Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism

Addiction Neuroscience, Journal Year: 2024, Volume and Issue: 11, P. 100155 - 100155

Published: May 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.

Language: Английский

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Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: June 16, 2024

Evidence-based practices for reducing opioid-related overdose deaths include education and naloxone distribution, the use of medications treatment opioid disorder, prescription safety. Data are needed on effectiveness a community-engaged intervention to reduce through enhanced uptake these practices.

Language: Английский

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Overdose from Unintentional Fentanyl Use when Intending to Use a Non-opioid Substance: An Analysis of Medically Attended Opioid Overdose Events

Journal of Urban Health, Journal Year: 2024, Volume and Issue: 101(2), P. 245 - 251

Published: April 1, 2024

Language: Английский

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A qualitative study on perceptions and experiences of overdose among people who smoke drugs in Vancouver, British Columbia

Drug and Alcohol Dependence, Journal Year: 2024, Volume and Issue: 258, P. 111275 - 111275

Published: March 29, 2024

Smoking unregulated drugs has increased substantially in British Columbia. Intersecting with the ongoing overdose crisis, drug smoking-related fatalities have correspondingly surged. However, little is known about experiences of among people who smoke accessing toxic supply. This study explores perceptions and drugs.

Language: Английский

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Endogenous opiates and behavior: 2023

Peptides, Journal Year: 2024, Volume and Issue: 179, P. 171268 - 171268

Published: June 28, 2024

Language: Английский

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The Rise of Fentanyl: Molecular Aspects and Forensic Investigations

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 444 - 444

Published: Jan. 7, 2025

Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, high potency, low cost, accessibility have also made it significant drug of abuse, contributing to the global epidemic. This review aims provide an in-depth analysis fentanyl's medical applications, pharmacokinetics, metabolism, pharmacogenetics while examining adverse forensic implications. Special attention given misuse, polydrug interactions, challenges determining cause death fentanyl-related fatalities. misuse has escalated dramatically, driven by substitution heroin availability through online platforms, including dark web. Polydrug use, where fentanyl combined with substances like xylazine, alcohol, benzodiazepines, or cocaine, exacerbates toxicity increases risk fatal outcomes. undergoes rapid distribution, metabolism CYP3A4 into inactive metabolites, renal excretion. Genetic polymorphisms CYP3A4, OPRM1, ABCB1 significantly influence individual responses fentanyl, affecting efficacy potential toxicity. Fentanyl's side include respiratory depression, cardiac arrhythmias, gastrointestinal dysfunction, neurocognitive impairments. Chronic disrupts brain function, contributes mental health disorders, poses risks younger older populations alike. Fentanyl-related deaths require comprehensive investigations, judicial inspections, autopsies, toxicological analyses. Additionally, co-administration xylazine presents distinct scientific community. Histological immunohistochemical studies are essential understanding organ-specific damage, pharmacogenetic testing can identify susceptibilities. The growing prevalence abuse highlights need robust protocols, advanced research variability, strategies mitigate misuse. International collaboration, public education, harm reduction measures critical addressing crisis effectively.

Language: Английский

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“We’ve lost a lot of lives:” The Impact of the Closure of North America’s Busiest Supervised Consumption Site on People Who Use Substances and the Organizations that Work with Them

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Background Supervised Consumption Sites (SCSs) are an evidence-based harm reduction strategy to reduce the risk of fatal drug poisonings. However, this approach has faced political opposition in Canada, resulting closures SCSs some provinces. Our study aims add understanding impact SCS by exploring perspectives both people who use substances (PWUS) and staff members organizations that continue provide services. explores aftermath closure what was once North America’s busiest SCS, located Lethbridge, Alberta, offering a contextualized exploration regressive policies. Methods To better understand closure, our adopts descriptive qualitative design explore novel phenomenon within unique context Alberta. We conducted 27 interviews with PWUS 10 Staff Members harm-reduction chose reflexive thematic analysis (TA), which allows for critical realist contextual data analysis. Results developed three themes based on first theme speaks harms Next, second highlights participants motivations behind ARCHES closure. last how navigate approaches while responding worsening poisoning crisis. Conclusions continued need expand services ongoing advocacy reverse policy decisions.

Language: Английский

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Stimulant-involved overdose deaths: Constructing dynamic hypotheses

International Journal of Drug Policy, Journal Year: 2025, Volume and Issue: 136, P. 104702 - 104702

Published: Jan. 26, 2025

Language: Английский

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The prevalence of fentanyl in New York City’s unregulated drug supply as measured through drug checking offered at syringe service programs

Drug and Alcohol Dependence, Journal Year: 2025, Volume and Issue: unknown, P. 112578 - 112578

Published: Jan. 1, 2025

Language: Английский

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Fentanyl and Fentanyl Analog Screening Using ASAP‐MS With LiveID Confirmation

Rapid Communications in Mass Spectrometry, Journal Year: 2025, Volume and Issue: 39(9)

Published: Jan. 28, 2025

ABSTRACT Rationale Fentanyl and fentanyl analogs continue to pose a serious threat the public health. The vast number of emerging on black‐market call for optimized analytical methods detection, analysis, characterization these extremely dangerous drugs. Methods Atmospheric pressure solids analysis probe (ASAP) mass spectrometry was used rapid 250 synthetic opioid standards, including 211 analogs, 32 non‐fentanyl related opioids, 8 precursors. Four cone voltages (5, 15, 35 50 V) were obtain fingerprint data each reference sample. Results generated processed spectra opioids analyzed utilized create an ASAP + database that contains largest compendium analogs. built library integrated into LiveID software, enabling real‐time analyte identification. efficacy software's ability identify in sample utilizing spectral tested by analyzing five blind four reaction mixtures. correct identity nine samples all within top three ranked matches. Conclusion We demonstrate how RADIAN ASAP, alongside recognition can be as presumptive tool screening question, making it promising alternative some most commonly techniques.

Language: Английский

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