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Pharmaceuticals
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Pharmacology and Toxicology of Opioids
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Pharmacology and Toxicology of Opioids

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

Deadline for manuscript submissions: 25 April 2025 | Viewed by 6134

Special Issue Editors

Dr. Juliana Faria

E-Mail Website
Guest Editor
1. 1H-TOXRUN—One Health Toxicology Research Unit, University Institute of Health Sciences—CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal
2. UCIBIO-REQUIMTE—Applied Molecular Biosciences Unit-Network of Chemistry and Technology, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Interests: opioid pharmacology; prescription opioids; toxicity assays; toxicity mechanisms; in vivo models; in vitro models
Dr. Joana Barbosa

E-Mail Website
Guest Editor
1. 1H-TOXRUN—One Health Toxicology Research Unit, University Institute of Health Sciences—CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal 2. UCIBIO-REQUIMTE—Applied Molecular Biosciences Unit-Network of Chemistry and Technology, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Interests: toxicology; opioid pharmacology; opioid pharmacokinetics; opioid pharmacodynamics; toxicity biomarkers; adverse outcome pathways; toxicity screening; in vitro assays; in vivo assays
Prof. Dr. Ricardo Dinis-Oliveira

E-Mail Website
Guest Editor
1. 1H-TOXRUN—One Health Toxicology Research Unit, University Institute of Health Sciences—CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal
2. UCIBIO-REQUIMTE—Applied Molecular Biosciences Unit of Network of Chemistry and Technology, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
3. Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal
4. FOREN—Forensic Science Experts, 4200-604 Porto, Portugal
Interests: toxicology; psychoactive substances; forensic sciences; drugs; opioids; biomedical research; scientometrics; scientific medical writing; pedagogical innovation; real-world evidence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Opioids are a broad group of drugs that include illegal drugs and medicines. In the pharmacological context, opioids are currently used as a gold standard for the treatment of moderate to severe pain. Pain is a complex and subjective experience, and is a symptom associated with several pathologies, many of which are extremely frequent, leading to the widespread consumption of opioids. Despite their high analgesic efficiency, the incidence of side effects and adverse reactions, poisoning cases, including fatal intoxications, as well as cases of addiction, are growing along with the increase in their use and misuse. In fact, opioid consumption is leading to an opioid epidemic and a public health crisis. 

In this context, it is important to broaden the knowledge of opioid pharmacology and toxicity mechanisms to improve their therapeutic efficacy and lower the rate of adverse effects, ultimately improving the quality of life of many patients. Furthermore, it is also important to understand and decrease the potential for opioid dependence, besides searching for new analgesic opioids. Therefore, in this Special Issue, authors are invited to submit original papers, review, communications, perspectives and opinion articles on all relevant aspects of opioid pharmacology and toxicology. 

Research areas may include the following:

  • In vitro and in vivo studies on opioid toxicity;
  • In vitro and in vivo studies on opioid structure–activity;
  • Pharmacokinetic and pharmacodynamic studies;
  • Behavioral studies;
  • New advancements in opioid pharmacology, including (but not limited to) new opioid drug candidates;
  • New opioid quantification methodologies

Dr. Juliana Faria
Dr. Joana Barbosa
Prof. Dr. Ricardo Dinis-Oliveira
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. Pharmaceuticals 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 2900 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

  • opioid toxicity
  • opioid pharmacodynamics
  • opioid pharmacokinetics
  • opioid pharmacogenetics
  • prescription opioids
  • toxicity assays
  • in vivo
  • in vitro
  • abuse
  • dependence

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Published Papers (3 papers)

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Research

15 pages, 7500 KiB  
Article
The Comparative Effect of Morphine on Proliferation of Cancer Cell Lines Originating from Different Organs: An In Vitro Study
by Lydia Whitham, Mahdi Sheikh, Markus W. Hollmann and Marie-Odile Parat
Pharmaceuticals 2024, 17(12), 1656; https://doi.org/10.3390/ph17121656 - 9 Dec 2024
Viewed by 728
Abstract
Background/Objectives: Opium consumption was recently classified by the International Agency for Research on Cancer (IARC) monograph as carcinogenic to humans based on strong evidence for cancers of the larynx, lung, and urinary bladder, and limited evidence for cancers of the oesophagus, stomach, [...] Read more.
Background/Objectives: Opium consumption was recently classified by the International Agency for Research on Cancer (IARC) monograph as carcinogenic to humans based on strong evidence for cancers of the larynx, lung, and urinary bladder, and limited evidence for cancers of the oesophagus, stomach, pancreas, and pharynx. This poses the question of a potential pro-cancer effect of pharmaceutical opioid analgesics. In vitro studies employing a variety of experimental conditions suggest that opioid alkaloids have proliferative or antiproliferative effects. We set out to reconcile this discrepancy and explore the hypothesis that opioids promote cancer cell proliferation in an organ-dependent fashion. Methods: Using strictly controlled conditions, we tested the effect of morphine on the proliferation of a series of human cancer cell lines isolated from organs where cancer risk was linked causally to opium consumption in human studies (i.e., lung, bladder, and larynx), or control organs where no link between cancer risk and opium consumption has been reported in human studies (i.e., breast, colon, prostate). Results: Our results showed a minimal effect on proliferation on any cell line and no trend supporting an organ-specific effect of morphine. Conclusions: This argues against a direct effect of opioids on tumour cell proliferation to support their organ-specific effect. Full article
(This article belongs to the Special Issue Pharmacology and Toxicology of Opioids)
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15 pages, 1206 KiB  
Article
Fentanyl Overdose Causes Prolonged Cardiopulmonary Dysregulation in Male SKH1 Mice
by Mackenzie Newman, Heather Connery, Swapna Kannan, Aarti Gautam, Rasha Hammamieh, Nabarun Chakraborty and Jonathan Boyd
Pharmaceuticals 2024, 17(7), 941; https://doi.org/10.3390/ph17070941 - 14 Jul 2024
Viewed by 1667
Abstract
Fentanyl overdose is a survivable condition that commonly resolves without chronic overt changes in phenotype. While the acute physiological effects of fentanyl overdose, such as opioid-induced respiratory depression (OIRD) and Wooden Chest Syndrome, represent immediate risks of lethality, little is known about longer-term [...] Read more.
Fentanyl overdose is a survivable condition that commonly resolves without chronic overt changes in phenotype. While the acute physiological effects of fentanyl overdose, such as opioid-induced respiratory depression (OIRD) and Wooden Chest Syndrome, represent immediate risks of lethality, little is known about longer-term systemic or organ-level impacts for survivors. In this study, we investigated the effects of a single, bolus fentanyl overdose on components of the cardiopulmonary system up to one week post. SKH1 mice were administered subcutaneous fentanyl at the highest non-lethal dose (62 mg/kg), LD10 (110 mg/kg), or LD50 (135 mg/kg), before euthanasia at 40 min, 6 h, 24 h, or 7 d post-exposure. The cerebral cortex, heart, lungs, and plasma were assayed using an immune monitoring 48-plex panel. The results showed significantly dysregulated cytokine, chemokine, and growth factor concentrations compared to time-matched controls, principally in hearts, then lungs and plasma to a lesser extent, for the length of the study, with the cortex largely unaffected. Major significant analytes contributing to variance included eotaxin-1, IL-33, and betacellulin, which were generally downregulated across time. The results of this study suggest that cardiopulmonary toxicity may persist from a single fentanyl overdose and have wide implications for the endurance of the expanding population of survivors. Full article
(This article belongs to the Special Issue Pharmacology and Toxicology of Opioids)
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21 pages, 2142 KiB  
Article
Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity
by Cristiana Soares-Cardoso, Sandra Leal, Susana I. Sá, Rita Dantas-Barros, Ricardo Jorge Dinis-Oliveira, Juliana Faria and Joana Barbosa
Pharmaceuticals 2024, 17(6), 796; https://doi.org/10.3390/ph17060796 - 17 Jun 2024
Cited by 1 | Viewed by 2015
Abstract
Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. [...] Read more.
Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. The hippocampal formation is known to participate in memory and learning processes and has been documented to contribute to opioid dependence. Accordingly, the present study assessed molecular and cellular alterations in the hippocampal formation of Wistar rats intraperitoneally administered with 50 mg/kg tramadol or tapentadol for eight alternate days. Alterations were found in serum hydrogen peroxide, cysteine, homocysteine, and dopamine concentrations upon exposure to one or both opioids, as well as in hippocampal 8-hydroxydeoxyguanosine and gene expression levels of a panel of neurotoxicity, neuroinflammation, and neuromodulation biomarkers, assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of hippocampal formation sections showed increased glial fibrillary acidic protein (GFAP) and decreased cluster of differentiation 11b (CD11b) protein expression, suggesting opioid-induced astrogliosis and microgliosis. Collectively, the results emphasize the hippocampal neuromodulator effects of tramadol and tapentadol, with potential behavioral implications, underlining the need to prescribe and use both opioids cautiously. Full article
(This article belongs to the Special Issue Pharmacology and Toxicology of Opioids)
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