Pharmacokinetics and Pharmacodynamics of Psychoactive Substances: Clinical and Forensic Aspects 2023

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 1595

Special Issue Editor

1. TOXRUN – Toxicology Research Unit, University Institute of Health Sciences, Advanced Polytechnic and University Cooperative (CESPU), CRL, 4585-116 Gandra, Portugal
2. Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
3. UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
4. MTG Research and Development Lab, 4200-604 Porto, Portugal
Interests: real-world evidence; implementation science; toxicology; forensic sciences; psychoactive substances; drugs; biomedical research; scientometrics; scientific medical writing; pedagogical Innovation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue aims to cover the chemical structure, available products, pharmacokinetics, pharmacodynamics, metabolomics, clinical manifestations, diagnostics, and treatment of acute intoxications related to psychoactive substances in order to highlight their impact on public health. To better understand the clinical and forensic effects, pharmacokinetics should be explored to find active and inactive metabolites and other biomarkers. Indeed, polymorphisms in genes encoding enzymes (e.g., CPY2B6) involved in metabolism or target receptors may influence both drug efficacy and toxicity. Besides genetics, the extensive metabolism by P450 can lead to important interactions when drugs are taken concomitantly. The identification of additional metabolites is also needed during drug development and for clinical and forensic toxicology, where specific metabolites are used to confirm xenobiotic exposure as potential biomarkers.

Prof. Dr. Ricardo Jorge Dinis-Oliveira
Guest Editor

Manuscript Submission Information

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Keywords

  • psychoactive substances
  • toxicokinetics
  • toxicodynamics
  • toxicological analysis
  • interpretation of toxicological reports
  • antemortem toxicology
  • postmortem toxicology
  • clinical and forensic issues

Published Papers (1 paper)

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Research

17 pages, 7670 KiB  
Article
Effect of Repeated Administration of ɣ-Valerolactone (GVL) and GHB in the Mouse: Neuroadaptive Changes of the GHB and GABAergic System
Pharmaceuticals 2023, 16(9), 1225; https://doi.org/10.3390/ph16091225 - 30 Aug 2023
Viewed by 1180
Abstract
Background: Gamma-hydroxybutyric acid (GHB) at low dosages has anxiolytic effects and promotes REM sleep and low-wave deep sleep. In the U.S., the legal form of GHB is prescribed to adults suffering from narcolepsy-associated cataplexy; the sodium salt of GHB is reserved for alcohol-addiction [...] Read more.
Background: Gamma-hydroxybutyric acid (GHB) at low dosages has anxiolytic effects and promotes REM sleep and low-wave deep sleep. In the U.S., the legal form of GHB is prescribed to adults suffering from narcolepsy-associated cataplexy; the sodium salt of GHB is reserved for alcohol-addiction treatment. GHB is also a molecule of abuse and recreational use, it is a controlled substance in several countries, so gamma-valerolactone (GVL) has frequently been used as a legal substitute for it. GHB’s abuse profile is most likely attributable to its anxiolytic, hypnotic, and euphoric properties, as well as its widespread availability and inexpensive/low cost on the illicit market. Methods: Our study is focused on evaluating the potential effects on the mouse brain after repeated/prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) through behavioral study and immunohistochemical analysis using the markers tetraspanin 17 (TSPAN17), aldehyde dehydrogenase 5 (ALDH5A1), Gamma-aminobutyric acid type A receptor (GABA-A), and Gamma-aminobutyric acid type B receptor (GABA-B). Results: Our findings revealed that prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) can have effects on a component of the mouse brain, the intensity of which can be assessed using immunohistochemistry. The findings revealed that long-term GHB administration causes a significant plastic alteration of the GHB signaling system, with downregulation of the putative binding site (TSPAN17) and overexpression of ALDH5A1, especially in hippocampal neurons. Our findings further revealed that GABA-A and GABA-B receptors are downregulated in these brain locations, resulting in a greater decrease in GABA-B expression. Conclusions: The goal of this study, from the point of view of forensic pathology, is to provide a new methodological strategy for better understanding the properties of this controversial substance, which could help us better grasp the unknown mechanism underlying its abuse profile. Full article
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