Search Results (5)

Background/Objectives: The recreational use of fentanyl (FT) combined with xylazine (XZ), known as “tranq-dope,” poses a growing public health threat due to its high toxicity and mortality. This study evaluated the effectiveness of naloxone (NX), its lipophilic prodrug NX90, and their combinations with the mixed κ-agonist/µ-antagonist nalbuphine (NB) in reversing overdose and restoring respiratory function in a rat model. Methods: Male and female Wistar rats received intramuscular FT (0.104 mg/kg) + XZ (1 mg/kg) to induce overdose, followed by intranasal administration of NX, NX90, or combinations with NB. Physiological parameters, reflex recovery, time to overdose, and reversal outcomes were assessed during individualized clinical monitoring. Results: At the low FT dose (0.052 mg/kg), adding XZ (1 mg/kg) shortened time to overdose by ~2600 s compared with FT alone, whereas onset times were similar at medium and high FT doses. In the dose-finding cohort, FT + XZ co-administration was associated with a higher respiratory rate than FT alone at the highest fentanyl dose tested, an exploratory finding warranting confirmation in larger studies. Most interventions did not significantly shorten time to reversal; however, NX + NB (females) and NX90 + NB (both sexes) showed shorter reversal times than NX alone. However, respiratory rate at reversal was significantly improved with NX + NB, ½NX90 + NB and NX90 + NB (90 ± 6, 86 ± 5 and 92 ± 5 breaths/min) compared with naloxone alone (80 ± 6 breaths/min). Interventions containing nalbuphine (κ-agonist/µ-antagonist) yielded higher RR and HR at reversal than NX alone, consistent with an interpretive framework in which κ–µ opioid balance may influence observed physiological recovery patterns. Conclusions: Comparable or improved reversal outcomes could be achieved using half-doses of NX or NX90 with NB—potentially reducing the total dose of naloxone and mitigating the risk of precipitated withdrawal in individuals with opioid use disorder. Full article

Xylazine (XYL), an FDA-approved veterinary tranquilizer, is being abused both as an opioid adulterant in a street-drug known as “Tranq-dope” and as a date rape drug. Given its now nearly ubiquitous use with fentanyl and fentanyl derivatives across the globe, XYL has become a primary target for researchers seeking to develop portable and cost-effective sensors for its detection. Electrochemical sensors based on the oxidation of XYL, while useful, have limitations due to certain interferents and inherent electrode fouling that render the approach less reliable, especially in certain sample matrices. In this work, modified electrode platforms incorporating layers of multi-walled carbon nanotubes for sensitivity along with semi-permeable polyurethane (PU) layers and host–guest chemistry using β-cyclodextrin for selectivity are deployed for XYL detection using complementary adsorptive cathodic stripping analysis. The modified electrode sensors are optimized to minimize high potentials and maintain fouling resistant capabilities and investigated to better understand the function of the PU layer. The use of adsorptive cathodic stripping differential pulse voltammetry indirectly indicates the presence and concentration of XYL within complex sample media (beverages and synthetic urine). When used in this manner, the modified electrodes exhibited an overall average sensitivity of ~35 (±9) nA/μM toward XYL with a limit of quantification of <10 ppm, while also offering adaptability for the analysis of XYL in different types of samples. By expanding the capability of these XYL sensors, this study represents another facet of tool development for use by medical professionals, first-responders, forensic investigators, and drug-users to limit exposure and help stem the dangerous and illegal use of XYL. Full article

Background/Objectives: Philadelphia has experienced a surge in illicit fentanyl adulterated with alpha-2 agonist sedatives. Initially, xylazine (“tranq”) was the predominant adulterant, and a novel multimodal withdrawal protocol was effective at mitigating symptoms. However, since mid-2024, medetomidine—a more potent sedative—has largely supplanted xylazine. Clinicians have reported more severe, treatment-resistant opioid withdrawal during this transition. To assess whether a previously effective withdrawal management protocol retained efficacy after the emergence of medetomidine as the primary fentanyl adulterant in a community. Methods: We conducted a retrospective cohort study of patients receiving protocol-based opioid withdrawal treatment at two emergency departments in Philadelphia between September 2022 and April 2025. Patients were divided into the xylazine era (September 2022–July 2024) and medetomidine era (August 2024–April 2025). The primary outcome was a change in Clinical Opioid Withdrawal Scale (COWS) score from pre- to post-treatment. Secondary outcomes included rates of discharge against medical advice (AMA) and ICU admission, as well as the impact of a revised treatment protocol. Results: Among 1269 encounters with full data, 616 occurred during the xylazine era and 770 during the medetomidine era. Median COWS reduction was greater in the xylazine group (−9.0 vs. −4.0 points, p < 0.001), with more patients achieving symptom relief (COWS ≤ 4: 65.6% vs. 14.2%, p < 0.001). ICU admission occurred in 8.5% of xylazine era patients and 16.8% of medetomidine era patients (p < 0.001). Rates of AMA were higher during the medetomidine era as well (6.5% vs. 3.6%) (p = 0.038). Revision of treatment protocols showed promise. Conclusions: The protocol was significantly less effective during the medetomidine era, though a protocol change may be helping. Findings highlight the need to adapt withdrawal treatment protocols in response to changes in the illicit drug supply. Full article

Xylazine, commonly called “tranq” or “sleep cut”, is a strong α2-adrenergic agonist used in veterinary practice as a sedative, analgesic, and muscle-relaxing agent. It has never been approved by the Food and Drug Administration for human use, but its use by people is on the rise. In the last decades, due to its low cost and ease of availability, it has often been illicitly used due to its abuse potential as a drug for attempted sexual assault and intended poisoning. In addition, xylazine’s presence in the human body has also been related to domestic accidental events. Generally, it is combined with multiple other drugs, typically by intravenous injection, potentiating the doping effects. Xylazine’s mechanism of action is different from that of other illicit opioids, such as heroin and fentanyl, and it has no known antidote approved for use in humans. The combination with fentanyl prolongs the euphoric sensation and may heighten the risk of fatal overdose. Furthermore, it may cause adverse effects, including central nervous system (CNS) and respiratory depression, bradycardia, hypotension, and even death. Recent reports of xylazine misuse have risen alarmingly and describe people who become “zombies” because of the drug’s harmful effects on the human body, including serious wound formation that could even lead to limb amputation. This paper is an extensive review of the existing literature about xylazine and specifically deals with the chemistry, pharmacokinetics, pharmacodynamic, and toxicological aspects of this compound, highlighting the most recent studies. Full article

As the opioid crisis continues to wreak havoc on a global scale, it is increasingly critical to develop methodologies to detect the most dangerous drugs such as fentanyl and its derivatives, which have orders of magnitude higher potency than morphine. The scientific challenge for chemical detection of fentanyl and its derivatives is complicated by both the constantly increasing synthetic variations of the drug as well as the expanded use of adulterants. One tragically consequential example is the nocuous street drug known as “Tranq”, which combines fentanyl or a fentanyl derivative with the veterinary sedative Rompun^®, chemically identified as xylazine (XYL). This pervasive street cocktail is exacerbating the already staggering number of fentanyl-related deaths as its acute toxicity poses a danger to medical first-responders and complicates their initial assessment and treatment options for overdose victims. Given the widespread use of XYL as an adulterant, an electrochemical XYL sensor capable of on-site operation by non-experts as a fast-screening tool is a notable goal. This work presents a voltammetry-based sensor featuring carbon electrodes modified with carboxylic-acid functionalized multi-walled carbon nanotubes layered with cyclodextrin and polyurethane membranes for sensitivity and selectivity enhancements. The sensor has critical and robust fouling resistance while providing sensitivity at 950 μA/mM∙cm², a low limit of detection (~5 ppm), and the ability to detect XYL in the presence of fentanyl and/or other non-fentanyl stimulants like cocaine. The demonstrated sensor can be applied to promote public health with its ability to detect and indicate XYL in the presence of opioids, serving to protect drug-users, first responders, medical examiners, and on-site forensic investigators from exposure to these dangerous mixtures. Full article