Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity

Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity May 24, 2007. Sevda Dirikoc,1 Suzette A. Priola,2 Mathieu Marella,3 Nicole Zsürger,1 and Joëlle Chabry1. 1Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097, Centre National de la Recherche Scientifique, 06560 Valbonne, France, 2Laboratory of Persistent Viral Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, and 3Scripps Research Institute, La Jolla, California 92037

Correspondence should be addressed to Dr. Joëlle Chabry, Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097, Université de Nice-Sophia Antipolis, Centre National de la Recherche Scientifique, 660, route des lucioles, 06560 Valbonne, France. Email: chabry@ipmc.cnrs.fr

Prion diseases are transmissible neurodegenerative disorders characterized by the accumulation in the CNS of the protease-resistant prion protein (PrPres), a structurally misfolded isoform of its physiological counterpart PrPsen.

Both neuropathogenesis and prion infectivity are related to PrPres formation. Here, we report that the nonpsychoactive cannabis constituent cannabidiol (CBD) inhibited PrPres accumulation in both mouse and sheep scrapie-infected cells, whereas other structurally related cannabinoid analogs were either weak inhibitors or noninhibitory.

Moreover, after intraperitoneal infection with murine scrapie, peripheral injection of CBD limited cerebral accumulation of PrPres and significantly increased the survival time of infected mice.

Mechanistically, CBD did not appear to inhibit PrPres accumulation via direct interactions with PrP, destabilization of PrPres aggregates, or alteration of the expression level or subcellular localization of PrPsen.

However, CBD did inhibit the neurotoxic effects of PrPres and affected PrPres-induced microglial cell migration in a concentration-dependent manner.

Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection.

When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.

Key words: prion; cannabinoid; neuroprotection; scrapie-infected mice; cell-free conversion; microglia

------- Received Feb. 20, 2006; revised May 24, 2007; accepted June 13, 2007.

Please also read: Long Term Exposure To Cannabis

Ed Note: Yet another application for medicinal cannabis... (if we could only patent it ...) but you still can't have it because the DEA will hunt you down, courtesy of the American Pharmaceutical lobby and their employers; the American Pharmaceutical Industry.

*Industrial-Hemp has no psychoactive properties following definition of the European Economic Community (EEC); THC content is less than 0.3%. In general, low THC-seed varieties without psychoactive properties are those that have a THC content of less than 1%. (See also No-THC Hemp-seed.) THC= Delta-9 TetraHydroCannabinol.