Cannabidiol enhances the inhibitory effects of Delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival.

Cannabis Contains Compounds That Inhibit Cancer

Marcu JP, Christian RT, Lau D, Zielinski AJ, Horowitz MP, Lee J, Pakdel A, Allison J, Limbad C, Moore DH, Yount GL, Desprez PY, McAllister SD

Summary:

California Pacific Medical Center Research Institute, San Francisco, California 94107, USA.

The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB(1) and CB(2) receptors, can modulate the actions of Delta(9)-THC. There are conflicting reports, however, as to what extent other cannabinoids can modulate Delta(9)-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Delta(9)-THC. We therefore tested cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Delta(9)-THC. In the U251 and SF126 glioblastoma cell lines, Delta(9)-THC and cannabidiol acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of cannabidiol to Delta(9)-THC may improve the overall effectiveness of Delta(9)-THC in the treatment of glioblastoma in cancer patients.

PMID: 20053780 [PubMed - in process]

San Francisco, CA: Marijuana's active compounds act synergistically to inhibit the growth of cancer cells and induce malignant cell death, according to preclinical trial data published online by the journal Molecular Cancer Therapeutics.

Investigators at the University of California, Pacific Medical Center Research Institute assessed whether the administration of the non-psychoactive cannabidiol would enhance the anti-cancer effects of THC on glioblastoma (brain cancer) cells.

Researchers reported that a combination of cannabinoids showed greater anti-cancer activity than the administration of either compound individually. "We discovered that cannabidiol enhanced the ability of THC to inhibit cell proliferation and induce cell cycle arrest and apoptosis (programmed cell death)," authors reported.

Investigators concluded: "Individually, THC and cannabidiol can activate distinct pathways in glioblastoma cells that ultimately culminate in inhibition of cancer cell growth and invasion as well as induction of cell death. We hypothesized that, if the individual agents were combined, a convergence on shared pathways may ensue, leading to an enhanced ability of the combination treatment to inhibit certain cancer cell phenotypes. We found this to be true in this investigation."

A 2008 scientific review published in the journal Cancer Research reported that the cannabinioids inhibit cell proliferation in a wide range of cancers, including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, and lymphoma.