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Biomedicines
Special Issues
Addiction: Molecular Research and Novel Therapeutic Approaches
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Addiction: Molecular Research and Novel Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 18457

Special Issue Editors

Dr. Francesco Di Carlo

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Guest Editor
Department of Neurosciences and Imaging, Chair of Psychiatry, University “G. D’Annunzio”, 66100 Chieti, Italy
Interests: substance use disorders; mood disorders; schizophrenia; neuromodulation; gut microbiota
Dr. Giovanni Martinotti

E-Mail Website
Guest Editor
1. Department of Neuroscience, Imaging, and Clinical Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy
2. Department of Pharmacy, Pharmacology and Clinical Science, University of Hertfordshire, Hatfield AL10 9EU, UK
Interests: phenomenology; neuroimaging; psychiatry; analytical philosophy; neuron; clinical psychology; psychopathology; philosophy of language; continental philosophy; ontology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Magí Farré

E-Mail Website
Guest Editor
1. Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
2. Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain
Interests: drug; substance use; alcohol; tobacco; cannabis

Special Issue Information

Dear Colleagues,

Addiction is a widespread, disabling condition, among the first causes of global burden of disease. Few pharmacological choices and non-pharmacological approaches (e.g., neuromodulation techniques) are currently available to deal with this condition. However, these approaches are not satisfactory. Additional treatments are needed, and in order to proceed further, a clearer understanding of biological processes that underlie addiction is needed.

Molecular mechanisms play a vital role in this understanding (https://www.mdpi.com/journal/ijms/special_issues/Insights_Psychiatry, https://www.mdpi.com/journal/ijms/special_issues/Endocannabinoids_2). We need to integrate altered molecular pathways with disease expression, behavior, and neuronal circuitry, and to form a complete theory with significant clinical implications, both for diagnosis and treatment.

This Special Issue is dedicated to molecular research in the field of addiction. Both substance use disorders and novel behavioral addictions are to be considered the subject of the Issue. Manuscripts about biomarkers, genetics, pathophysiological mechanisms that underlie the disorder, and translational research are particularly welcome. On the side of treatments, manuscripts regarding pharmacological approaches are of particular interest for this Special Issue. Manuscripts dealing with non-pharmacological approaches with a strong biological rationale (e.g., neuromodulation techniques) are also welcome.

Dr. Francesco Di Carlo
Dr. Giovanni Martinotti
Prof. Dr. Magí Farré
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. Biomedicines 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 2600 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

  • addiction
  • substance use disorders
  • biomarkers
  • psychopharmacology
  • neuromodulation
  • diagnosis
  • treatment

Published Papers (5 papers)

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Research

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15 pages, 1809 KiB  
Article
Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences
by Augusta Pisanu, Giacomo Lo Russo, Giuseppe Talani, Jessica Bratzu, Carlotta Siddi, Fabrizio Sanna, Marco Diana, Patrizia Porcu, Maria Antonietta De Luca and Liana Fattore
Biomedicines 2022, 10(10), 2336; https://doi.org/10.3390/biomedicines10102336 - 20 Sep 2022
Cited by 4 | Viewed by 2383
Abstract
The illicit drug market of novel psychoactive substances (NPSs) is expanding, becoming an alarming threat due to increasing intoxication cases and insufficient (if any) knowledge of their effects. Phenethylamine 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) and synthetic cathinone 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) are new, emerging NPSs suggested to be [...] Read more.
The illicit drug market of novel psychoactive substances (NPSs) is expanding, becoming an alarming threat due to increasing intoxication cases and insufficient (if any) knowledge of their effects. Phenethylamine 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) and synthetic cathinone 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) are new, emerging NPSs suggested to be particularly dangerous. This study verified whether these two new drugs (i) possess abuse liability, (ii) alter plasma corticosterone levels, and (iii) interfere with dopaminergic transmission; male and female adolescent rats were included to evaluate potential sex differences in the drug-induced effects. Findings show that the two NPSs are not able to sustain reliable self-administration behavior in rats, with cumulatively earned injections of drugs being not significantly different from cumulatively earned injections of saline in control groups. Yet, at the end of the self-administration training, females (but not males) exhibited higher plasma corticosterone levels after chronic exposure to low levels of 3,4-MDPHP (but not of 2-Cl-4,5-MDMA). Finally, electrophysiological patch-clamp recordings in the rostral ventral tegmental area (rVTA) showed that both drugs are able to increase the firing rate of rVTA dopaminergic neurons in males but not in females, confirming the sex dimorphic effects of these two NPSs. Altogether, this study demonstrates that 3,4-MDPHP and 2-Cl-4,5-MDMA are unlikely to induce dependence in occasional users but can induce other effects at both central and peripheral levels that may significantly differ between males and females. Full article
(This article belongs to the Special Issue Addiction: Molecular Research and Novel Therapeutic Approaches)
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9 pages, 1268 KiB  
Article
UFR2709, an Antagonist of Nicotinic Acetylcholine Receptors, Delays the Acquisition and Reduces Long-Term Ethanol Intake in Alcohol-Preferring UChB Bibulous Rats
by Gabriel Gálvez, Juan Pablo González-Gutiérrez, Martín Hödar-Salazar, Ramón Sotomayor-Zárate, María Elena Quintanilla, María Elena Quilaqueo, Mario Rivera-Meza and Patricio Iturriaga-Vásquez
Biomedicines 2022, 10(7), 1482; https://doi.org/10.3390/biomedicines10071482 - 22 Jun 2022
Cited by 3 | Viewed by 1780
Abstract
Alcoholism is a worldwide public health problem with high economic cost and which affects health and social behavior. It is estimated that alcoholism kills 3 million people globally, while in Chile it is responsible for around 9 thousand deaths per year. Nicotinic acetylcholine [...] Read more.
Alcoholism is a worldwide public health problem with high economic cost and which affects health and social behavior. It is estimated that alcoholism kills 3 million people globally, while in Chile it is responsible for around 9 thousand deaths per year. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels expressed in the central nervous system, and they were suggested to modulate the ethanol mechanism involved in abuse and dependence. Previous work demonstrated a short-term treatment with UFR2709, a nAChRs antagonist, which reduced ethanol intake using a two-bottle free-choice paradigm in University of Chile bibulous (UChB) rats. Here, we present evidence of the UFR2709 efficacy in reducing the acquisition and long-term ethanol consumption. Our results show that UFR2709 (2.5 mg/kg i.p.) reduces the seek behavior and ethanol intake, even when the drug administration was stopped, and induced a reduction in the overall ethanol intake by around 55%. Using naïve UChB bibulous rats, we demonstrate that UFR2709 could delay and reduce the genetically adaptive impulse to seek and drink ethanol and prevent its excessive intake. Full article
(This article belongs to the Special Issue Addiction: Molecular Research and Novel Therapeutic Approaches)
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16 pages, 4804 KiB  
Article
Effect of Prenatal Opioid Exposure on the Human Placental Methylome
by Kristyn N. Borrelli, Elisha M. Wachman, Jacob A. Beierle, Elizabeth S. Taglauer, Mayuri Jain, Camron D. Bryant and Huiping Zhang
Biomedicines 2022, 10(5), 1150; https://doi.org/10.3390/biomedicines10051150 - 17 May 2022
Cited by 9 | Viewed by 3332
Abstract
Prenatal exposure to addictive drugs can lead to placental epigenetic modifications, but a methylome-wide evaluation of placental DNA methylation changes after prenatal opioid exposure has not yet been performed. Placental tissue samples were collected at delivery from 19 opioid-exposed and 20 unexposed control [...] Read more.
Prenatal exposure to addictive drugs can lead to placental epigenetic modifications, but a methylome-wide evaluation of placental DNA methylation changes after prenatal opioid exposure has not yet been performed. Placental tissue samples were collected at delivery from 19 opioid-exposed and 20 unexposed control full-term pregnancies. Placental DNA methylomes were profiled using the Illumina Infinium HumanMethylationEPIC BeadChip. Differentially methylated CpG sites associated with opioid exposure were identified with a linear model using the ‘limma’ R package. To identify differentially methylated regions (DMRs) spanning multiple CpG sites, the ‘DMRcate’ R package was used. The functions of genes mapped by differentially methylated CpG sites and DMRs were further annotated using Enrichr. Differentially methylated CpGs (n = 684, unadjusted p < 0.005 and |∆β| ≥ 0.05) were mapped to 258 genes (including PLD1, MGAM, and ALCS2). Differentially methylated regions (n = 199) were located in 174 genes (including KCNMA1). Enrichment analysis of the top differentially methylated CpG sites and regions indicated disrupted epigenetic regulation of genes involved in synaptic structure, chemical synaptic transmission, and nervous system development. Our findings imply that placental epigenetic changes due to prenatal opioid exposure could result in placental dysfunction, leading to abnormal fetal brain development and the symptoms of opioid withdrawal in neonates. Full article
(This article belongs to the Special Issue Addiction: Molecular Research and Novel Therapeutic Approaches)
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Review

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22 pages, 863 KiB  
Review
Epigenetic Studies for Evaluation of NPS Toxicity: Focus on Synthetic Cannabinoids and Cathinones
by Leila Mazdai, Matteo Fabbri, Micaela Tirri, Giorgia Corli, Raffaella Arfè, Beatrice Marchetti, Sabrine Bilel, Eva Bergamin, Rosa Maria Gaudio, Michele Rubini, Fabio De-Giorgio and Matteo Marti
Biomedicines 2022, 10(6), 1398; https://doi.org/10.3390/biomedicines10061398 - 13 Jun 2022
Cited by 2 | Viewed by 3667
Abstract
In the recent decade, numerous new psychoactive substances (NPSs) have been added to the illicit drug market. These are synthetized to mimic the effects of classic drugs of abuse (i.e., cannabis, cocaine, etc.), with the purpose of bypassing substance legislations and increasing the [...] Read more.
In the recent decade, numerous new psychoactive substances (NPSs) have been added to the illicit drug market. These are synthetized to mimic the effects of classic drugs of abuse (i.e., cannabis, cocaine, etc.), with the purpose of bypassing substance legislations and increasing the pharmacotoxicological effects. To date, research into the acute pharmacological effects of new NPSs is ongoing and necessary in order to provide an appropriate contribution to public health. In fact, multiple examples of NPS-related acute intoxication and mortality have been recorded in the literature. Accordingly, several in vitro and in vivo studies have investigated the pharmacotoxicological profiles of these compounds, revealing that they can cause adverse effects involving various organ systems (i.e., cardiovascular, respiratory effects) and highlighting their potential increased consumption risks. In this sense, NPSs should be regarded as a complex issue that requires continuous monitoring. Moreover, knowledge of long-term NPS effects is lacking. Because genetic and environmental variables may impact NPS responses, epigenetics may aid in understanding the processes behind the harmful events induced by long-term NPS usage. Taken together, “pharmacoepigenomics” may provide a new field of combined study on genetic differences and epigenetic changes in drug reactions that might be predictive in forensic implications. Full article
(This article belongs to the Special Issue Addiction: Molecular Research and Novel Therapeutic Approaches)
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Other

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27 pages, 959 KiB  
Systematic Review
Misuse of Anticholinergic Medications: A Systematic Review
by Stefania Chiappini, Alessio Mosca, Andrea Miuli, Francesco Maria Semeraro, Gianluca Mancusi, Maria Chiara Santovito, Francesco Di Carlo, Mauro Pettorruso, Amira Guirguis, John Martin Corkery, Giovanni Martinotti, Fabrizio Schifano and Massimo Di Giannantonio
Biomedicines 2022, 10(2), 355; https://doi.org/10.3390/biomedicines10020355 - 01 Feb 2022
Cited by 10 | Viewed by 6082
Abstract
(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is [...] Read more.
(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP (n = 25), and benztropine (n = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues. Full article
(This article belongs to the Special Issue Addiction: Molecular Research and Novel Therapeutic Approaches)
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