5‐Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non‐psychoactive cannabinoid

  title={5‐Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non‐psychoactive cannabinoid},
  author={Paola Massi and Marta Valenti and Angelo Vaccani and Valeria Gasperi and Gianpaolo Perletti and Emanuela Marras and Filomena Fezza and Mauro Maccarrone and Daniela Parolaro},
  journal={Journal of Neurochemistry},
It has been recently reported that cannabidiol (CBD), a non‐psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation. However, the underlying biochemical mechanisms were not clarified. In the present study, we performed biochemical analysis of the effect of CBD both in vivo, by using glioma tumor tissues excised from nude mice, and in vitro, by using U87 glioma cells. In vivo exposure of tumor tissues to CBD… 

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids

Mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells are discussed.

Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival

Cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Δ9-THC is tested and it is suggested that the addition of cannabidiole may improve the overall effectiveness of Δ9 -THC in the treatment of glioblastoma in cancer patients.

Cannabidiol as potential anticancer drug

The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents.

Endocannabinoid system and the expression of endogenous ceramides in human hepatocellular carcinoma.

Evaluating the expression patterns of endocannabinoids and endogenous ceramides in 67 pairs of human hepatocellular carcinoma (HCC) tissues and non-cancerous counterpart controls found that cannabinoid receptor 1 was downregulated, while cannabinoid receptor 2 was elevated in HCC tissues, in accordance with the alterations in the levels of AEA and 2-AG.

COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells

In lung cancer cell lines and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis and caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662.

Cannabinoid receptor ligands as potential anticancer agents--high hopes for new therapies?

This review critically discusses the pharmacology of CB receptor activation as a novel therapeutic anticancer strategy in terms of ligand selectivity, tissue specificity and potency.

FABP1 controls hepatic transport and biotransformation of Δ9-THC

Test the central hypothesis that liver-type fatty acid binding protein (FABP1) mediates phytocannabinoid transport and subsequent inactivation and position FABP 1 as a hepatic THC transport protein and a critical mediator of cannabinoid inactivation.

Cannabidiol, a Non-Psychoactive Cannabinoid Compound, Inhibits Proliferation and Invasion in U87-MG and T98G Glioma Cells through a Multitarget Effect

The results support CBD exploitation as an effective anti-cancer drug in the management of gliomas and show that this cannabinoid affects multiple tumoral features and molecular pathways.

Anti‐tumour actions of cannabinoids

Results emerging from preclinical studies suggest cannabinoids elicit effects at different levels of cancer progression, including inhibition of proliferation, neovascularization, invasion and chemoresistance, induction of apoptosis and autophagy as well as enhancement of tumour immune surveillance.



Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines

Evaluating the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines suggests a possible application of CBD as an antineoplastic agent.

The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: a possible role for cyclooxygenase 2

Findings suggest anandamide may be a useful chemopreventive/therapeutic agent for colorectal cancer as it targets cells that are high expressors of COX-2, and may also be used in the eradication of tumour cells that have become resistant to apoptosis.

New insights into endocannabinoid degradation and its therapeutic potential.

Growing evidence that demonstrates that these hydrolases are pivotal regulators of the endogenous levels of AEA and 2-AG in vivo are reviewed, overall suggesting that specific inhibitors of AMT, FAAH or MAGL may serve as attractive therapeutic targets for the treatment of human disorders.

Inhibition of tumor angiogenesis by cannabinoids

It is shown that local administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of malignant gliomas as determined by immunohistochemical analyses and vascular permeability assays.

The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

A different sensitivity to the anti-proliferative effect of CBD is found in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.

Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non‐tumour brain tissue

The enhanced level of the 2‐arachidonoyl glycerol, anandamide and other N‐acylethanolamines detected in the two types of tumour tissue may possibly act as endogenous anti‐tumour mediators by stimulation of both cannabinoid and non‐cannabinoid receptor‐mediated mechanisms.

Inhibition of rat C6 glioma cell proliferation by endogenous and synthetic cannabinoids. Relative involvement of cannabinoid and vanilloid receptors.

The antiproliferative effects of the endocannabinoids upon C6 cells are brought about by a mechanism involving combined activation of both vanilloid receptors and to a lesser extent cannabinoid receptors, and leading to oxidative stress and calpain activation.

Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of p22phox and Nox4 Expression

The results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22phox expression, may be a novel and highly selective treatment for leukemia.

Low doses of anandamides inhibit pharmacological effects of delta 9-tetrahydrocannabinol.

  • E. FrideJ. Barg Z. Vogel
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1995
It is suggested that the inhibition of delta 9-THC-induced effects by low doses of anandamides may be due to partial agonistic effects of these materials, or may cause an allosteric modulation of the cannabinoid receptor.