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Biomedicines
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Advances in Treatment of Drug Addiction
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Advances in Treatment of Drug Addiction

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 6404

Special Issue Editors

Dr. Javier Navarro-Zaragoza

E-Mail Website
Guest Editor
Department of Pharmacology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
Interests: neurobiological mechanisms; drug addiction; neuropharmacology
Special Issues, Collections and Topics in MDPI journals
Dr. Pilar Almela

E-Mail Website
Guest Editor
Department of Pharmacology, School of Medicine, Biomedical Research Institute of Murcia (IMIB), University of Murcia, 30100 Murcia, Spain
Interests: neurobiological mechanisms; drug addiction; neuropharmacology

Special Issue Information

Dear Colleagues,

Drug addiction is a substantial problem in several countries. In the US, for example, more than 100,000 people died from drug overdose in the last twelve months. Opioid addiction is currently the causative drug in 75% of these overdoses. Other drugs such as cocaine or newly designed drugs are increasing too and sometimes dishabituation is ineffective. Relapses in drug addiction are one of the primary problems in this disease due to the neurobehavioral changes that occur. Relapses can happen even after years of withdrawal. On the other hand, in recent years different research institutes have been developing trials with new treatments to help avoid relapses. Some of them are in phase II or III and are targeted to different neurocircuitry or systems (i.e., the extended amygdala) involved in stress, which is believed to be a key factor. Some new dosage forms are also being tested in dishabituation.

In this Special Issue we intend to compile new advances related to drug addiction, focusing on treatment and how to improve drug abusers' quality of life.

Dr. Javier Navarro-Zaragoza
Dr. Pilar Almela
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

  • drug addiction
  • treatment
  • withdrawal
  • relapse
  • pharmacokinetics
  • stress
  • dopamine
  • noradrenergic system
  • drug abuse

Published Papers (4 papers)

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Research

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13 pages, 3133 KiB  
Article
Methadone Maintenance and QT-Interval: Prevalence and Risk Factors—Is It Effective to Switch Therapy to Levomethadone?
by Laura Santin, Giuseppe Verlato, Ahmad Tfaily, Roberto Manera, Giuseppe Zinfollino, Francesca Fusina and Fabio Lugoboni
Biomedicines 2023, 11(8), 2109; https://doi.org/10.3390/biomedicines11082109 - 26 Jul 2023
Viewed by 934
Abstract
Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose [...] Read more.
Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this retrospective study was to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett’s formula. Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. In total, 14% of the sample (23 patients) showed a prolongation of the QTc interval (>470 ms in males and >480 ms in females); 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone—in 90% of these patients, a normalization in the QTc length was established. This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of careful electrocardiographic monitoring in methadone-treated patients. Full article
(This article belongs to the Special Issue Advances in Treatment of Drug Addiction)
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16 pages, 4209 KiB  
Article
Cocaine Regulates NLRP3 Inflammasome Activity and CRF Signaling in a Region- and Sex-Dependent Manner in Rat Brain
by Yan Cheng, Rachael Elizabeth Dempsey, Soheil Kazemi Roodsari, Dorela D. Shuboni-Mulligan, Olivier George, Larry D. Sanford and Ming-Lei Guo
Biomedicines 2023, 11(7), 1800; https://doi.org/10.3390/biomedicines11071800 - 23 Jun 2023
Viewed by 1165
Abstract
Cocaine, one of the most abused drugs worldwide, is capable of activating microglia in vitro and in vivo. Several neuroimmune pathways have been suggested to play roles in cocaine-mediated microglial activation. Previous work showed that cocaine activates microglia in a region-specific manner in [...] Read more.
Cocaine, one of the most abused drugs worldwide, is capable of activating microglia in vitro and in vivo. Several neuroimmune pathways have been suggested to play roles in cocaine-mediated microglial activation. Previous work showed that cocaine activates microglia in a region-specific manner in the brains of self-administered mice. To further characterize the effects of cocaine on microglia and neuroimmune signaling in vivo, we utilized the brains from both sexes of outbred rats with cocaine self-administration to explore the activation status of microglia, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activity, corticotropin-releasing factor (CRF) signaling, and NF-κB levels in the striatum and hippocampus (HP). Age-matched rats of the same sex (drug naïve) served as controls. Our results showed that cocaine increased neuroinflammation in the striatum and HP of both sexes with a relatively higher increases in male brains. In the striatum, cocaine upregulated NLRP3 inflammasome activity and CRF levels in males but not in females. In contrast, cocaine increased NLRP3 inflammasome activity in the HP of females but not in males, and no effects on CRF signaling were observed in this region of either sex. Interestingly, cocaine increased NF-κB levels in the striatum and HP with no sex difference. Taken together, our results provide evidence that cocaine can exert region- and sex-specific differences in neuroimmune signaling in the brain. Targeting neuroimmune signaling has been suggested as possible treatment for cocaine use disorders (CUDs). Our current results indicate that sex should be taken into consideration when determining the efficacy of these new therapeutic approaches. Full article
(This article belongs to the Special Issue Advances in Treatment of Drug Addiction)
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22 pages, 6794 KiB  
Article
The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes, Cortex, and Hippocampus; Comparison with Changes Induced by Morphine
by Hana Ujcikova, Lenka Roubalova, Yeon Sun Lee, Jirina Slaninova, Jana Brejchova and Petr Svoboda
Biomedicines 2022, 10(8), 1969; https://doi.org/10.3390/biomedicines10081969 - 14 Aug 2022
Cited by 3 | Viewed by 1885
Abstract
This work aimed to test the effect of 7-day exposure of rats to multifunctional enkephalin analogs LYS739 and LYS744 at doses of 3 mg/kg and 10 mg/kg on the protein composition of rat spleen lymphocytes, brain cortex, and hippocampus. Alterations of proteome induced [...] Read more.
This work aimed to test the effect of 7-day exposure of rats to multifunctional enkephalin analogs LYS739 and LYS744 at doses of 3 mg/kg and 10 mg/kg on the protein composition of rat spleen lymphocytes, brain cortex, and hippocampus. Alterations of proteome induced by LYS739 and LYS744 were compared with those elicited by morphine. The changes in rat proteome profiles were analyzed by label-free quantification (MaxLFQ). Proteomic analysis indicated that the treatment with 3 mg/kg of LYS744 caused significant alterations in protein expression levels in spleen lymphocytes (45), rat brain cortex (31), and hippocampus (42). The identified proteins were primarily involved in RNA processing and the regulation of cytoskeletal dynamics. In spleen lymphocytes, the administration of the higher 10 mg/kg dose of both enkephalin analogs caused major, extensive modifications in protein expression levels: LYS739 (119) and LYS744 (182). Among these changes, the number of proteins associated with immune responses and apoptotic processes was increased. LYS739 treatment resulted in the highest number of alterations in the rat brain cortex (152) and hippocampus (45). The altered proteins were functionally related to the regulation of transcription and cytoskeletal reorganization, which plays an essential role in neuronal plasticity. Administration with LYS744 did not increase the number of altered proteins in the brain cortex (26) and hippocampus (26). Our findings demonstrate that the effect of κ-OR full antagonism of LYS744 is opposite in the central nervous system and the peripheral region (spleen lymphocytes). Full article
(This article belongs to the Special Issue Advances in Treatment of Drug Addiction)
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Review

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11 pages, 1316 KiB  
Review
GIRK Channels as Candidate Targets for the Treatment of Substance Use Disorders
by Hiroko Kotajima-Murakami, Soichiro Ide and Kazutaka Ikeda
Biomedicines 2022, 10(10), 2552; https://doi.org/10.3390/biomedicines10102552 - 13 Oct 2022
Cited by 1 | Viewed by 1838
Abstract
Substance use disorders (SUDs) are chronic, lifelong disorders that have serious consequences. Repeated substance use alters brain function. G-protein-activated inwardly rectifying potassium (GIRK) channels are expressed widely in the brain, including the reward system, and regulate neuronal excitability. Functional GIRK channels are identified [...] Read more.
Substance use disorders (SUDs) are chronic, lifelong disorders that have serious consequences. Repeated substance use alters brain function. G-protein-activated inwardly rectifying potassium (GIRK) channels are expressed widely in the brain, including the reward system, and regulate neuronal excitability. Functional GIRK channels are identified as heterotetramers of GIRK subunits (GIRK1–4). The GIRK1, GIRK2, and GIRK3 subunits are mainly expressed in rodent brain regions, and various addictive substances act on the brain through GIRK channels. Studies with animals (knockout and missense mutation animals) and humans have demonstrated the involvement of GIRK channels in the effects of addictive substances. Additionally, GIRK channel blockers affect behavioral responses to addictive substances. Thus, GIRK channels play a key role in SUDs, and GIRK channel modulators may be candidate medications. Ifenprodil is a GIRK channel blocker that does not have serious side effects. Two clinical trials were conducted to investigate the effects of ifenprodil in patients with alcohol or methamphetamine use disorder. Although the number of participants was relatively low, evidence of its safety and efficacy was found. The present review discusses the potential of GIRK channel modulators as possible medications for addiction. Therapeutic agents that target GIRK channels may be promising for the treatment of SUDs. Full article
(This article belongs to the Special Issue Advances in Treatment of Drug Addiction)
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