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Cannabinoids in the treatment of glioblastoma

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Abstract

Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous system. While the treatment of other neoplasms is increasingly more efficacious the median survival rate of GBM patients remains low and equals about 14 months. Due to this fact, there are intensive efforts to find drugs that would help combat GBM. Nowadays cannabinoids are becoming more and more important in the field of cancer and not only because of their properties of antiemetic drugs during chemotherapy. These compounds may have a direct cytotoxic effect on cancer cells. Studies indicate GBM has disturbances in the endocannabinoid system—changes in cannabinoid metabolism as well as in the cannabinoid receptor expression. The GBM cells show expression of cannabinoid receptors 1 and 2 (CB1R and CB2R), which mediate various actions of cannabinoids. Through these receptors, cannabinoids inhibit the proliferation and invasion of GBM cells, along with changing their morphology. Cannabinoids also induce an intrinsic pathway of apoptosis in the tumor. Hence the use of cannabinoids in the treatment of GBM may be beneficial to the patients. So far, studies focusing on using cannabinoids in GBM therapy are mainly preclinical and involve cell lines and mice. The results are promising and show cannabinoids inhibit GBM growth. Several clinical studies are also being carried out. The preliminary results show good tolerance of cannabinoids and prolonged survival after administration of these drugs. In this review, we describe the impact of cannabinoids on GBM and glioma cells in vitro and in animal studies. We also provide overview of clinical trials on using cannabinoids in the treatment of GBM.

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Authors and Affiliations

  1. Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, Warsaw, 02097, Poland

    Barbara Buchalska, Katarzyna Kamińska, Maja Owe-Larsson & Agnieszka Cudnoch-Jędrzejewska

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  1. Barbara Buchalska
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  2. Katarzyna Kamińska
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BB created the concept of the article. BB performed the literature search, and data analysis, and drafted the manuscript. BB and MOL created the figures. KK and ACJ critically revised the work and prepared the final version of the manuscript. All authors accepted the final version of the manuscript.

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Correspondence to Katarzyna Kamińska.

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List of abbreviations

ADC—apparent diffusion coefficient.

AEA—anandamide.

2-AG—2-arachidonoyl glycerol.

Aml-1—acute myeloid leukemia 1.

AMPK—5’AMP-activated protein kinase.

ATP—adenosine triphosphate.

BBB—blood-brain barrier.

Bcl-2—B-cell lymphoma 2 family.

C. sativa—Cannabis sativa.

cAMP—cyclic adenosine monophosphate.

CB1R—cannabinoid 1 receptor.

CB2R—cannabinoid 2 receptor.

CBGs—cannabigerols.

CBCs—cannabichromenes.

CBDs—cannabidiols.

CBEs—cannabielsoins.

CBLs—cannabicyclols.

CBNs—cannabinols.

CBNDs—cannabinodiols.

CBTs—cannabitriols.

CD103—cluster of differentiation 103.

CNR1—CB1R gene.

CNR2—CB2R gene.

COX2—cytochrome c oxidase subunit 2.

COX4—cytochrome c oxidase subunit 4.

CYP—cytochrome P450.

DGL—diacylglycerol lipase-alpha.

DWI—diffusion-weighted imaging.

eCBs—endocannabinoids.

EGFR—epidermal growth factor receptor.

EVs—extracellular vesicles.

E2F1—E2F transcription factor 1.

FAAH—fatty acid amide hydrolase.

FAK—focal adhesion kinase.

pFAK—phosphorylated FAK.

FOXM1—forkhead box M1.

GABA—gamma-aminobutyric acid.

GBM—glioblastoma.

GFAP—glial fibrillary acidic protein.

GPCRs—G-protein coupled receptors.

GPR55—G protein-coupled receptor 55.

GRKs—G-protein receptor kinases.

GSCs—glioma stem cells.

GSH—glutathione.

HGGs—high-grade gliomas.

HSPs—heat shock proteins.

IC50—half maximal inhibitory concentration.

Id1—inhibitor of DNA binding 1.

IDO—indoleamine 2,3-dioxygenase.

IL-8—interleukin 8.

LC3-I—light chain 3.

LGG—low grade glioma.

MAPK—p44/42 mitogen-activated protein kinase.

MGL—monoacylglycerol lipase.

MMP-2—matrix metalloproteinase-2.

MRI—magnetic resonance imaging.

mTORC1—mechanistic target of rapamycin complex 1.

NAPE-PLD—N-acylphosphatidylethanolamine-hydrolysing phospholipase D.

NDUFA9—NADH dehydrogenase 1 alpha subcomplex subunit 9.

NDUFB8—NADH dehydrogenase 1 beta subcomplex subunit 8.

NF-kB—nuclear factor kappa-light-chain-enhancer of activated B cells.

NK-1—neurokinin 1.

NRF2—nuclear factor erythroid 2-related factor 2.

p53—cellular tumor antigen p53.

p-STAT3—signal transducer and activator of transcription 3.

PTEN—phosphatase and tensin homolog gene.

Rb—retinoblastoma protein.

RELA—v-rel reticuloendotheliosis viral oncogene homolog A.

ROS—reactive oxygen species.

RTKs—receptor tyrosine kinases.

SCs—synthetic cannabinoids.

Sox2—sex determining region Y box 2.

Δ8-THCs—Δ8-trans-tetrahydrocannabinols.

Δ9-THCs, THCs—Δ9-trans-tetrahydrocannabinols.

TME—tumor microenvironment.

TMZ—temozolomide.

TP53—p53 protein gene.

TRPA—transient receptor potential ankyrin.

TRPM—transient receptor potential melastatin.

TRPV1—transient receptor potential cation channel subfamily V member 1.

TRPV2—transient receptor potential cation channel subfamily V member 2.

TRPV4—transient receptor potential cation channel subfamily V member 4.

VEGFR-2—vascular endothelial growth factor receptor 2.

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Buchalska, B., Kamińska, K., Owe-Larsson, M. et al. Cannabinoids in the treatment of glioblastoma. Pharmacol. Rep 76, 223–234 (2024). https://doi.org/10.1007/s43440-024-00580-x

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