Academic Journal
Cannabidiol attenuates methamphetamine-induced psychosis via anti-oxidative stress: σ1R-mediated mitochondrial dysfunction as a critical pathway.
| Τίτλος: | Cannabidiol attenuates methamphetamine-induced psychosis via anti-oxidative stress: σ1R-mediated mitochondrial dysfunction as a critical pathway. |
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| Συγγραφείς: | Liu L; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, PR China., Wang C; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, PR China., Tian Y; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, PR China., Yin Y; Department of Laboratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, PR China., Rao M; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, PR China., Tao H; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, PR China., Luo C; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, PR China., Li J; Department of Pathogen Biology and Immunology, School of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, PR China.. Electronic address: 121093258@qq.com., Zeng X; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, PR China.. Electronic address: zxf2004033@163.com. |
| Πηγή: | Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2026 May; Vol. 154, pp. 158015. Date of Electronic Publication: 2026 Feb 26. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Urban & Fischer Verlag Country of Publication: Germany NLM ID: 9438794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-095X (Electronic) Linking ISSN: 09447113 NLM ISO Abbreviation: Phytomedicine Subsets: MEDLINE |
| Imprint Name(s): | Publication: Stuttgart : Urban & Fischer Verlag Original Publication: Stuttgart ; New York : G. Fischer, c1994- |
| Ιατρικοί όροι (MeSH): | Receptors, sigma*/metabolism , Oxidative Stress*/drug effects , Cannabidiol*/pharmacology , Cannabidiol*/therapeutic use , Mitochondria*/drug effects , Mitochondria*/metabolism , Methamphetamine*/adverse effects , Antioxidants*/pharmacology , Psychoses, Substance-Induced*/drug therapy , Psychoses, Substance-Induced*/metabolism, Hippocampus/drug effects ; Hippocampus/metabolism ; Neuroprotective Agents/pharmacology ; Calcium/metabolism ; Anxiety/drug therapy ; Anxiety/chemically induced ; Animals ; Sigma-1 Receptor ; Male ; Mice ; Mice, Inbred C57BL |
| Περίληψη: | Background: Methamphetamine-induced psychosis (MIP) occurs in 26-46% of chronic METH users, yet its pathogenesis and effective treatments remain unclear. Cannabidiol (CBD), a neuroprotective phytocannabinoid, exhibits antioxidant effects and has shown therapeutic potential in neuropsychiatric disorders. Purpose: This study aimed to elucidate CBD's therapeutic mechanisms against MIP, focusing on Sigma-1 receptor (σ1R)-mediated mitochondrial dysfunction. Methods: We employed in vitro and in vivo METH-exposure models. MIP-related behaviors were assessed using the open field, elevated plus maze, novel object recognition, Y-maze, and Morris water maze tests. Network pharmacology was used to identify CBD targets associated with MIP. Molecular analyses included assessments of neuronal morphology, oxidative stress markers, mitochondrial superoxide, and Ca²⁺ levels in the mouse hippocampus and HT22 cells. To modulate σ1R function, genetic knockout or overexpression strategies were employed. The interaction between CBD and σ1R was investigated using molecular dynamics simulations and surface plasmon resonance (SPR). Results: We found that CBD (40 mg/kg) alleviated METH-induced anxiety-like behaviors and cognitive deficits in mice. Network pharmacology revealed that CBD alleviated MIP through anti-oxidative stress. CBD also reduced neuronal damage, mitochondrial superoxide production, membrane potential loss, and Ca²⁺ dysregulation in the mouse hippocampus and HT22 cells. Mechanistically, the neuroprotective effects of CBD were recapitulated by σ1R knockout or inhibition and diminished by its overexpression; this functional link was supported by molecular dynamics simulations and SPR assays, which confirmed stable CBD-σ1R binding. Conclusion: CBD alleviates METH-induced anxiety-like behaviors, cognitive impairments, and hippocampal neuronal damage in mice by attenuating σ1R-mediated mitochondrial oxidative stress and Ca²⁺ overload. (Copyright © 2026 Elsevier GmbH. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cannabidiol; Methamphetamine; Mitochondrial dysfunction; Oxidative stress; Psychosis; Sigma-1 receptor |
| Substance Nomenclature: | 0 (Receptors, sigma) 0 (Sigma-1 Receptor) 19GBJ60SN5 (Cannabidiol) 44RAL3456C (Methamphetamine) 0 (Antioxidants) 0 (Neuroprotective Agents) SY7Q814VUP (Calcium) |
| Entry Date(s): | Date Created: 20260308 Date Completed: 20260710 Latest Revision: 20260710 |
| Update Code: | 20260711 |
| DOI: | 10.1016/j.phymed.2026.158015 |
| PMID: | 41795471 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1618-095X |
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| DOI: | 10.1016/j.phymed.2026.158015 |