts as an antagonist for the histamine 1 (H1) receptor, reversing the effects of histamine in the body and reducing allergic reactions. Due to its ability to cross the blood brain barrier and antagonize the H1 receptors in the central nervous system (CNS), diphenhydramine can cause drowsiness and suppress the medullary cough center. Diphenhydramine also acts as a competitive antagonist for muscarine acetylcholine receptors and as a sodium channel blocker, and higher doses may lead to cardiotoxic effects. It is metabolized in the liver to desmethyldiphenhydramine and diphenylmethoxyacetic acid.
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Phenylbutazone (“Bute”, Phenylcare®) has been identified as an adulterant in illicit drug material. In a review of case data from NMS Labs from 2016-2021, 116 seized drug samples  from Pennsylvania were identified as containing phenylbutazone. This represents a small percentage of total samples analyzed during the time frame. Xylazine, which is now a national concern, first emerged in the northeast (principally Pennsylvania) before spreading across the United States. As phenylbutazone has been gaining prominence in Pennsylvania over a five-year period, the possibility exists that it too can spread nationwide. This adulterant was most frequently observed in samples containing heroin, fentanyl and/or fentanyl derivatives. In addition to illicit drug samples, there have been reports in the literature of adulteration of herbal medicines and supplements with phenylbutazone and self-medication with phenylbutazone prescribed by veterinarians. The serious adverse effects of phenylbutazone can include gastrointestinal bleeding, liver and kidney damage, and blood disorders.
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A partnership between the Center for Forensic Science Research and Education (CFSRE) and the Drug Enforcement Administration (DEA) Intelligence Group at the Pittsburgh District Office was established to evaluate vape products that were recovered from high schools. The main objective was to differentiate nicotine from cannabis vape products (or others) through comprehensive drug testing, in addition to determining if potentially harmful substances were present and if there was any evidence of mixing, substitution, and/or adulteration with other drugs or substances. 
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N-Desethyl isotonitazene is a new synthetic opioid bearing structural resemblance to isotonitazene and recently emergent nitazene analogues. N-Desethyl isotonitazene is dissimilar in chemical structure to fentanyl, the synthetic opioid most commonly encountered, but this subclass of new opioids has been proliferating in the wake of the scheduling of fentanyl analogues. N-Desethyl isotonitazene is a known metabolite of isotonitazene; however, it has now emerged as a primary drug in its own right. Most nitazene analogues encountered retain opioid receptor activity and potency similar to or greater than fentanyl. In vitro pharmacological data show that N-desethyl isotonitazene is an active opioid agonist and is approximately 20x more potent than fentanyl. In December 2022, N-desethyl isotonitazene was first reported by NPS Discovery (Florida); however, first identifications were observed as early as September 2022. To date, seven drug material samples (“dope” powders) collected from the Philadelphia drug supply have tested positive for N-desethyl isotonitazene. In December 2022, the Philadelphia Department of Public Health issued an alert regarding the discovery of this new nitazene analogue in the city’s drug supply. The toxicity of N-desethyl isotonitazene has not been examined or reported but recent association with overdoses among people who use drugs leads professionals to believe this synthetic opioid has the potential to cause harm and is of high public health concern.
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Quinine and its naturally occurring stereoisomer quinidine are natural alkaloids found in the bark of the cinchona tree, originally from South America. Today, quinine and quinidine are individually synthesized for pharmaceutical and medical purposes.  Both are effective antimalarial drugs; however, quinidine is also prescribed as a class 1a antiarrhythmic medication. Quinine and quinidine both have a similar mechanism of action as antimalarial drugs. They interfere with the malaria parasite’s ability to digest hemoglobin, with quinidine being reportedly more effective in doing so. Quinine and quinidine also block sodium and potassium channels to stabilize heart rhythm, but only quinidine is prescribed for this purpose. The drugs are mainly metabolized via CYP2D6 to an inactive 3-hydroxyquinine and 3-hydroxyquinidine metabolite, respectively. Trade names for quinine include, Qualaquin® and for quinidine include Cardioquin®, Cin-Quin®, and Quinidex®. Quinine is also present in some food and beverages such as teas, Bitter Lemon, and Tonic Water. Laboratory tests may not distinguish between quinine and quinidine, and their presence may be reported non-specifically as undifferentiated quinine/quinidine.
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Bromazolam first emerged in the recreational drug supply in 2016 (Europe) and 2019 (United States). Bromazolam was first synthesized during medicinal drug development in the 1970s but never approved for therapeutic use in the United States. Bromazolam is the brominated counterpart to the chlorinated drug alprazolam. Bromazolam has been linked to adverse events resulting in hospitalization and death. Bromazolam is commonly reported in combination with other drugs, including the opioid fentanyl. To date, bromazolam has been identified in more than 250 toxicology cases submitted to NMS Labs, including both antemortem and postmortem investigations. Bromazolam has been identified in more than 190 toxicology samples tested at the Center for Forensic Science Research and Education (CFSRE), displaying an increase in positivity from 1% in Q1 2021 to 13% in Q2 2022. More significantly, co-detections with fentanyl have increased in recent months to more than 75% for bromazolam positive samples. Bromazolam has also been confirmed in counterfeit benzodiazepine preparations at the CFSRE.
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In 2020 and 2021, the substituted cathinone eutylone was the most commonly encountered synthetic stimulant to appear in forensic casework, despite the drug being considered federally scheduled as an isomer of pentylone since March 2017 according to the U.S. Drug Enforcement Administration (DEA). In September 2021, eutylone was recommended for international control. It is this notice that likely created a shift in the NPS drug market, which would later be noted by declining eutylone positivity and increasing N,N-dimethylpentylone positivity. N,N-Dimethylpentylone was first identified in toxicology samples in the U.S. in Q3 2021, marking the initial insurgence of this drug into the supply and the beginning of its proliferation. To date, N,N-dimethylpentylone has been identified in 32 toxicology cases, including antemortem and postmortem investigations, in addition to drug material cases. N,N-Dimethylpentylone is not explicitly scheduled in the U.S.; however, it could be considered an isomer of N-ethyl pentylone (Schedule I). Of note, pentylone is a metabolite of N,N-dimethylpentylone.
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Etodesnitazene is a new synthetic opioid bearing structural resemblance to etonitazene, a synthetic opioid that is nationally and internationally controlled. Etodesnitazene is dissimilar in structure to synthetic opioids typically encountered in forensic casework (e.g., fentanyl, heroin); however, several analogues of this series (known as “nitazenes”) have recently emerged in several countries around the world. In vitro pharmacological data show that etodesnitazene is an active opioid agonist which is approximately four times less potent than fentanyl (a common phenomenon for analogues missing the 5-nitro group) but approximately six times more potent than morphine. Etodesnitazene was first reported by NPS Discovery in February 2021 following initial detection in a toxicology case. To date, ten blood and/or urine specimens associated with postmortem death investigations or clinical intoxications in the United States and Canada were confirmed to contain etodesnitazene. Identifications of etodesnitazene have also been reported from organizations in Europe. The toxicity of etodesnitazene has not been examined or reported but recent association with death among people who use drugs leads professionals to believe this synthetic opioid retains the potential to cause harm and is of public health concern.
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Protonitazene is a new, potent synthetic opioid bearing structural resemblance to etonitazene, a synthetic opioid that is nationally and internationally controlled. Protonitazene is dissimilar in structure to synthetic opioids typically encountered in forensic casework (e.g., fentanyl, heroin); however, protonitazene is a structural isomer of isotonitazene, requiring increased analytical specificity during toxicological analysis. In vitro pharmacological data suggest that this new opioid exhibits potency similar to other recently emergent “nitazene” opioids, and is approximately three times more potent than fentanyl. Protonitazene was first reported by NPS Discovery in May 2021 following initial detection in a toxicology case. To date, nine blood specimens associated with postmortem death investigations in the U.S. were confirmed to contain protonitazene; however, at least six additional cases have been discovered through toxicological surveillance by NPS Discovery as of December 2021. Identifications of protonitazene have also been reported from organizations in Europe. The toxicity of protonitazene has not been examined or reported but recent association with death among people who use drugs leads professionals to believe this synthetic opioid retains the potential to cause widespread harm and is of public health concern.
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