Saturday, March 13, 2010

April 2010: Cannabinoids inhibit highly invasive cancer metastasis. (University of Rostock; Rostock, Germany)

Note: April refers to publication date, which is April 1; the actual study was conducted in November 2009. Additionally, to all the avid readers, I apologize for the wait, it's been a busy couple of weeks.

First some background: Most of the research summaries featured within this blog involve the effects of synthetic cannabinoid receptor agonists rather than the actual substances found within plants of the Cannabis genus. Although the ∆9-Tetrahydrocannabinol (THC) found in Cannabis is a CB1 and CB2 cannabinoid receptor agonist, it is still rarely used experimentally. Rarer still, is experimentation with one of the several other cannabinoids found within Cannabis plants. There are four other known cannabinoids that have been derived from Cannabis: Cannabidiol (CBD), Cannabinol (CBN), Tetrahydrocannabivarin (THCV), and Cannabichromene (CBC). When a patient considers the alternatives to medical marijuana, there is only one that supposedly is comparable, Dronabinol, marketed by Abbott (formally Solvay) pharmaceuticals as Marinol. Dronabinol is essentially synthetically produced THC, and thus contains only one of the substances in Cannabis that has shown therapeutic potential. Additionally, not all cannabinoids found in Cannabis act on the primary cannabis receptors CB1 and CB2; therefore in order to achieve the full medical benefits of marijuana, the other substances must be consumed as well. One of the other cannabinoids found in Cannabis plants is cannabidiol. Although it has not been researched as extensively as THC, it has been shown to generally make up 40% of extracts from the Cannabis plant.1 Cannabidiol’s exact physiological functions have not been fully understood, but it has been previously shown to interact with TRPV1 (transient receptor potential cation channel, subfamily V, member 1) receptors and have anti-cancer properties.

The new information: In this experiment, two different cancer cell lines were treated with cannabidiol, and both showed impaired invasion. The cell lines were of highly invasive human cervical cancer (HeLa, C33A) and human lung cancer (A549). The cannabidiol-driven impaired invasion was shown to be reversed by both an antagonist to CB1 and CB2 cannabinoid receptors as well as an antagonist to TRPV1 receptors. Although this did not represent particularly novel information, it was also found that the decrease in invasion occurred concurrently with an increase in TIMP-1 (tissue inhibitor of matrix metalloprotease-1). When the cell lines were genetically altered to be unable to produce TIMP-1, cannabidiol showed no effect in impairing cancer invasion. Additionally, the human lung cancer cell line was induced in thymic-aplastic nude mice, which lack a functioning immune system that could possibly defend against the cancer, where it was found that treatment with cannabidiol caused significant inhibition of lung metastasis.

What this means: The results of this study indicate that current pharmaceutical capabilities to utilize the substances found in the Cannabis plant are severely underdeveloped. In order to utilize the full therapeutic potential of marijuana, it must be ingested along with other substances naturally occurring in the plant. This particular experiment elucidated the molecular mechanism of cannabidiol-induced inhibition of cancer metastasis, which along with studies pertaining to anti-cancer effects of strictly cannabinoid receptor agonists, start to form a complete picture of the cancer-inhibiting capabilities of Cannabis.

1Grlie, L. "A Comparative Study on Chemical and Biological Characteristics of Various Samples of Cannabis Resin." Bulletin on Narcotics. 14(1976): 37–46.

Ramer, R., et al. “Cannabidiol Inhibits Cancer Cell Invasion via Upregulation of Tissue Inhibitor of Matrix Metalloproteinases-1.” Biochemical Pharmacology. 79.7(2010): 955-66.

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