Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: The prevalence of methamphetamine (METH) abuse has significantly escalated in many regions worldwide. Despite this increase, the complexity of neurotoxicity associated with METH is inadequately understood. Cannabidiol (CBD), a non-addictive plant ingredient in cannabis, has been used in preclinical and clinical studies for treating various neuropsychiatric disorders, but the mechanism by which CBD exerts therapeutic effects is still unclear.
Purpose: This work aims to explore the mechanism of transient receptor potential vanilloid type 1 (TRPV1) mediates oxidative neurotoxicity in the context of METH exposure and reveal the therapeutic target of CBD for METH-induced oxidative neurotoxicity.
Results: In the hippocampus and medial prefrontal cortex of METH users, overactivation of TRPV1, intracellular Ca overload, increased oxidative stress, and elevated apoptosis were observed compared to control individuals. Molecular docking and surface plasmon resonance (SPR) detection results indicated that CBD binds to human TRPV1. In addition, METH induced Ca influx, oxidative stress, cell damage, and TRPV1 activation in HT-22 cells, which were mitigated by TRPV1 knockdown or CBD pretreatment. CBD pretreatment also blocked TRPV1 agonist capsaicin-induced Ca influx, oxidative stress, cell damage, and TRPV1 activation in HT-22 cells. Furthermore, METH triggered stereotyped behavior, spatial memory impairment, TRPV1 activation, Ca overload, apoptosis, and oxidative stress in the hippocampus, which were attenuated by CBD pretreatment in mice. Finally, hippocampal TRPV1 knockdown reduced METH-induced stereotyped behavior and spatial memory impairment in mice, blocked METH-induced apoptosis and oxidative stress in the hippocampus of mice.
Conclusion: METH induces oxidative neurotoxicity via activating TRPV1-dependent Ca influx, oxidative stress, and apoptosis, while CBD inhibits METH-induced oxidative neurotoxicity by regulating TRPV1. This study establishes CBD as a therapeutic intervention for METH use disorders.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.phymed.2025.157015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Guishen-erxian Decoction can improve ovarian function in rats with premature ovarian failure by inhibiting oxidative stress and granulosa cell DNA fragmentation mediated by the PI3K/Akt/FOXO3a pathway.
Histol Histopathol
September 2025
Center for Experimental Teaching, School of Pharmacy, Guangzhou Medical University, Guangzhou, China.
Background: The aim of this study was to establish a rat model of premature ovarian failure (POF) with cyclophosphamide (CTX), and explore the molecular basis of POF and the mechanism of Guishen-Erxian Decoction (GSEXD) to improve POF from the perspective of oxidative stress regulation of ovarian granulosa cell (OGC) DNA fragmentation.
Method: The study utilized SD rats to establish a POF model via CTX. Rats were divided into Control, POF group, three GSEXD dosage groups (low, medium, high), and a GSEXD+PI3K agonist group to assess GSEXD's therapeutic effects on oxidative stress, DNA fragmentation and ovarian damage.
SIRT3-FOXO3a Isoforms Forge Nuclear-Mitochondrial Links to Combat Sepsis-Induced Cardiomyopathy Oxidative Stress in Mice.
Antioxid Redox Signal
September 2025
Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Sepsis-induced cardiomyopathy (SIC) is a serious complication of sepsis. The relationship between SIC and protein acetylation, particularly the balance between acetylation and deacetylation in cardiomyocyte subcellular structures, as well as how nuclear-mitochondrial coordination maintains standard antioxidant stress capacity, remains unclear. This study focused on exploring the nuclear-mitochondrial regulatory mechanisms formed by the interplay of Sirtuin 3 (SIRT3) and Forkhead box O3a (FOXO3a).
View Article and Find Full Text PDFConcussive injuries induce neuronal stress-dependent tau mislocalization to dendritic spines with acrolein and functional network alteration in TBI-on-a-chip.
Lab Chip
September 2025
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Traumatic brain injuries (TBIs) are a risk factor for Alzheimer's disease (AD), and share several important pathological features including the development of neurofibrillary tangles (NFT) of tau protein. While this association is well established, the underlying pathogenesis is poorly defined and current treatment options remain limited, necessitating novel methods and approaches. In response we developed "TBI-on-a-chip", an trauma model utilizing murine cortical networks on microelectrode arrays (MEAs), capable of reproducing clinically relevant impact injuries while providing simultaneous morphological and electrophysiological readout.
View Article and Find Full Text PDFType-I Supramolecular Photosensitizer Enables GSH Depletion by Hydrogen Atom Transfer.
J Am Chem Soc
September 2025
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Photodynamic therapy (PDT) induces oxidative stress that triggers a compensatory upregulation of intracellular glutathione (GSH), thereby diminishing PDT efficacy. The simultaneous generation of reactive oxygen species and depletion of GSH holds promise for amplifying oxidative damage and enhancing therapeutic outcomes yet remains a challenge. In this work, we present a Type-I supramolecular photosensitizer designed to deplete GSH through a hydrogen atom transfer mechanism while concurrently generating superoxide radicals.
View Article and Find Full Text PDFMitochondrial ClpX Inhibition Induces Ferroptosis and Blocks Pancreatic Cancer Cell Proliferation.
Chembiochem
September 2025
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, P. R. China.
The ATPase caseinolytic protease X (ClpX), forming the ClpXP complex with caseinolytic protease P (ClpP), is essential for mitochondrial protein homeostasis. While ClpP targeting is a recognized anticancer strategy, the role of ClpX in cancer remains underexplored. In pancreatic ductal adenocarcinoma (PDAC), elevated CLPX expression correlates with poor prognosis, suggesting its oncogenic function.
View Article and Find Full Text PDF