Development of therapeutic strategies

Cannaprion

Use cannabinoids as anti-prion drugs

2007: 1 year / Grant: 15 000 euros

Project: In the absence of a relevant cure for Prion disorders, the aim of the project Cannaprion was to use non-psychoactive cannabinoid, the cannabidiol (CBD), to treat them. The rational was, that in addition to preventing prion accumulation and protecting neurons against prion toxicity, CBD possessed the properties to cross the blood brain barrier easily, to exibit weak toxicity and few side effects. These characteristics rendered them of great interest as potential anti-prion drugs.

Results and related published data: Cannabinoid intra-peritoneal treatment of scrapie infected mice significantly increased the survival time and limited prion accumulation. At the mechanistic level, cannabinoids could interfere with the different steps of the neurodegenerative process. To further understand the mechanism, the endocannabinoid system wasinvestigated in a prion-infected mouse model. The production of the endocannabinoid, 2-arachidonoyglycerol (2-AG) (but not the others), as well asthe CB2 receptor, were shown to be increased. As 2-AG was previously described to trigger the migration of microglial cells in a CB2-R dependant manner, and as the phenomenon could be antagonized by the non-psychoactive cannabidiol, these results could explain why CBD could protect against prion toxicity.

Alteration of the endocannabinoid system in mouse brain during prion disease. Petrosino S, Ménard B, Zsürger N, Di Marzo V, Chabry J. Neuroscience. 2011 Mar 17;177:292-7. doi: 10.1016/j.neuroscience.2010.12.046. Epub 2010 Dec 31.