Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)

ABSTRACT Glioma is the most common and lethal primary brain tumor in adults, with glioblastoma (GBM) representing the most aggressive subtype, characterized by diffuse infiltration, resistance to therapy, and a poor prognosis. Despite standard treatments, survival remains only approximately 14 month...

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Main Authors: Farideh A. Javid, Andrej Belancic, Man Ki Kwok, Yun Wah Lam
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Pharmacology Research & Perspectives
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Online Access:https://doi.org/10.1002/prp2.70160
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author Farideh A. Javid
Andrej Belancic
Man Ki Kwok
Yun Wah Lam
author_facet Farideh A. Javid
Andrej Belancic
Man Ki Kwok
Yun Wah Lam
author_sort Farideh A. Javid
collection DOAJ
description ABSTRACT Glioma is the most common and lethal primary brain tumor in adults, with glioblastoma (GBM) representing the most aggressive subtype, characterized by diffuse infiltration, resistance to therapy, and a poor prognosis. Despite standard treatments, survival remains only approximately 14 months. Cannabinoids have been increasingly investigated for their therapeutic potential in gliomas, particularly GBM. Although multiple reviews on this field of research have been published, most are current only up to 2022. This systematic review aims to provide an updated summary of studies published between 2022 and 2025, capturing recent developments in anti‐glioma mechanisms, combinational strategies, immune modulation, and novel therapeutic platforms. Following PRISMA guidelines, PubMed, Scopus, ScienceDirect, and SpringerLink were searched for original English‐language journal articles published between January 2022 and February 2025, using search terms related to cannabinoids and brain cancer. From 1031 records, 45 original research articles were included after removing duplicates, non‐primary studies, and irrelevant topics. The studies were categorized into seven thematic domains based on content. Recent studies have elaborated on the anti‐cancer mechanisms of cannabinoids beyond endocannabinoid signaling via the CB1/CB2 receptor, including ferroptosis induction, mitochondrial dysfunction, integrated stress response activation, and epigenetic modulation. Synthetic cannabinoids and their analogs demonstrated enhanced blood–brain barrier penetration and cytotoxicity in glioma models. Cannabinoids have been shown to modulate immune responses in glioma, influencing T cell infiltration, myeloid suppressor cell recruitment, and tumor‐associated macrophage function. Novel formulation and delivery strategies have improved cannabinoid solubility, stability, and tumor targeting. Combination therapies, particularly cannabidiol with temozolomide or radiotherapy, exhibited additive or synergistic anti‐tumor effects, although variability between glioma subtypes suggests the need for personalized approaches. Although cannabinoid‐based glioma research has expanded our understanding of the mechanisms, discrepancies between preclinical findings and clinical data highlight the need for rigorous clinical trials and mechanistic research before cannabinoid‐based treatments can be reliably integrated into standard glioma care.
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spelling doaj-art-4d302abc429f4a0f93bb178822aaa9552025-08-20T03:36:26ZengWileyPharmacology Research & Perspectives2052-17072025-08-01134n/an/a10.1002/prp2.70160Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)Farideh A. Javid0Andrej Belancic1Man Ki Kwok2Yun Wah Lam3Department of Pharmacy School of Applied Sciences, University of Huddersfield Huddersfield UKDepartment of Basic and Clinical Pharmacology With Toxicology, Faculty of Medicine University of Rijeka Rijeka CroatiaDepartment of Health Sciences School of Nursing and Health Sciences, Hong Kong Metropolitan University Hong Kong SAR ChinaDepartment of Health Sciences School of Nursing and Health Sciences, Hong Kong Metropolitan University Hong Kong SAR ChinaABSTRACT Glioma is the most common and lethal primary brain tumor in adults, with glioblastoma (GBM) representing the most aggressive subtype, characterized by diffuse infiltration, resistance to therapy, and a poor prognosis. Despite standard treatments, survival remains only approximately 14 months. Cannabinoids have been increasingly investigated for their therapeutic potential in gliomas, particularly GBM. Although multiple reviews on this field of research have been published, most are current only up to 2022. This systematic review aims to provide an updated summary of studies published between 2022 and 2025, capturing recent developments in anti‐glioma mechanisms, combinational strategies, immune modulation, and novel therapeutic platforms. Following PRISMA guidelines, PubMed, Scopus, ScienceDirect, and SpringerLink were searched for original English‐language journal articles published between January 2022 and February 2025, using search terms related to cannabinoids and brain cancer. From 1031 records, 45 original research articles were included after removing duplicates, non‐primary studies, and irrelevant topics. The studies were categorized into seven thematic domains based on content. Recent studies have elaborated on the anti‐cancer mechanisms of cannabinoids beyond endocannabinoid signaling via the CB1/CB2 receptor, including ferroptosis induction, mitochondrial dysfunction, integrated stress response activation, and epigenetic modulation. Synthetic cannabinoids and their analogs demonstrated enhanced blood–brain barrier penetration and cytotoxicity in glioma models. Cannabinoids have been shown to modulate immune responses in glioma, influencing T cell infiltration, myeloid suppressor cell recruitment, and tumor‐associated macrophage function. Novel formulation and delivery strategies have improved cannabinoid solubility, stability, and tumor targeting. Combination therapies, particularly cannabidiol with temozolomide or radiotherapy, exhibited additive or synergistic anti‐tumor effects, although variability between glioma subtypes suggests the need for personalized approaches. Although cannabinoid‐based glioma research has expanded our understanding of the mechanisms, discrepancies between preclinical findings and clinical data highlight the need for rigorous clinical trials and mechanistic research before cannabinoid‐based treatments can be reliably integrated into standard glioma care.https://doi.org/10.1002/prp2.70160cannabinoid therapeuticsendocannabinoid signalingglioblastomagliomasystematic review
spellingShingle Farideh A. Javid
Andrej Belancic
Man Ki Kwok
Yun Wah Lam
Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)
Pharmacology Research & Perspectives
cannabinoid therapeutics
endocannabinoid signaling
glioblastoma
glioma
systematic review
title Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)
title_full Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)
title_fullStr Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)
title_full_unstemmed Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)
title_short Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022–2025)
title_sort recent advances in the therapeutic potential of cannabinoids against gliomas a systematic review 2022 2025
topic cannabinoid therapeutics
endocannabinoid signaling
glioblastoma
glioma
systematic review
url https://doi.org/10.1002/prp2.70160
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