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Biomolecules
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Molecular and Toxicological Profiling of Drugs of Abuse—in Honor of...
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Molecular and Toxicological Profiling of Drugs of Abuse—in Honor of Professor Félix Carvalho

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 3206

Special Issue Editors

Dr. João Pedro Silva

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Guest Editor
UCIBIO, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Interests: molecular toxicology; developmental neurotoxicology; new psychoactive substances; cannabinoids; oxidative stress
Special Issues, Collections and Topics in MDPI journals
Dr. Vera Marisa Costa

E-Mail Website
Guest Editor
UCIBIO, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Interests: cardiotoxicity; cardio-oncology; chemobrain; clinical toxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue that we have launched in honor of Prof. Félix Carvalho for his lifelong scientific, social and educational contributions to the field of drugs of abuse. He is a Full Professor in Toxicology and the former President of the Federation of European Toxicologists & European Societies of Toxicology (EUROTOX), who has dedicated over 25 years of his career to unraveling the toxicological profiling of substances of abuse, assessing the mechanistic signatures of pharmacologically active drugs. His expertise in mechanistic toxicology has directly resulted in the development of antidotes and therapeutics, repurposed from already existing drugs, against toxic agents or disorders with high public health impact worldwide due to their high morbidity and mortality levels. He is a scientific advisor on several national/international boards of regulatory agencies, as well as a Member of the Scientific Committee of the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), External Expert of the European Medicines Agency (EMA), and Member of the Committee for Evaluation of Medicines at the National Authority of Medicines and Health Products, I.P. (INFARMED).

The monitoring of substance use worldwide highlights a pandemic with profound social, health, and economic consequences, as the latest 2023 World Drug Report estimates that almost 300 million people worldwide have used substances of abuse during 2021, an increase of about 23% over 10 years. Despite their collective impact on the central nervous system, these substances significantly differ in their neurochemical processes, addictive tendencies, and overall health effects, and also toxicologically impact other organ systems (e.g., respiratory, cardiovascular, liver, and kidneys). Understanding the mechanisms underlying the toxicological effects of these substances of abuse is thus highly important for researchers, clinicians, and policy-makers to (1) ascertain their addictive potential and the mechanisms that lead to adverse health consequences, (2) uncover new and/or improved approaches for intoxication treatments and rehabilitation, and (3) take better informed regulatory decisions.

This Special Issue aims to collect original research articles and reviews on the molecular aspects of different drugs of abuse, investigating their pharmacological and toxicological impacts on the brain and other organs.

We look forward to receiving your contributions.

Dr. João Pedro Silva
Dr. Vera Marisa Costa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • toxicodynamic
  • toxicokinetic
  • amphetamine-type stimulants, cannabis and cannabinoids, cocaine, hallucinogens, new psychoactive substances, opioids
  • immune modulation

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Published Papers (3 papers)

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Research

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21 pages, 14567 KiB  
Article
Region-Specific Impact of Repeated Synthetic Cannabinoid Exposure and Withdrawal on Endocannabinoid Signaling, Gliosis, and Inflammatory Markers in the Prefrontal Cortex and Hippocampus
by Evelin Vadas, Antonio J. López-Gambero, Antonio Vargas, Miguel Rodríguez-Pozo, Patricia Rivera, Juan Decara, Antonia Serrano, Stella Martín-de-las-Heras, Fernando Rodríguez de Fonseca and Juan Suárez
Biomolecules 2025, 15(3), 417; https://doi.org/10.3390/biom15030417 - 14 Mar 2025
Viewed by 398
Abstract
Synthetic cannabinoid use raises concerns about its neuroinflammatory effects, including molecular adaptations of the endocannabinoid system (ECS) in the brain. This study investigates the pharmacological effects of 14-day repeated intraperitoneal administration, as well as 14-day administration followed by a 7-day withdrawal period of [...] Read more.
Synthetic cannabinoid use raises concerns about its neuroinflammatory effects, including molecular adaptations of the endocannabinoid system (ECS) in the brain. This study investigates the pharmacological effects of 14-day repeated intraperitoneal administration, as well as 14-day administration followed by a 7-day withdrawal period of two synthetic cannabinoids: WIN55,212-2 and HU-210. The study assessed gene expression and protein markers related to the ECS, gliosis, and inflammation in two brain regions critical for cognitive processes and memory—key components of addiction pathways—the prefrontal cortex (PFC) and the hippocampus of rats. Our findings showed that repeated WIN55,212-2 administration induced adaptations in the ECS and reduced IBA1, a glial protein marker, along with inflammatory responses likely mediated through CB2 activity. Notably, regional differences emerged in the hippocampus, where repeated administration of WIN55,212-2 and HU-210 increased IBA1 and inflammatory markers, effects unrelated to CB2 activity. Withdrawal from WIN55,212-2 in the PFC, as well as from both compounds in the hippocampus, decreased IBA1 levels. This was associated with altered protein expression of cannabinoid-synthesizing and degrading enzymes, favoring acylethanolamide synthesis. These findings highlight region-specific effects of synthetic cannabinoids on cannabinoid signaling, gliosis, and inflammation. Further research is needed to elucidate the long-term neurobiological consequences of synthetic cannabinoid use and withdrawal. Full article
(This article belongs to the Special Issue Molecular and Toxicological Profiling of Drugs of Abuse—in Honor of Professor Félix Carvalho)
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15 pages, 2522 KiB  
Article
Synthesis, Analytical Characterization, and Human CB1 Receptor Binding Studies of the Chloroindole Analogues of the Synthetic Cannabinoid MDMB-CHMICA
by Sascha Münster-Müller, Steven Hansen, Tobias Lucas, Arianna Giorgetti, Lukas Mogler, Svenja Fischmann, Folker Westphal, Volker Auwärter, Michael Pütz and Till Opatz
Biomolecules 2024, 14(11), 1414; https://doi.org/10.3390/biom14111414 - 6 Nov 2024
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Abstract
Synthetic cannabinoids (SCs) are one of the largest groups of new psychoactive substances (NPSs). However, the relationship between their chemical structure and the affinity to human CB1 receptors (hCB1), which mediates their psychotropic activity, is not well understood. Herein, the [...] Read more.
Synthetic cannabinoids (SCs) are one of the largest groups of new psychoactive substances (NPSs). However, the relationship between their chemical structure and the affinity to human CB1 receptors (hCB1), which mediates their psychotropic activity, is not well understood. Herein, the synthesis of the 2-, 4-, 5-, 6- and 7-chloroindole analogues of the synthetic cannabimimetic MDMB-CHMICA, along with their analytical characterization via ultraviolet–visible (UV/VIS), infrared (IR), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry, is described. Furthermore, all five derivatives of MDMB-CHMICA were analyzed for their hCB1 binding affinities. Chlorination at position 4 and 5 of the indole core reduced the binding affinity compared to MDMB-CHMICA, while the test compounds chlorinated in positions 2, 6, and 7 largely retained their binding affinities relative to the non-chlorinated parent compound. Full article
(This article belongs to the Special Issue Molecular and Toxicological Profiling of Drugs of Abuse—in Honor of Professor Félix Carvalho)
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Review

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22 pages, 1523 KiB  
Review
Genes, Cognition, and Their Interplay in Methamphetamine Use Disorder
by Ramisha Khan, Alyna Turner, Michael Berk, Ken Walder, Susan Rossell, Alexandre A. Guerin and Jee Hyun Kim
Biomolecules 2025, 15(2), 306; https://doi.org/10.3390/biom15020306 - 19 Feb 2025
Viewed by 529
Abstract
Methamphetamine use disorder is a pressing global health issue, often accompanied by significant cognitive deficits that impair daily functioning and quality of life and complicate treatment. Emerging evidence highlights the potential role of genetic factors in methamphetamine use disorder, particularly in association with [...] Read more.
Methamphetamine use disorder is a pressing global health issue, often accompanied by significant cognitive deficits that impair daily functioning and quality of life and complicate treatment. Emerging evidence highlights the potential role of genetic factors in methamphetamine use disorder, particularly in association with cognitive function. This review examines the key genetic and cognitive dimensions and their interplay in methamphetamine use disorder. There is converging evidence from several studies that genetic polymorphisms in BDNF, FAAH, SLC18A1, and SLC18A2 are associated with protection against or susceptibility to the disorder. In addition, people with methamphetamine use disorder consistently displayed impairments in cognitive flexibility and inhibitory control compared with people without the disorder. These cognitive domains were associated with reactivity to methamphetamine cues that were positively correlated with total years of methamphetamine use history. Emerging research also suggests that inhibitory control is negatively correlated with lower blood FAAH mRNA levels, while cognitive flexibility positively correlates with higher blood SLC18A2 mRNA levels, highlighting how genetic and cognitive dimensions interact in methamphetamine use disorder. We also include some future directions, emphasizing potential personalized therapeutic strategies that integrate genetic and cognitive insights. By drawing attention to the interplay between genes and cognition, we hope to advance our understanding of methamphetamine use disorder and inform the development of targeted interventions. Full article
(This article belongs to the Special Issue Molecular and Toxicological Profiling of Drugs of Abuse—in Honor of Professor Félix Carvalho)
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