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Toxics
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Toxicity of Central Nervous System (CNS) Modulators
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Toxicity of Central Nervous System (CNS) Modulators

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 6227

Special Issue Editors

Prof. Dr. Youssef Sari

E-Mail Website
Guest Editor
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH 43614, USA
Interests: the neuropharmacology and toxicology of drugs of abuse in the central nervous and peripheral systems; drug discovery
Special Issues, Collections and Topics in MDPI journals
Dr. Fawaz Alasmari

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Interests: the toxicological and pharmacological effects of drugs of abuse in the brain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The main focus of this Special Issue is to identify the toxicological effects of drugs that are considered modulators and can be used to treat diseases and disorders associated with the central nervous system. The Special Issue also focuses on the toxicological effects of drugs of abuse that affect the CNS. These drugs of abuse include ethanol, cannabis, psychostimulants (e.g., methamphetamine, cathinone, cocaine and others), opioids, and nicotine, as well as other synthetic drugs (heroin, balt salt, etc.) and other illicit drugs. This Special Issue seeks research articles that mainly investigate the toxicological effects of CNS modulators in acute and chronic paradigms. CNS modulators include approved medications and illicit drugs.

We invite investigators from different research areas to present their studies on the toxicological effects of CNS modulators which can be illicit and non-illicit drugs that have modulatory effects in the brain. We also encourage investigators to submit review articles or method research articles centered around the toxicity of CNS modulators.

Prof. Dr. Youssef Sari
Dr. Fawaz Alasmari
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. Toxics 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

  • toxicity
  • opioids
  • substances of abuse
  • illicit drugs
  • methamphetamine
  • cannabis
  • drugs of abuse
  • psychostimulants
  • nicotine

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

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Research

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12 pages, 1353 KiB  
Article
Chlorella vulgaris Supplementation Attenuates Lead Accumulation, Oxidative Stress, and Memory Impairment in Rats
by Juan Pablo Diaz, Eduardo Pena, Samia El Alam, Cecilia Matte, Isaac Cortés, Leonardo Figueroa, Patricia Siques and Julio Brito
Toxics 2025, 13(4), 313; https://doi.org/10.3390/toxics13040313 - 18 Apr 2025
Viewed by 166
Abstract
Lead is a harmful heavy metal known to alter the environment and affect human health. Several industries have contributed to the increase in lead contamination, making it a major global concern. Thus, remediation strategies are necessary to prevent lead bioaccumulation and deleterious health [...] Read more.
Lead is a harmful heavy metal known to alter the environment and affect human health. Several industries have contributed to the increase in lead contamination, making it a major global concern. Thus, remediation strategies are necessary to prevent lead bioaccumulation and deleterious health effects. The aim of this study was to determine the capacity of the green microalga Chlorella vulgaris (C. vulgaris or CV) to remove lead in an animal model and prevent the accumulation of this heavy metal in the principal organs (brain, liver, and kidney) and blood. Forty male Wistar rats were randomly assigned to four groups (n = 10): control group (CT); C. vulgaris supplementation group, 5% of the diet (CV); lead acetate administration group, 500 ppm (Pb); and C. vulgaris supplementation group, 5% of the diet plus lead acetate administration group, 500 ppm (CV–Pb). After 4 weeks of exposure, we measured lead accumulation, memory function, oxidative stress, and antioxidant activity (SOD and GSH). Lead exposure altered memory function, increased oxidative stress in the brain and kidney, and increased SOD activity in the brain. Supplementation with C. vulgaris restored memory function to control levels; reduced oxidative stress in the brain and kidney; and decreased the accumulation of lead in the liver, kidney, and blood of rats exposed to lead. Based on our results, C. vulgaris is a lead chelating and antioxidant agent in animal models. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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18 pages, 556 KiB  
Article
A Quantitative and Comparative Study of Heroin-Related Metabolites in Different Postmortem Fluids and Tissues
by Torki A. Zughaibi, Ziad Assiri, Ahmed Mirza, Hassan Alharbi, Abdulnasser E. Alzahrani, Sultan A. Alahmadi, Faiz Alsolami, Adel Al-Saadi, Mohamed Almoustady, Sultan Al-Zahrani, Majda Altowairqi and Ahmed I. Al-Asmari
Toxics 2025, 13(3), 229; https://doi.org/10.3390/toxics13030229 - 20 Mar 2025
Viewed by 249
Abstract
This study assessed and compared the postmortem concentrations of 6-monoacetylmorphine [6-MAM] and 6-acetylcodeine [6-AC], morphine, and codeine in various tissues and fluids from 52 postmortem cases related to heroin use. Samples were received at the Poison Control and Forensic Chemistry Center in Jeddah, [...] Read more.
This study assessed and compared the postmortem concentrations of 6-monoacetylmorphine [6-MAM] and 6-acetylcodeine [6-AC], morphine, and codeine in various tissues and fluids from 52 postmortem cases related to heroin use. Samples were received at the Poison Control and Forensic Chemistry Center in Jeddah, Saudi Arabia, and analyzed using liquid chromatography–mass spectrometry. Descriptive and inferential statistics, including median, range, variability, and outliers, were used for analysis. The results showed significant variability in heroin and metabolite concentrations across different fluids and tissues. Tissue specimens were analyzed in 38 cases (73%), with 50% of cases exhibiting putrefaction. Blood and tissue samples were available in 39 cases, highlighting the need for alternative specimens in challenging cases. Notably, heroin metabolites were detected in unique matrices, such as nasal swabs, bladder tissues, lung tissues, and small intestine tissues, underscoring the potential of these samples in forensic investigations, especially when traditional bodily fluids are unavailable or compromised. These findings suggest that environmental factors, timing of substance use, and postmortem changes influence substance distribution, emphasizing the need to consider the location of death when interpreting toxicological results for accurate forensic analysis. This study provides valuable insights into the distribution, correlation, and significance of heroin and its metabolites in postmortem samples, aiding the confirmation of heroin overdose. These findings contribute to the limited data on postmortem cases in the Middle East and North Africa, particularly Saudi Arabia, supporting efforts to curb drug abuse in this region. This knowledge can inform public health strategies and forensic practices, ultimately aiding efforts to address and mitigate drug abuse. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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20 pages, 4171 KiB  
Article
Neuroinflammation and Neurometabolomic Profiling in Fentanyl Overdose Mouse Model Treated with Novel β-Lactam, MC-100093, and Ceftriaxone
by Mohammed S. Alasmari, Fawaz Alasmari, Shakir D. Alsharari, Abdullah F. Alasmari, Nemat Ali, Syed Rizwan Ahamad, Abdullah M. Alghamdi, Aban A. Kadi, Alaa M. Hammad, Yousif S. Mohamed Ali, Wayne E. Childers, Magid Abou-Gharbia and Youssef Sari
Toxics 2024, 12(8), 604; https://doi.org/10.3390/toxics12080604 - 19 Aug 2024
Cited by 1 | Viewed by 1547
Abstract
Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and [...] Read more.
Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and β-lactams effectively enhance its expression and function. In the current study, we characterized the metabolomic profile of the nucleus accumbens (NAc) in fentanyl-overdose mouse models, and we evaluated the protective effects of the functional enhancement of GLT-1 using β-lactams, ceftriaxone, and MC-100093. BALB/c mice were divided into four groups: control, fentanyl, fentanyl/ceftriaxone, and fentanyl/MC-100093. While the control group was intraperitoneally (i.p.) injected with normal saline simultaneously with other groups, all fentanyl groups were i.p. injected with 1 mg/kg of fentanyl as an overdose after habituation with four repetitive non-consecutive moderate doses (0.05 mg/kg) of fentanyl for a period of seven days. MC-100093 (50 mg/kg) and ceftriaxone (200 mg/kg) were i.p. injected from days 5 to 9. Gas chromatography–mass spectrometry (GC-MS) was used for metabolomics, and Western blotting was performed to determine the expression of target proteins. Y-maze spontaneous alternation performance and the open field activity monitoring system were used to measure behavioral manifestations. Fentanyl overdose altered the abundance of about 30 metabolites, reduced the expression of GLT-1, and induced the expression of inflammatory mediators IL-6 and TLR-4 in the NAc. MC-100093 and ceftriaxone attenuated the effects of fentanyl-induced downregulation of GLT-1 and upregulation of IL-6; however, only ceftriaxone attenuated fentanyl-induced upregulation of TRL4 expression. Both of the β-lactams attenuated the effects of fentanyl overdose on locomotor activities but did not induce significant changes in the overall metabolomic profile. Our findings revealed that the exposure to a high dose of fentanyl causes alterations in key metabolic pathways in the NAc. Pretreatment with ceftriaxone and MC-100093 normalized fentanyl-induced downregulation of GLT-1 expression with subsequent attenuation of neuroinflammation as well as the hyperactivity, indicating that β-lactams may be promising drugs for treating fentanyl use disorder. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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17 pages, 3057 KiB  
Article
Green Tea Polyphenol Nanoparticles Reduce Anxiety Caused by Tobacco Smoking Withdrawal in Rats by Suppressing Neuroinflammation
by Alaa M. Hammad, Lujain F. Alzaghari, Malek Alfaraj, Vanessa Lux and Suhair Sunoqrot
Toxics 2024, 12(8), 598; https://doi.org/10.3390/toxics12080598 - 18 Aug 2024
Cited by 2 | Viewed by 1352
Abstract
Repeated exposure to tobacco smoke causes neuroinflammation and neuroplasticity, which correlates with smoking withdrawal-induced anxiety. The purpose of this study was to investigate the anticipated involvement of antioxidant-rich nanoparticles (NPs) prepared by oxidation-triggered polymerization of green tea catechins in impacting these effects in [...] Read more.
Repeated exposure to tobacco smoke causes neuroinflammation and neuroplasticity, which correlates with smoking withdrawal-induced anxiety. The purpose of this study was to investigate the anticipated involvement of antioxidant-rich nanoparticles (NPs) prepared by oxidation-triggered polymerization of green tea catechins in impacting these effects in a rat model of tobacco smoke exposure. Exposure to tobacco smoke was carried out for 2 h a day, 5 days a week, for a total of 36 days. Weekly behavioral tests were conducted prior to recommencing the exposure. Following a 20-day exposure period, rats were administered either distilled water or green tea (GT) NPs (20 mg/kg, orally) for an additional 16 days. Our findings revealed that tobacco smoke exposure induced anxiety-like behavior indicative of withdrawal, and this effect was alleviated by GT NPs. Tobacco smoke exposure caused a marked increase in the relative mRNA and protein expression of nuclear factor-kappa B (NF-κB) and reduced the relative mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and hypothalamus (HYP) brain subregions. The intervention of GT NPs effectively inhibited these effects. Our findings demonstrate the potent protective role of GT NPs in reducing withdrawal-induced anxiety-like behavior, neuroinflammation, and neuroplasticity triggered by tobacco smoke exposure. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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24 pages, 3219 KiB  
Article
Predictors of Serotonin Syndrome in Acute Poisoning with 5-Hydroxytryptamine Modulators
by Asmaa F. Sharif, Mubarak Nasir M. Almulhim, Hadi Mohamed A. Almosabeh, Mohammed Essam A. Alshammasy, Ali Mohammed A. Aljeshi, Taher Mohammed A. Mufti, Shahd AlNasser, Khalid A. Al-Mulhim and Yousef A. AlMubarak
Toxics 2024, 12(8), 550; https://doi.org/10.3390/toxics12080550 - 30 Jul 2024
Viewed by 1498
Abstract
5-Hydroxytryptamine (5-HT) modulators are commonly prescribed medications with potentially life-threatening outcomes, particularly serotonin syndrome (SS). Early prediction of SS is critical not only to avoid lethal drug combinations but also to initiate appropriate treatment. The present work aimed to recognize the significant predictors [...] Read more.
5-Hydroxytryptamine (5-HT) modulators are commonly prescribed medications with potentially life-threatening outcomes, particularly serotonin syndrome (SS). Early prediction of SS is critical not only to avoid lethal drug combinations but also to initiate appropriate treatment. The present work aimed to recognize the significant predictors of SS through a retrospective cross-sectional study that was conducted among patients exposed to an overdose of 5-HT modulators and admitted to a poison control center where 112 patients were enrolled. Of them, 21 patients were diagnosed with SS, and 66.7% of patients with SS were exposed to long-term co-ingestion. There was a noticeable surge in SS between April and May, and 52.4% of patients who suffered from SS were admitted after suicidal exposure (p < 0.05). Patients with SS showed severe presentation indicated by high-grade poison severity scores (PSS) and low Glasgow coma scales (GCS). PSS was a significant predictor of SS with an area under the curve of 0.879. PCO2, pulse, GCS, HCO3, and erythrocytic count were other significant predictors of SS. Combinations of serotonergic agents increase the likelihood of developing SS. Clinicians should be vigilant when prescribing a combination of serotonergic therapy, particularly for patients on illicit sympathomimetic and over-the-counter medications like dextromethorphan. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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Review

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44 pages, 551 KiB  
Review
The Dark Side of “Smart Drugs”: Cognitive Enhancement vs. Clinical Concerns
by Mariarosaria Ingegneri, Erika Smeriglio, Younes Zebbiche, Laura Cornara, Letterio Visalli, Antonella Smeriglio and Domenico Trombetta
Toxics 2025, 13(4), 247; https://doi.org/10.3390/toxics13040247 - 26 Mar 2025
Viewed by 842
Abstract
The European Union Drugs Agency has emphasized the increasing difficulty in monitoring the drug market due to the emergence of new psychoactive substances, often marketed as legal highs. The proliferation of fake pharmacies, drugstores, and e-commerce platforms has made access to illicit substances [...] Read more.
The European Union Drugs Agency has emphasized the increasing difficulty in monitoring the drug market due to the emergence of new psychoactive substances, often marketed as legal highs. The proliferation of fake pharmacies, drugstores, and e-commerce platforms has made access to illicit substances alarmingly rapid and inexpensive. These substances are readily available without medical prescriptions, lacking proper risk assessments or monitoring of potential adverse effects, raising significant public health concerns. Today, the relentless pursuit of validation and success—often, at any cost—has led to an exponential rise in the use of cognitive and mood enhancers. Such substances are frequently consumed to manage demands related to work, diet, sexuality, sleep, achievement, and interpersonal relationships. Consequently, investigating these phenomena is critically important for institutions, as they represent a serious threat to individual development and health. Developing effective preventive and protective systems is essential. This review provides an overview of currently available smart drugs, discussing their desired and adverse neuropharmacological effects, psychological implications, and cognitive decline resulting from their excessive and unregulated use. This review concludes that a multidisciplinary approach combining molecular identification, micro-morphological analysis, and chemical characterization is crucial for the accurate detection, monitoring, and risk mitigation of new psychoactive substances. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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