Drug and Alcohol Dependence, Год журнала: 2024, Номер 264, С. 112450 - 112450
Опубликована: Сен. 16, 2024
Язык: Английский
Addiction Neuroscience, Год журнала: 2024, Номер 11, С. 100155 - 100155
Опубликована: Май 3, 2024
Xylazine is in the unregulated drug supply at increasing rates, usually combined with fentanyl, necessitating understanding of its pharmacology. Despite commentary from politicians, and public health officials, it unknown how xylazine impacts naloxone efficacy, and. few studies have examined alone. Here, we examine impact alone combination fentanyl on several behaviors mice. Surprisingly, precipitates withdrawal fentanyl/xylazine coadministration, enhanced sensitivity females. Further, a full agonist kappa opioid receptors, potential mechanism for sensitivity. Finally, demonstrate surprising effects to antagonism, which are relevant considerations. These data address an ongoing crisis will help inform critical policy healthcare decisions. We present new insights into pharmacology immediate implications clinical practice frontline health.
Язык: Английский
Процитировано
16
Current Pain and Headache Reports, Год журнала: 2024, Номер 28(5), С. 417 - 426
Опубликована: Март 20, 2024
The opioid epidemic has been responsible for significant morbidity and mortality in the USA worldwide. As a result, it is essential to recognize threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as drug adulterant shown impact overdose rates drastically. In this regard, Drug Enforcement Agency recently released public safety alert announcing new of called xylazine. Xylazine powerful animal sedative with different mechanism action compared illicit opioids such heroin fentanyl. typically injected intravenously via syringe, often combination multiple other drugs. One most common drugs, xylazine, taken fentanyl, users describing xylazine prolonging euphoric sensation produced by
Язык: Английский
Процитировано
15
Pharmacology Biochemistry and Behavior, Год журнала: 2024, Номер 243, С. 173836 - 173836
Опубликована: Июль 26, 2024
Preclinical models of addictive drugs have been developed for decades to model aspects the clinical experience in substance use disorders (SUDs). These include passive exposure as well volitional intake across and utilized also measure withdrawal symptomatology potential neurobehavioral mechanisms underlying relapse drug seeking or taking. There are a number Food Drug Administration (FDA)-approved medications SUDs, however, many demonstrate low efficacy sex differences, we note gaps continuum care certain experiences individuals who drugs. In this review, provide comprehensive update on both frequently novel behavioral addiction with focus translational value highlight need preclinical research follow epidemiological trends patterns stay abreast treatment needs. We then areas which could be improved enhance development pipeline through efforts translation models. Next, describe neuroscience that can leveraged identify biological focusing specifically advances brain transcriptomics approaches screening identification targets. Together, confluence review demonstrates careful selection methodological parameters better approximate combined cutting edge techniques advance SUDs.
Язык: Английский
Процитировано
6
Neuropharmacology, Год журнала: 2023, Номер 245, С. 109816 - 109816
Опубликована: Дек. 20, 2023
The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. health impacts of xylazine emerging raised alarm regarding public threat, warranting research on fentanyl's behavioral effects. No prior studies have evaluated effects consumption at various unit doses, demand, or withdrawal compared Food and Drug Administration-approved medication, lofexidine (Lucemyra®). This is important because are both adrenergic α2a (A2aR) agonists, however, not noted adulterant. Here we combined with self-administered doses male female rats body weight, acute withdrawal. Consumption alone increased saline. Xylazine but downward number suppressed demand intensity control group. Further, + reduced signs immediately following SA, by 12 h only co-exposed Weight loss occurred throughout SA regardless group, although group lost significantly more weight during first 24 than other two groups. Severity was also correlated severity somatic Together, these results suggest that may be indicator from xylazine/fentanyl combination, further translational evaluation.
Язык: Английский
Процитировано
10
Policy Politics & Nursing Practice, Год журнала: 2024, Номер 25(4), С. 241 - 253
Опубликована: Авг. 7, 2024
Xylazine, a veterinary sedative, has emerged as concerning element in the landscape of substance use United States. This integrative review synthesizes evidence from systematic examination 14 selected studies conducted between 2008 and 2023. The primary objective is to comprehensively understand epidemiology prevalence xylazine use, particularly its involvement drug-related deaths, regional variations, national impact, co-occurrence with opioids, challenges associated detection intervention. results underscore stark disparities prevalence. West Virginia Miami-Dade County have experienced alarming surges xylazine-involved deaths. Nationally, influence extends beyond boundaries, predominantly affecting white males Northeast. especially fentanyl heroin, significantly amplifies risks fatal overdoses. Detecting presents formidable due frequent presence alongside other substances, necessitating enhanced surveillance more effective methods. User perspectives emerge pivotal, emphasizing importance user-informed harm reduction strategies. In conclusion, this significant policy implications. Tailored, region-specific strategies are imperative address diverse use. A nationwide response indispensable, prioritizing initiatives, methods, active user engagement. multifaceted nature issue requires comprehensive approaches mitigate profound effectively. Policymakers urged consider opioids when crafting targeted interventions. Immediate, vital evolving
Язык: Английский
Процитировано
4
Behavioural Pharmacology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 23, 2025
In recent years, the recreational use of xylazine has increased dramatically in USA. Although been used as an anesthetic veterinary medicine for decades, little is known about its behavioral effects. We took advantage planarian’s innate negative phototaxis, reliable movement from light side to dark a Petri dish, explore organism’s suitability animal model investigating preclinical pharmacology xylazine. two experiments, we tested effects several doses on locomotion by recording latency transition into opaque area. Xylazine disrupted dose-dependent fashion. Larger first produced period hyperkinesia without forward motion. This was followed sedation. Physical stimulation sedation and evoked resumption locomotion. Data outside anesthesia are limited; therefore, current study adds relatively small literature
Язык: Английский
Процитировано
0
Journal of Pharmacology and Experimental Therapeutics, Год журнала: 2025, Номер 392(4), С. 103397 - 103397
Опубликована: Фев. 5, 2025
A recent twist to the ongoing tragedy of opioid epidemic is adulteration fentanyl with veterinary tranquilizer xylazine, an α2-adrenoreceptor agonist. Unfortunately, our knowledge how and xylazine interact pharmacologically in different behavioral assays limited. We examined alone, 4 antagonists, multiple dose ratio combinations using a 52.5 °C hot-plate antinociception assay Swiss-Webster male female mice. Both produced full, dose-dependent increases antinociception. In antagonism studies, naltrexone blocked whereas yohimbine selective antagonist, idazoxan, antinociceptive effects xylazine. Naltrexone failed inhibit increased or decreased potency depending on dose. Haloperidol, D2/σ1 significantly shifted left. Overall, combining alter although when proportion was higher, less potent than alone. Either alone block 2.5X combination. However, either idazoxan combination suggesting that both noradrenergic receptors appear involved this conclusion, combined are dependent proportions coadministered antagonists may be required adulterated SIGNIFICANCE STATEMENT: Combinations agonist currently illicit drug market. The experiments described here examine pharmacology these drugs model mice better understand underlying receptor mechanisms for were predominantly simple agonism.
Язык: Английский
Процитировано
0
Addiction Neuroscience, Год журнала: 2025, Номер unknown, С. 100204 - 100204
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Journal of Pharmacology and Experimental Therapeutics, Год журнала: 2025, Номер unknown, С. 103616 - 103616
Опубликована: Май 1, 2025
Язык: Английский
Процитировано
0
Drug and Alcohol Dependence, Год журнала: 2024, Номер 258, С. 111282 - 111282
Опубликована: Апрель 2, 2024
Язык: Английский
Процитировано
2