Public Alerts

N-Pyrrolidino protonitazene is a new synthetic opioid and the latest to emerge among the nitazene analogue (or 2-benzyl benzimidazole) subclass. N-Pyrrolidino protonitazene bears structural resemblance to both protonitazene and N-pyrrolidino etonitazene, two previously encountered nitazene analogues. N-Pyrrolidino protonitazene is dissimilar in chemical structure to fentanyl. New synthetic opioids, namely the nitazene analogues, have sustained proliferation following the 2018 scheduling of fentanyl related substances. Most nitazene analogues encountered among the recreational drug supply retain opioid receptor activity and exhibit potency similar to or greater than that of fentanyl. Recently acquired in vitro pharmacological data show that N-pyrrolidino protonitazene is an active opioid with potency approximately 25 times greater than that of fentanyl [source: L. De Vrieze and C. Stove, Ghent University].

To date in August 2023, N-pyrrolidino protonitazene has been confirmed in 20 forensic toxicology cases, all of which were medicolegal death investigations. N-Pyrrolidino protonitazene was first reported by CFSRE’s NPS Discovery in January 2023; however, the date of first sample collection was as early as December 2022. Cases originated from seven states across many regions within the United States, as well as the United Kingdom. Decedent age ranged from mid-20s to mid-70s (mean: 45 years, median: 44 years). Quantitative blood concentrations for N-pyrrolidino protonitazene ranged from 0.1 to 55 ng/mL (mean: 6.9 ng/mL, median: 1.1 ng/mL). The toxicity of N-pyrrolidino protonitazene has not been examined or reported but recent association with overdoses among people who use drugs leads professionals to believe that this synthetic opioid has the potential to cause harm and is of high public health concern globally.

DOWNLOAD THE ALERT

Captagon®, the trade name for fenethylline, an amphetamine prodrug, was originally developed by a German company in 1961 as a psychostimulant and eventually used in the treatment of narcolepsy and attention deficit disorder. Because of its side effects, fenethylline became a Schedule I controlled substance in the United States in 1981, was scheduled internationally in 1986, and its licit manufacture ceased. Most of the remaining stock of Captagon® was destroyed, but some was exported to the Middle East, where it became popular as an illicit stimulant. Once the original supply ran out and fenethylline was no longer available, counterfeit captagon tablets bearing the same monogramming of two offset stylized “C’s” (photo), but containing amphetamine in place of fenethylline began to appear. Today, these tablets also contain a variety of adulterants as discussed below. Counterfeit captagon tablets containing amphetamine are now the major drug used illicitly in the Middle East, where they are predominantly manufactured, although their distribution has now spread to parts of Europe. Although there is illicit demand for amphetamine-type substances (ATS) in the US, as of August 2023, there is no evidence of widespread presence of counterfeit amphetamine-containing captagon tablets in the US. CFSRE and the Colombo Plan encourage vigilance for the emergence of these characteristic counterfeit dosage forms in the US drug supply and would encourage any investigators or laboratories who encounter them to notify us at This email address is being protected from spambots. You need JavaScript enabled to view it..
DOWNLOAD THE ALERT

Quetiapine is an atypical antipsychotic agent that is FDA approved for the treatment of schizophrenia, acute manic episodes, and major depressive disorder. The drug also has several off-label indications, such as generalized anxiety disorder, insomnia, and chronic PTSD. Daily doses in adults usually range from 150 to 800 mg, but higher doses are utilized with QT interval monitoring. Somnolence, dizziness, and orthostatic hypotension are common adverse effects. QTc interval prolongation is associated with torsade de pointes, a potentially lethal dysrhythmia.
DOWNLOAD THE ALERT

In utero drug exposure is a significant public health threat to the well-being and normal development of the neonate. Recently, testing of umbilical cord tissue (UCT) has been employed to measure illicit drug exposure. UCT testing is a well-established method which uses a segment of the newborn's cord collected at the time of delivery. UCT shares a detection window similar to that of meconium, as drugs consumed by the mother during the third trimester may be retained. The in utero effects of illicit drug adulterants and cutting agents have not been well studied in humans, nor has their presence been demonstrated to be an effective means for assessing adverse health effects in the neonate.
DOWNLOAD THE ALERT

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.
DOWNLOAD THE ALERT

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.
DOWNLOAD THE ALERT

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.
DOWNLOAD THE ALERT

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. 
DOWNLOAD THIS REPORT

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.
DOWNLOAD THE ALERT

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.
Download the Alert